A new study by UCLA researchers shows that administering the protein NELL-1
intravenously stimulates significant bone formation through the regenerative
ability of stem cells.
These preclinical results could one day have an impact on the development
of a treatment for osteoporosis, which affects more than 200 million people
worldwide, as well as potentially help those with traumatic bone injuries, such
as members of the military or even astronauts who lose bone density while in
space.
The study, published in the journal Nature Communications, was led by
co-senior authors Dr. Kang Ting, chair of orthodontics and the division of
growth and development in the UCLA School of Dentistry and Dr. Chia Soo,
professor and vice chair for research in the UCLA Division of Plastic and
Reconstructive Surgery in the David Geffen School of Medicine and member of the
UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell
Research.
"Our end goal is really to harness the bone forming properties of NELL-1 to
better treat patients with diverse causes of bone loss, from trauma in military
personnel to osteoporosis from age, disease or very weak gravity, which causes
bone loss in astronauts," said Ting, who discovered NELL-1 in 1996. Ting had
been studying children with craniosynostosis—a birth defect in which one or more
of the joints between the bones of a baby's skull close or fuse prematurely due
to overactive bone growth—and found that the NELL-1 protein was closely involved
in the overactive bone growth. This discovery presented scientists with the
opportunity to study the use of NELL-1 for the purpose of growing bone.
Bone is constantly being broken down and resorbed into the body and then
rebuilt in a process called bone remodeling. The two cell types in charge of
this process are osteoblasts (which build bone) and osteoclasts (which resorb—or
break down—bone). When osteoblasts and osteoclasts work in normal balance, bone
remodeling is a beneficial process. But, as people age, bone resorption
naturally outpaces bone formation, resulting in some loss of bone density. This
can be accelerated in some people due to factors including diet, lack of
exercise, genetics and habits such as smoking. Accelerated bone resorption by
osteoclasts results in osteoporosis, which makes bone brittle and prone to
fracture.
"For the millions of people living with osteopenia and osteoporosis, and
others with bone loss, the function of these cells is out of balance," said Soo,
who is also research director for UCLA Operation Mend, which provides medical
care for wounded military personnel. "We wanted to see how balance could be
restored through the use of NELL-1."
To investigate the use of NELL-1 in bone formation, the researchers started
by exposingadult stem cells that have the ability to create the bone-building
osteoblasts, known as mesenchymal stem cells, to NELL-1 in the laboratory. The
team found that mesenchymal stem cells exposed to NELL-1 in the laboratory
created osteoblasts that were much more effective at building bone.
Next, the researchers administered NELL-1 intravenously in animal models
and for the first time showed that NELL-1 could have this same effect on
mesenchymal stem cells within the body. Furthermore, the team found that NELL-1
reduces the ability of osteoclasts to resorb bone. The study showed that this
dual effect on both cell types significantly increased bonedensity.
"Our findings are exciting because they have big implications for possible
clinical application in the coming years," said the study's first author, Dr.
Aaron James, chief resident in anatomic pathology in the David Geffen School of
Medicine.
The NELL-1 method described above is used in preclinical tests only and has
not been tested in humans or approved by the Food and Drug Administration as
safe and effective for use in humans.
Read more:http://www.cusabio.com/catalog-13-1.html
2015年6月29日星期一
New family of small RNAs boosts cell proliferation in cancer
Since their discovery in the 1950s, transfer RNAs (tRNAs) have been best
known for their role in helping the cell make proteins from messenger RNA
templates. However, recent studies have led to a previously-unsuspected concept
that tRNAs are not always the end product; namely, they further serve as a
source of small RNAs. Now researchers have discovered a new species of
tRNA-derived small RNAs that are produced only in hormonally-driven breast and
prostate cancers, and which contribute to cell proliferation. The results will
be published online the week of June 29th in the Proceedings of the National
Academy of Sciences (PNAS).
"In early RNA sequencing studies, researchers observed an abundance of tRNA fragments in cellular transcriptome but those fragments had often been disregarded as non-functional degradation products," says Yohei Kirino, Ph.D., Assistant Professor in the Department of Biochemistry and Molecular Biology and a researcher at the Computational Medicine Center at Thomas Jefferson University. "This research is one of several recent studies that bring to light a new role for tRNAs to produce small functional RNAs, in this case, functional tRNA halves."
Although other tRNA halves have been described before -- specifically those that are produced during a cellular stress response -- this discovery represents a new and distinct species of tRNA halves that the authors coined SHOT-RNAs, for sex hormone dependent tRNA-derived RNAs.
Dr. Kirino and colleagues discovered these tRNA halves while looking at germline-specific small RNAs in the cells of a silkworm (Bombyx mori). In the cells, the researchers accidentally detected the tRNA halves whose expression was linked to cell proliferation. Since proliferation is a hallmark of cancer cells, the researchers analyzed the involvement of tRNA halves in tumorigenesis.
Using a new TaqMan PCR-based technique, the researchers screened a number of cancer cell lines from various tissues, and discovered that tRNA halves were specifically expressed in large quantities in sex hormone-dependent cancers, i.e., estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer that are driven by the hormones estrogen and testosterone. After confirming the dependency of the tRNA halves' expression on the hormones and their receptors, they coined the new tRNA halves, SHOT-RNAs.
SHOT-RNAs contain a terminal modification which prevents their detection by standard RNA-seq method. "The modification makes SHOT-RNAs invisible in RNA-seq data and this could be the reason why SHOT-RNAs had not been discovered in spite of their abundance and clear expression specificity in hormone-dependent cancers," says Dr. Kirino.
Dr. Kirino and colleagues created a novel method called cP-RNA-seq to comprehensively sequence SHOT-RNAs and found that only eight tRNA species produce SHOT-RNAs. They were also able to track the molecule's function in the cells, and tease apart the other cellular players it interacted with. They discovered, for example, that SHOT-RNAs are created by an enzyme called Angiogenin whose activity is promoted by sex hormone signaling pathways. They also showed that SHOT-RNAs are involved in spurring cell proliferation.
"The SHOT-RNAs are an exciting development in the tRNA field," said Isidore Rigoutsos, Ph.D., Director of the Computational Medicine Center at Thomas Jefferson University. "They are also another example of what appear to be regulators whose presence in a given tissue is modulated by a person's gender. Discovering such regulators is one of the major foci of the Computational Medicine Center."
In a final experiment, Dr. Kirino and colleagues also examined clinical samples from breast cancer patients and found elevated levels of SHOT-RNAs in patients with ER-positive luminal-type cancers, but not those that were negative for ER expression. The high expression specificity of SHOT-RNAs implies their potential use as a novel biomarker, and the next steps, says Dr. Kirino, are to explore relationships between SHOT-RNA expression and prognostic factors.
In spite of endocrine therapy to suppress hormone receptor activity or hormone exposure, many patients of hormone-dependent cancers encounter de novo or acquired resistance and require more aggressive treatments. Dr. Kirino says that "further studies to understand how SHOT-RNAs promote cell proliferation may lead to the use of SHOT-RNAs as potential target candidates for future therapeutic applications in breast and prostate cancers."
Read more:http://www.cusabio.com/catalog-15-1.html
"In early RNA sequencing studies, researchers observed an abundance of tRNA fragments in cellular transcriptome but those fragments had often been disregarded as non-functional degradation products," says Yohei Kirino, Ph.D., Assistant Professor in the Department of Biochemistry and Molecular Biology and a researcher at the Computational Medicine Center at Thomas Jefferson University. "This research is one of several recent studies that bring to light a new role for tRNAs to produce small functional RNAs, in this case, functional tRNA halves."
Although other tRNA halves have been described before -- specifically those that are produced during a cellular stress response -- this discovery represents a new and distinct species of tRNA halves that the authors coined SHOT-RNAs, for sex hormone dependent tRNA-derived RNAs.
Dr. Kirino and colleagues discovered these tRNA halves while looking at germline-specific small RNAs in the cells of a silkworm (Bombyx mori). In the cells, the researchers accidentally detected the tRNA halves whose expression was linked to cell proliferation. Since proliferation is a hallmark of cancer cells, the researchers analyzed the involvement of tRNA halves in tumorigenesis.
Using a new TaqMan PCR-based technique, the researchers screened a number of cancer cell lines from various tissues, and discovered that tRNA halves were specifically expressed in large quantities in sex hormone-dependent cancers, i.e., estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer that are driven by the hormones estrogen and testosterone. After confirming the dependency of the tRNA halves' expression on the hormones and their receptors, they coined the new tRNA halves, SHOT-RNAs.
SHOT-RNAs contain a terminal modification which prevents their detection by standard RNA-seq method. "The modification makes SHOT-RNAs invisible in RNA-seq data and this could be the reason why SHOT-RNAs had not been discovered in spite of their abundance and clear expression specificity in hormone-dependent cancers," says Dr. Kirino.
Dr. Kirino and colleagues created a novel method called cP-RNA-seq to comprehensively sequence SHOT-RNAs and found that only eight tRNA species produce SHOT-RNAs. They were also able to track the molecule's function in the cells, and tease apart the other cellular players it interacted with. They discovered, for example, that SHOT-RNAs are created by an enzyme called Angiogenin whose activity is promoted by sex hormone signaling pathways. They also showed that SHOT-RNAs are involved in spurring cell proliferation.
"The SHOT-RNAs are an exciting development in the tRNA field," said Isidore Rigoutsos, Ph.D., Director of the Computational Medicine Center at Thomas Jefferson University. "They are also another example of what appear to be regulators whose presence in a given tissue is modulated by a person's gender. Discovering such regulators is one of the major foci of the Computational Medicine Center."
In a final experiment, Dr. Kirino and colleagues also examined clinical samples from breast cancer patients and found elevated levels of SHOT-RNAs in patients with ER-positive luminal-type cancers, but not those that were negative for ER expression. The high expression specificity of SHOT-RNAs implies their potential use as a novel biomarker, and the next steps, says Dr. Kirino, are to explore relationships between SHOT-RNA expression and prognostic factors.
In spite of endocrine therapy to suppress hormone receptor activity or hormone exposure, many patients of hormone-dependent cancers encounter de novo or acquired resistance and require more aggressive treatments. Dr. Kirino says that "further studies to understand how SHOT-RNAs promote cell proliferation may lead to the use of SHOT-RNAs as potential target candidates for future therapeutic applications in breast and prostate cancers."
Read more:http://www.cusabio.com/catalog-15-1.html
2015年6月28日星期日
New antibody weapons against Marburg virus
A new study led by scientists at The Scripps Research Institute (TSRI)
identifies new immune molecules that protect against deadly Marburg virus, a
relative of Ebola virus. The research provides ingredients needed to develop
treatments for future Marburg outbreaks.
"These antibodies attack a new site on Marburg virus we had not seen before," said Erica Ollmann Saphire, senior author of the new study, professor at TSRI and director of the Viral Hemorrhagic Fever Immunotherapeutic Consortium.
The new antibodies that identify and neutralize Marburg virus -- which has a mortality rate of up to 90% -- were developed through an academic-industrial partnership including TSRI, Integrated Biotherapeutics, Mapp Biopharmaceutical and Emergent BioSolutions. Currently, there are no vaccines or treatments specifically for Marburg infections.
The findings were published online ahead of print June 26 in the journal PloS Pathogens.
New Tools to Fight Marburg Virus
The new study builds on previous work in Saphire's lab revealing a molecular structure that Marburg virus uses to attach to and enter host cells.
To defeat Marburg virus, scientists are looking for vulnerable sites on the virus's surface where an antibody can bind. Previous research, including trials with the experimental ZMappTM treatment, shows that mixtures or "cocktails" of antibodies can block Ebola virus from infecting new cells and alert the immune system to the presence of the infection. It's thought that a similar cocktail strategy could work against Marburg virus. Antibodies against one site on Marburg were revealed in a study by Vanderbilt University and TSRI in February 2015, but complementary antibodies needed against other sites remained to be discovered.
In the new study, TSRI researchers designed proteins which elicited new antibodies developed at Emergent BioSolutions. Other antibodies in the study were independently identified at Mapp Biopharmaceutical and Integrated Biotherapeutics, which collaborated with TSRI for molecular analysis.
Some of the new antibodies target a new site on Marburg virus not seen before -- a wing-like feature attached to the base of the virus. Antibodies against this newly discovered site protected 90 to 100% of infected animal models from lethal infection.
Ebola Virus Also Vulnerable
Some antibodies discovered in the new study are also able to cross-react with Ebola virus and its four relatives in the Ebolavirus genus.
"We expect both Marburg virus and Ebola virus to emerge again and to acquire new mutations," said TSRI Research Assistant Marnie Fusco, first author of the new study. "The cross-reactive antibodies could be used as diagnostics for newly emerging strains."
"The high cost of creating independent vaccines or treatments for each of the different viruses in this family necessitates intelligent design of immunogens (antibody-inducing molecules). The molecular images used to design the molecules and evaluate the antibodies point the way forward," added Jody Berry, the former Director of Pipeline Research of Emergent BioSolutions, who initiated the study with Saphire six years ago.
"Understanding where and how the antibodies interact with the virus tells us which regions can be targeted and helps us develop lead candidates for clinical development," said Cory Nykiforuk, current director of pipeline research of Emergent BioSolutions. "There are multiple filoviruses that threaten our communities, front line medical workers and defense personnel, and bringing new technologies to the forefront could potentially help meet future requirements."
Read more:http://www.cusabio.com/catalog-14-1.html
"These antibodies attack a new site on Marburg virus we had not seen before," said Erica Ollmann Saphire, senior author of the new study, professor at TSRI and director of the Viral Hemorrhagic Fever Immunotherapeutic Consortium.
The new antibodies that identify and neutralize Marburg virus -- which has a mortality rate of up to 90% -- were developed through an academic-industrial partnership including TSRI, Integrated Biotherapeutics, Mapp Biopharmaceutical and Emergent BioSolutions. Currently, there are no vaccines or treatments specifically for Marburg infections.
The findings were published online ahead of print June 26 in the journal PloS Pathogens.
New Tools to Fight Marburg Virus
The new study builds on previous work in Saphire's lab revealing a molecular structure that Marburg virus uses to attach to and enter host cells.
To defeat Marburg virus, scientists are looking for vulnerable sites on the virus's surface where an antibody can bind. Previous research, including trials with the experimental ZMappTM treatment, shows that mixtures or "cocktails" of antibodies can block Ebola virus from infecting new cells and alert the immune system to the presence of the infection. It's thought that a similar cocktail strategy could work against Marburg virus. Antibodies against one site on Marburg were revealed in a study by Vanderbilt University and TSRI in February 2015, but complementary antibodies needed against other sites remained to be discovered.
In the new study, TSRI researchers designed proteins which elicited new antibodies developed at Emergent BioSolutions. Other antibodies in the study were independently identified at Mapp Biopharmaceutical and Integrated Biotherapeutics, which collaborated with TSRI for molecular analysis.
Some of the new antibodies target a new site on Marburg virus not seen before -- a wing-like feature attached to the base of the virus. Antibodies against this newly discovered site protected 90 to 100% of infected animal models from lethal infection.
Ebola Virus Also Vulnerable
Some antibodies discovered in the new study are also able to cross-react with Ebola virus and its four relatives in the Ebolavirus genus.
"We expect both Marburg virus and Ebola virus to emerge again and to acquire new mutations," said TSRI Research Assistant Marnie Fusco, first author of the new study. "The cross-reactive antibodies could be used as diagnostics for newly emerging strains."
"The high cost of creating independent vaccines or treatments for each of the different viruses in this family necessitates intelligent design of immunogens (antibody-inducing molecules). The molecular images used to design the molecules and evaluate the antibodies point the way forward," added Jody Berry, the former Director of Pipeline Research of Emergent BioSolutions, who initiated the study with Saphire six years ago.
"Understanding where and how the antibodies interact with the virus tells us which regions can be targeted and helps us develop lead candidates for clinical development," said Cory Nykiforuk, current director of pipeline research of Emergent BioSolutions. "There are multiple filoviruses that threaten our communities, front line medical workers and defense personnel, and bringing new technologies to the forefront could potentially help meet future requirements."
Read more:http://www.cusabio.com/catalog-14-1.html
2015年6月25日星期四
Researchers develop innovative gene transfer-based treatment approach
University of North Carolina (UNC) School of Medicine researchers have developed an innovative, experimental gene transfer-based treatment for children with giant axonal neuropathy (GAN).
Researchers led by Steven J. Gray, PhD, assistant professor in the Department of Ophthalmology and a researcher in UNC's Gene Therapy Center and Carolina Institute for Developmental Disabilities, developed the experimental treatment in studies conducted at UNC. Gray's work in this area was funded almost entirely by Hannah's Hope Fund, a charity founded by the parents of Hannah Sames, an 11-year-old girl with giant axonal neuropathy (GAN), to support the development of a treatment and cure. This extremely rare genetic disorder causes children to gradually lose the ability to balance themselves, move their muscles and to feel certain sensations. Most children born with GAN do not survive beyond their early 20s because of progressive impairment of their ability to breath.
The treatment approach developed at UNC uses a genetically modified virus called AAV to deliver a missing gene, the gigaxonin gene (scAAV9/JeT-GAN), into the cerebrospinal fluid of children with GAN. The therapeutic viral vector to be used in each of these injections is prepared at the UNC Vector Core Human Applications Laboratory.
A clinical trial of this approach is now underway at the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) in Bethesda, Maryland. The first patient was enrolled in May. This is the first gene delivery approach directly into the spinal fluid in order to treat an inherited neurological disorder, and is expected to pave the way to developing treatments for many other related diseases.
Gray chose to focus his career on this rare genetic condition after meeting Hannah, who is the same age as his own daughter, Aubrey.
"This has been a coordinated and committed effort between Hannah's Hope and UNC to drive a treatment forward for GAN. Hannah's Hope is a truly amazing community that provides a constant source of inspiration. Our goal has always been to bring hope to the families affected by this devastating disease, and we are proud to be taking the first step to making a GAN treatment a reality," said Dr. Gray. "We are greatly appreciative of NIH/NINDS for partnering with us on this life-saving mission. This trial is the first in history to deliver gene therapy through the spinal fluid to test the potential to achieve broad treatment of the spinal cord and brain (central nervous system or CNS). It is a momentous step forward, and we're already seeing clear application of this approach to treat other diseases studied in my lab."
Gray serves as an associate investigator on the trial as does R. Jude Samulski, PhD, director of the UNC Gene Therapy Center.
"After 30 years of focusing on optimizing successful gene delivery, it is very rewarding to finally see these approaches being tested for some of the unmet clinical needs caused by these terminal genetic disorders," Samulski said. "This specific study represents a culmination of years of basic research from the UNC Gene Therapy Center and that primarily of Steve Gray's team coupled with clinical expertise at the NIH. More importantly, this journey for me has personally been a truly rewarding one that started seven years ago with a parent knocking on the office door asking if we could 'help save her child', to last week's gene therapy administration; a remarkable and humbling journey that I'm privileged to be a part of."
Carsten Bönnemann, MD, who is leading the trial at NIH said, "This first intrathecal (into the spinal fluid) delivery of a viral gene therapy vector in a human patient is a fundamental step towards developing a causal treatment for giant axonal neuropathy (GAN), a devastating progressive neurogenetic disorder of childhood. At the same time it is also paving the way for similar gene transfer based treatments for many other neurological disorders in which nerve cells of the spinal cord and brain need to be targeted, including spinal muscular atrophy. Bringing such path-breaking treatments to children affected by neurogenetic disorders is really the core mission of our team here at the NINDS so we are very excited to be helping to move this approach to a clinical trial. That this first step is now being taken is testament to Hannah's Hope Fund and Dr. Steve Gray's tenacity and enormous commitment, but also to the courage of our first young patient who volunteered to receive this treatment, and others who will follow."
The Phase I clinical trial, which officially started in January, seeks to enroll a total of up to 20 patients with GAN who are ages five and older. Each of the children and their families will be required to live within 100 miles of the NIH for two months after receiving the gene transfer treatment, which will be given by a single injection by spinal tap into their cerebrospinal fluid, which flows around the brain and spinal cord.
Read more:http://www.cusabio.com/
Researchers led by Steven J. Gray, PhD, assistant professor in the Department of Ophthalmology and a researcher in UNC's Gene Therapy Center and Carolina Institute for Developmental Disabilities, developed the experimental treatment in studies conducted at UNC. Gray's work in this area was funded almost entirely by Hannah's Hope Fund, a charity founded by the parents of Hannah Sames, an 11-year-old girl with giant axonal neuropathy (GAN), to support the development of a treatment and cure. This extremely rare genetic disorder causes children to gradually lose the ability to balance themselves, move their muscles and to feel certain sensations. Most children born with GAN do not survive beyond their early 20s because of progressive impairment of their ability to breath.
The treatment approach developed at UNC uses a genetically modified virus called AAV to deliver a missing gene, the gigaxonin gene (scAAV9/JeT-GAN), into the cerebrospinal fluid of children with GAN. The therapeutic viral vector to be used in each of these injections is prepared at the UNC Vector Core Human Applications Laboratory.
A clinical trial of this approach is now underway at the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) in Bethesda, Maryland. The first patient was enrolled in May. This is the first gene delivery approach directly into the spinal fluid in order to treat an inherited neurological disorder, and is expected to pave the way to developing treatments for many other related diseases.
Gray chose to focus his career on this rare genetic condition after meeting Hannah, who is the same age as his own daughter, Aubrey.
"This has been a coordinated and committed effort between Hannah's Hope and UNC to drive a treatment forward for GAN. Hannah's Hope is a truly amazing community that provides a constant source of inspiration. Our goal has always been to bring hope to the families affected by this devastating disease, and we are proud to be taking the first step to making a GAN treatment a reality," said Dr. Gray. "We are greatly appreciative of NIH/NINDS for partnering with us on this life-saving mission. This trial is the first in history to deliver gene therapy through the spinal fluid to test the potential to achieve broad treatment of the spinal cord and brain (central nervous system or CNS). It is a momentous step forward, and we're already seeing clear application of this approach to treat other diseases studied in my lab."
Gray serves as an associate investigator on the trial as does R. Jude Samulski, PhD, director of the UNC Gene Therapy Center.
"After 30 years of focusing on optimizing successful gene delivery, it is very rewarding to finally see these approaches being tested for some of the unmet clinical needs caused by these terminal genetic disorders," Samulski said. "This specific study represents a culmination of years of basic research from the UNC Gene Therapy Center and that primarily of Steve Gray's team coupled with clinical expertise at the NIH. More importantly, this journey for me has personally been a truly rewarding one that started seven years ago with a parent knocking on the office door asking if we could 'help save her child', to last week's gene therapy administration; a remarkable and humbling journey that I'm privileged to be a part of."
Carsten Bönnemann, MD, who is leading the trial at NIH said, "This first intrathecal (into the spinal fluid) delivery of a viral gene therapy vector in a human patient is a fundamental step towards developing a causal treatment for giant axonal neuropathy (GAN), a devastating progressive neurogenetic disorder of childhood. At the same time it is also paving the way for similar gene transfer based treatments for many other neurological disorders in which nerve cells of the spinal cord and brain need to be targeted, including spinal muscular atrophy. Bringing such path-breaking treatments to children affected by neurogenetic disorders is really the core mission of our team here at the NINDS so we are very excited to be helping to move this approach to a clinical trial. That this first step is now being taken is testament to Hannah's Hope Fund and Dr. Steve Gray's tenacity and enormous commitment, but also to the courage of our first young patient who volunteered to receive this treatment, and others who will follow."
The Phase I clinical trial, which officially started in January, seeks to enroll a total of up to 20 patients with GAN who are ages five and older. Each of the children and their families will be required to live within 100 miles of the NIH for two months after receiving the gene transfer treatment, which will be given by a single injection by spinal tap into their cerebrospinal fluid, which flows around the brain and spinal cord.
Read more:http://www.cusabio.com/
2015年6月24日星期三
DNA shed from head and neck tumors detected in blood, saliva
On the hunt for better cancer screening tests, Johns Hopkins scientists led
a proof of principle study that successfully identified tumor DNA shed into the
blood and saliva of 93 patients with head and neck cancer. A report on the
findings is published in the June 24 issue of Science Translational
Medicine.
"We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers," says Nishant Agrawal, M.D., associate professor of otolaryngology -- head and neck surgery -- and of oncology at the Johns Hopkins University School of Medicine. "In our study, testing saliva seemed to be the best way to detect cancers in the oral cavity, and blood tests appeared to find more cancers in the larynx, hypopharynx and oropharynx. However, combining blood and saliva tests may offer the best chance of finding cancer in any of those regions."
Agrawal explains that inborn genetic predispositions for most head and neck cancers are rare, but other mutations that don't generally occur in normal cells have long been considered good targets for screening tests.
In the case of head and neck cancers associated with HPV -- tumors on the rise among Americans -- Agrawal and his colleagues searched patients' blood and saliva samples for certain tumor-promoting, HPV-related DNA. For non-HPV-related cancers, which account for the worldwide majority of head and neck tumors, they looked for mutations in cancer-related genes that included TP53, PIK3CA, CDKN2A, FBXW7, HRAS and NRAS.
The major risk factors for head and neck cancers are alcohol, tobacco -- including chewing tobacco -- and HPV infection.
For the study, 93 patients with newly diagnosed and recurrent head and neck cancer gave saliva samples, and 47 of them also donated blood samples before their treatment at The Johns Hopkins Hospital and MD Anderson Cancer Center in Texas. The scientists detected tumor DNA in the saliva of 71 of the 93 patients (76 percent) and in the blood of 41 of the 47 (87 percent). In the 47 who gave blood and saliva samples, scientists were able to detect tumor DNA in at least one of the body fluids in 45 of them (96 percent).
When the scientists analyzed how well their tumor DNA tests found cancers in certain regions of the head and neck, they found that saliva tests fared better than blood tests for oral cavity cancers. All 46 oral cavity cancers were correctly identified through saliva tests, compared with 16 of 34 oropharynx cancers (47 percent), seven of 10 larynx cancers (70 percent) and two of three hypopharynx cancers (67 percent).
The oral cavity refers to areas within the mouth, including the lips, front of the tongue, cheeks and gums. The oropharynx and hypopharynx are located in the back of the throat. The larynx, also in the throat, is typically known as the voice box.
"One reason that saliva tests may not have been as effective for cancer sites in the back of the throat is because we didn't ask patients to gargle; we only asked them to rinse their mouths to provide the samples," says Agrawal, a member of Johns Hopkins' Kimmel Cancer Center and Ludwig Center.
Blood tests correctly identified tumor DNA more often in 20 of 22 oropharynx cancers (91 percent), six of seven larynx cancers (86 percent) and all three hypopharynx cancers. Taken together, blood and saliva tests correctly identified all oral cavity, larynx and hypopharynx cancers and 20 of 22 oropharynx cancers (91 percent).
Agrawal says the sensitivity of the tests overall depended on the cancer site, stage and HPV status, ranging between 86 to 100 percent. He also reports that saliva tests performed better for early-stage cancers, finding all 20 cancers, compared with blood tests that correctly identified seven of 10. He and his team found the opposite was true for late-stage cancers: Blood tests found more late-stage cancers (34 of 37), compared with saliva tests (51 of 73). Blood tests also correctly identified HPV-related tumors, occurring in 30 of the 93 patients, more often than saliva tests, probably because HPV-related tumors tend to occur in the back of the throat, which may not have been reached with the saliva rinse.
"Our ultimate goal is to develop better screening tests to find head and neck cancers among the general population and improve how we monitor patients with cancer for recurrence of their disease," says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins Kimmel Cancer Center, co-director of the Ludwig Center at Johns Hopkins and a co-author of the study.
The scientists caution that further study of their tumor DNA detection method in larger groups of patients and healthy people is needed before clinical effectiveness can be determined, and that refinements also may be needed in methods of collecting saliva and the range of cancer-specific genes in the gene test panel.
In addition, Agrawal says: "We don't yet have definitive data on false positive rates, and won't until there are more studies of the tests in healthy people." However, he notes, the formulas used to analyze their blood and saliva tests are designed to weed out questionable results.
False results in gene tests arise when DNA are copied many times, sequenced and analyzed. The scientists used a method they developed and tested previously in cervical fluid to find ovarian and cervical cancers. Specifically, they attach a kind of genetic bar code -- a random set of 14 DNA base pairs -- to trace each copied DNA fragment to its original one. DNA copies lacking the bar code are suspected to be an artifact of the process, and any mutation found in it is disregarded.
Agrawal says that tests like the one his team used, if used commercially, likely would cost several hundred dollars, and "our long-term goal is to create a test that costs less than $50 so it can be administered by physicians or dentists."
To screen for head and neck cancers, which occur in more than 50,000 people in the U.S. each year, doctors conduct physical examinations. Biopsies are taken of suspicious-looking lesions, but "this method is not ideal, as evidenced by the fact that most head and neck cancers are rarely found at very early stages, when they are most curable," says Agrawal.
Read more:http://www.cusabio.com/catalog-15-1.html
"We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers," says Nishant Agrawal, M.D., associate professor of otolaryngology -- head and neck surgery -- and of oncology at the Johns Hopkins University School of Medicine. "In our study, testing saliva seemed to be the best way to detect cancers in the oral cavity, and blood tests appeared to find more cancers in the larynx, hypopharynx and oropharynx. However, combining blood and saliva tests may offer the best chance of finding cancer in any of those regions."
Agrawal explains that inborn genetic predispositions for most head and neck cancers are rare, but other mutations that don't generally occur in normal cells have long been considered good targets for screening tests.
In the case of head and neck cancers associated with HPV -- tumors on the rise among Americans -- Agrawal and his colleagues searched patients' blood and saliva samples for certain tumor-promoting, HPV-related DNA. For non-HPV-related cancers, which account for the worldwide majority of head and neck tumors, they looked for mutations in cancer-related genes that included TP53, PIK3CA, CDKN2A, FBXW7, HRAS and NRAS.
The major risk factors for head and neck cancers are alcohol, tobacco -- including chewing tobacco -- and HPV infection.
For the study, 93 patients with newly diagnosed and recurrent head and neck cancer gave saliva samples, and 47 of them also donated blood samples before their treatment at The Johns Hopkins Hospital and MD Anderson Cancer Center in Texas. The scientists detected tumor DNA in the saliva of 71 of the 93 patients (76 percent) and in the blood of 41 of the 47 (87 percent). In the 47 who gave blood and saliva samples, scientists were able to detect tumor DNA in at least one of the body fluids in 45 of them (96 percent).
When the scientists analyzed how well their tumor DNA tests found cancers in certain regions of the head and neck, they found that saliva tests fared better than blood tests for oral cavity cancers. All 46 oral cavity cancers were correctly identified through saliva tests, compared with 16 of 34 oropharynx cancers (47 percent), seven of 10 larynx cancers (70 percent) and two of three hypopharynx cancers (67 percent).
The oral cavity refers to areas within the mouth, including the lips, front of the tongue, cheeks and gums. The oropharynx and hypopharynx are located in the back of the throat. The larynx, also in the throat, is typically known as the voice box.
"One reason that saliva tests may not have been as effective for cancer sites in the back of the throat is because we didn't ask patients to gargle; we only asked them to rinse their mouths to provide the samples," says Agrawal, a member of Johns Hopkins' Kimmel Cancer Center and Ludwig Center.
Blood tests correctly identified tumor DNA more often in 20 of 22 oropharynx cancers (91 percent), six of seven larynx cancers (86 percent) and all three hypopharynx cancers. Taken together, blood and saliva tests correctly identified all oral cavity, larynx and hypopharynx cancers and 20 of 22 oropharynx cancers (91 percent).
Agrawal says the sensitivity of the tests overall depended on the cancer site, stage and HPV status, ranging between 86 to 100 percent. He also reports that saliva tests performed better for early-stage cancers, finding all 20 cancers, compared with blood tests that correctly identified seven of 10. He and his team found the opposite was true for late-stage cancers: Blood tests found more late-stage cancers (34 of 37), compared with saliva tests (51 of 73). Blood tests also correctly identified HPV-related tumors, occurring in 30 of the 93 patients, more often than saliva tests, probably because HPV-related tumors tend to occur in the back of the throat, which may not have been reached with the saliva rinse.
"Our ultimate goal is to develop better screening tests to find head and neck cancers among the general population and improve how we monitor patients with cancer for recurrence of their disease," says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins Kimmel Cancer Center, co-director of the Ludwig Center at Johns Hopkins and a co-author of the study.
The scientists caution that further study of their tumor DNA detection method in larger groups of patients and healthy people is needed before clinical effectiveness can be determined, and that refinements also may be needed in methods of collecting saliva and the range of cancer-specific genes in the gene test panel.
In addition, Agrawal says: "We don't yet have definitive data on false positive rates, and won't until there are more studies of the tests in healthy people." However, he notes, the formulas used to analyze their blood and saliva tests are designed to weed out questionable results.
False results in gene tests arise when DNA are copied many times, sequenced and analyzed. The scientists used a method they developed and tested previously in cervical fluid to find ovarian and cervical cancers. Specifically, they attach a kind of genetic bar code -- a random set of 14 DNA base pairs -- to trace each copied DNA fragment to its original one. DNA copies lacking the bar code are suspected to be an artifact of the process, and any mutation found in it is disregarded.
Agrawal says that tests like the one his team used, if used commercially, likely would cost several hundred dollars, and "our long-term goal is to create a test that costs less than $50 so it can be administered by physicians or dentists."
To screen for head and neck cancers, which occur in more than 50,000 people in the U.S. each year, doctors conduct physical examinations. Biopsies are taken of suspicious-looking lesions, but "this method is not ideal, as evidenced by the fact that most head and neck cancers are rarely found at very early stages, when they are most curable," says Agrawal.
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2015年6月23日星期二
Study identifies multiple genetic changes linked to increased pancreatic cancer risk
In a genome-wide association study believed to be the largest of its kind,
Johns Hopkins researchers have uncovered four regions in the human genome where
changes may increase the risk of pancreatic cancer.
The researchers say newly identified genetic variants are located at several positions on human chromosomes, including position 17q25.1, which may increase cancer risk by 38 percent for each copy that is present in the genome; position 7p13, which may increase the risk by 12 percent; and position 3q29, which may increase the risk by 16 percent. Position 2p13.3, another genetic region pinpointed in the study, was previously linked with pancreatic cancer risk in a study of Han Chinese people, and the current study provides more definitive evidence of different genetic changes in that region believed to increase pancreatic cancer risk by 14 percent.
"These variants are common in the population, and most individuals who have these variants will never develop pancreatic cancer in their lifetime," cautions Alison Klein, Ph.D., associate professor of oncology at the Johns Hopkins University School of Medicine. "However, identifying and understanding these changes can lead to a better understanding of why some people develop pancreatic cancer. If we combine this information with data on other pancreatic cancer risk factors, we may be able to identify and one day screen high-risk groups."
Further studies of the function of these genetic regions are already underway, Klein says, but several appear related to DNA repair, cell growth and tumor suppression.
Results of the genomic analysis, published online June 22 in Nature Genetics by Klein and her colleagues, included genetic information from 9,925 patients with pancreatic cancer and 11,569 healthy individuals. Some of the samples were newly genotyped, and others were analyzed in a so-called meta-analysis of already published data. The newly-genotyped blood samples were obtained from eight medical centers in North America, central Europe and Australia, and took four years to collect and analyze.
Klein, a member of the Johns Hopkins Kimmel Cancer Center and Sol Goldman Pancreatic Cancer Research Center, says the study also confirms the connection between pancreatic cancer risk and several genetic variants linked to other cancers. For instance, the scientists noted a connection between pancreatic cancer risk and variation in the TP63 gene, and other studies have suggested the TP63 variations also are related to lung and bladder cancers, among others.
"We knew there were more genetic variants to be found, and the large number of pancreatic cancers in the current analysis gave our study more power to find more novel genes," she says.
Pancreatic cancer is the fourth leading cause of cancer death in the United States, but it is not as commonly diagnosed as other cancers, such as breast or colorectal cancers. Patients with pancreatic cancer are also often diagnosed at late stages of the disease, making it tougher to identify genetic risk factors, says Klein.
Klein noted that for some of the new and previously reported variants identified by comparing the genomes of patients with pancreatic cancer and healthy people, scientists cannot say how or why they have an impact on pancreatic cancer. "Sometimes the variation doesn't have an effect on the gene it's in or near, but it could have a more distant target. We need further studies to learn how the increased risk arises."
Because smoking is a well-established risk factor for many cancers, the researchers also re-examined the changes in nine of the new and previously discovered genetic regions in smokers and nonsmokers. They found no evidence that smoking impacted the link between those particular variants and pancreatic cancer risk. She emphasized that this does not mean there is no increased risk among smokers, but that these changes are equally important in both smokers and non-smokers.
Klein and colleagues hope to increase the number of pancreatic cancer cases in future genome-wide association studies and include patients from other geographic regions, such as Asia. "While this study increases our understanding of the genetic basis of pancreatic cancer, we do know from our analysis that there are lots of other variants we need to find to fully understand it," says Klein.
The ultimate goal of these genetic studies, says Klein, is to pinpoint the causes of pancreatic cancer, helping scientists develop better treatment and early detection screening for the disease, which has only a 5 to 7 percent survival rate five years after diagnosis. Currently, these new variants are not included in any genetic screening of healthy individuals, but the aim, Klein says, is to identify high-risk populations.
"If we can identify high-risk populations, we can eventually get to the point where we can detect pancreatic cancer early, when the disease is most treatable, and save lives," Klein notes.
Read more:http://www.cusabio.com/catalog-15-1.html
The researchers say newly identified genetic variants are located at several positions on human chromosomes, including position 17q25.1, which may increase cancer risk by 38 percent for each copy that is present in the genome; position 7p13, which may increase the risk by 12 percent; and position 3q29, which may increase the risk by 16 percent. Position 2p13.3, another genetic region pinpointed in the study, was previously linked with pancreatic cancer risk in a study of Han Chinese people, and the current study provides more definitive evidence of different genetic changes in that region believed to increase pancreatic cancer risk by 14 percent.
"These variants are common in the population, and most individuals who have these variants will never develop pancreatic cancer in their lifetime," cautions Alison Klein, Ph.D., associate professor of oncology at the Johns Hopkins University School of Medicine. "However, identifying and understanding these changes can lead to a better understanding of why some people develop pancreatic cancer. If we combine this information with data on other pancreatic cancer risk factors, we may be able to identify and one day screen high-risk groups."
Further studies of the function of these genetic regions are already underway, Klein says, but several appear related to DNA repair, cell growth and tumor suppression.
Results of the genomic analysis, published online June 22 in Nature Genetics by Klein and her colleagues, included genetic information from 9,925 patients with pancreatic cancer and 11,569 healthy individuals. Some of the samples were newly genotyped, and others were analyzed in a so-called meta-analysis of already published data. The newly-genotyped blood samples were obtained from eight medical centers in North America, central Europe and Australia, and took four years to collect and analyze.
Klein, a member of the Johns Hopkins Kimmel Cancer Center and Sol Goldman Pancreatic Cancer Research Center, says the study also confirms the connection between pancreatic cancer risk and several genetic variants linked to other cancers. For instance, the scientists noted a connection between pancreatic cancer risk and variation in the TP63 gene, and other studies have suggested the TP63 variations also are related to lung and bladder cancers, among others.
"We knew there were more genetic variants to be found, and the large number of pancreatic cancers in the current analysis gave our study more power to find more novel genes," she says.
Pancreatic cancer is the fourth leading cause of cancer death in the United States, but it is not as commonly diagnosed as other cancers, such as breast or colorectal cancers. Patients with pancreatic cancer are also often diagnosed at late stages of the disease, making it tougher to identify genetic risk factors, says Klein.
Klein noted that for some of the new and previously reported variants identified by comparing the genomes of patients with pancreatic cancer and healthy people, scientists cannot say how or why they have an impact on pancreatic cancer. "Sometimes the variation doesn't have an effect on the gene it's in or near, but it could have a more distant target. We need further studies to learn how the increased risk arises."
Because smoking is a well-established risk factor for many cancers, the researchers also re-examined the changes in nine of the new and previously discovered genetic regions in smokers and nonsmokers. They found no evidence that smoking impacted the link between those particular variants and pancreatic cancer risk. She emphasized that this does not mean there is no increased risk among smokers, but that these changes are equally important in both smokers and non-smokers.
Klein and colleagues hope to increase the number of pancreatic cancer cases in future genome-wide association studies and include patients from other geographic regions, such as Asia. "While this study increases our understanding of the genetic basis of pancreatic cancer, we do know from our analysis that there are lots of other variants we need to find to fully understand it," says Klein.
The ultimate goal of these genetic studies, says Klein, is to pinpoint the causes of pancreatic cancer, helping scientists develop better treatment and early detection screening for the disease, which has only a 5 to 7 percent survival rate five years after diagnosis. Currently, these new variants are not included in any genetic screening of healthy individuals, but the aim, Klein says, is to identify high-risk populations.
"If we can identify high-risk populations, we can eventually get to the point where we can detect pancreatic cancer early, when the disease is most treatable, and save lives," Klein notes.
Read more:http://www.cusabio.com/catalog-15-1.html
2015年6月22日星期一
Research team evolves CRISPR-Cas9 nucleases with novel properties
A team of Massachusetts General Hospital (MGH) researchers has found a way
to expand the use and precision of the powerful gene-editing tools called
CRISPR-Cas9 RNA-guided nucleases. In their report receiving advance online
release in Nature, the investigators describe evolved versions of the
DNA-cutting Cas9 enzyme that are able to recognize a different range of nucleic
acid sequences than is possible with the naturally occurring form of Cas9 that
has been used to date.
"In our paper we show that sites in human and zebrafish genes that could not previously be modified by wild-type Cas9 can now be targeted with the new variants we have engineered," says Benjamin Kleinstiver, PhD, a research fellow in the MGH Molecular Pathology Unit and lead author of the Naturepaper. "This will allow researchers to target an expanded range of sites in a variety of genomes, which will be useful for applications requiring highly precise targeting of DNA sequences."
CRISPR-Cas9 nucleases consist of the Cas9 bacterial enzyme and a short, 20-nucleotide RNA molecule that matches the target DNA sequence. In addition to the RNA/DNA match, the Cas9 enzyme needs to recognize a specific nucleotide sequence called a protospacer adjacent motif (PAM) adjacent to the target DNA. The most commonly used form of Cas9, derived from the bacteria Streptococcus pyogenes and known as SpCas9, recognizes PAM sequences in which any nucleotide is followed by two guanine DNA bases. This limits the DNA sequences that can be targeted using SpCas9 only to those that include two sequential guanines.
To get around this limitation the MGH team set up an engineering system that allowed them to rapidly evolve the ability of SpCas9 to recognize different PAM sequences. From a collection of randomly mutated SpCas9 variants, they identified combinations of mutations that enabled SpCas9 to recognize new PAM sequences. These evolved variants essentially double the range of sites that can now be targeted for gene editing using SpCas9. Fortuitously, they also identified an SpCas9 variant that was less likely to induce the off-target gene mutations sometimes produced by CRISPR-Cas9 nucleases, a problem originally described in a 2013 study led by J. Keith Joung, MD, PhD, associate chief of Research in the MGH Department of Pathology and senior author of the current study. "This additional evolved variant with increased specificity should be immediately useful to all researchers who currently use wild-type SpCas9 and should reduce the frequencies of unwanted off-target mutations," Joung says.
"Perhaps more importantly," he adds, "our findings provide the first demonstration that the activities of SpCas9 can be altered by directed protein evolution. In fact, we show in our paper that the forms of Cas9 found in two other bacteria - Staphylococcus aureus and Streptococcus thermophilus - can also function in our bacterial evolution system, suggesting that we should be able to modify their functions as well. This work just scratches the surface of the range of PAMs that can be targeted by Cas9, and we believe that other useful properties of the enzyme may be modified by a similar approach, allowing potential customization of many important features." Joung is a professor of Pathology at Harvard Medical School.
Read more:http://about.cusabio.com/m-188.html
"In our paper we show that sites in human and zebrafish genes that could not previously be modified by wild-type Cas9 can now be targeted with the new variants we have engineered," says Benjamin Kleinstiver, PhD, a research fellow in the MGH Molecular Pathology Unit and lead author of the Naturepaper. "This will allow researchers to target an expanded range of sites in a variety of genomes, which will be useful for applications requiring highly precise targeting of DNA sequences."
CRISPR-Cas9 nucleases consist of the Cas9 bacterial enzyme and a short, 20-nucleotide RNA molecule that matches the target DNA sequence. In addition to the RNA/DNA match, the Cas9 enzyme needs to recognize a specific nucleotide sequence called a protospacer adjacent motif (PAM) adjacent to the target DNA. The most commonly used form of Cas9, derived from the bacteria Streptococcus pyogenes and known as SpCas9, recognizes PAM sequences in which any nucleotide is followed by two guanine DNA bases. This limits the DNA sequences that can be targeted using SpCas9 only to those that include two sequential guanines.
To get around this limitation the MGH team set up an engineering system that allowed them to rapidly evolve the ability of SpCas9 to recognize different PAM sequences. From a collection of randomly mutated SpCas9 variants, they identified combinations of mutations that enabled SpCas9 to recognize new PAM sequences. These evolved variants essentially double the range of sites that can now be targeted for gene editing using SpCas9. Fortuitously, they also identified an SpCas9 variant that was less likely to induce the off-target gene mutations sometimes produced by CRISPR-Cas9 nucleases, a problem originally described in a 2013 study led by J. Keith Joung, MD, PhD, associate chief of Research in the MGH Department of Pathology and senior author of the current study. "This additional evolved variant with increased specificity should be immediately useful to all researchers who currently use wild-type SpCas9 and should reduce the frequencies of unwanted off-target mutations," Joung says.
"Perhaps more importantly," he adds, "our findings provide the first demonstration that the activities of SpCas9 can be altered by directed protein evolution. In fact, we show in our paper that the forms of Cas9 found in two other bacteria - Staphylococcus aureus and Streptococcus thermophilus - can also function in our bacterial evolution system, suggesting that we should be able to modify their functions as well. This work just scratches the surface of the range of PAMs that can be targeted by Cas9, and we believe that other useful properties of the enzyme may be modified by a similar approach, allowing potential customization of many important features." Joung is a professor of Pathology at Harvard Medical School.
Read more:http://about.cusabio.com/m-188.html
2015年6月18日星期四
Scientists shows AIDS vaccine candidate successfully 'primes' immune system
New research led by scientists at The Scripps Research Institute (TSRI),
International AIDS Vaccine Initiative (IAVI) and The Rockefeller University
shows in mice that an experimental vaccine candidate designed at TSRI can
stimulate the immune system activity necessary to stop HIV infection. The
findings could provide key information for the development of an effective AIDS
vaccine.
The research, published June 18, 2015 in concurrent studies in the journalsCell and Science, represents a leap forward in the effort to develop avaccine against HIV, which has so far struggled to elicit antibodies (immune system molecules) that can effectively fight off different strains of the virus.
"The results are pretty spectacular," said Dennis Burton, chair of the TSRI Department of Immunology and Microbial Science and scientific director of two centers at TSRI, the IAVI Neutralizing Antibody Consortium (NAC) and the National Institutes of Health (NIH) Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID).
The Science study was co-led by Burton, TSRI Professor and IAVI NAC Associate Director of Vaccine Design William Schief, and TSRI Professor David Nemazee. The Cell study was co-led by Schief and Michel Nussenzweig, who is Zanvil A. Cohn and Ralph M. Steinman Professor at The Rockefeller University and a Howard Hughes Medical Institute (HHMI) investigator.
A Huge Challenge
The researchers' long-term goal is to design a vaccine that prompts the body to produce antibodies that bind to HIV and prevent infection.
While many vaccines for other diseases use a dead or inactive version of the disease-causing microbe itself to trigger antibody production, immunizations with "native" HIV proteins are ineffective in triggering an effective immune response, due to HIV's ability to evade detection from the immune system and mutate rapidly into new strains.
This challenge has led many researchers to believe that a successful AIDS vaccine will need to consist of a series of related, but slightly different proteins (immunogens) to train the body to produce broadly neutralizing antibodies against HIV—a twist on the traditional "booster" shot, where a person is exposed to the same immunogen multiple times.
In the new studies, the scientists tested one of these potential proteins, an immunogen called eOD-GT8 60mer, a protein nanoparticle designed to bind and activate B cells needed to fight HIV. The eOD-GT8 60mer was developed in the Schief lab and tested in mouse models engineered by the Nemazee lab to produce antibodies that resemble human antibodies.
Using a technique called B cell sorting, the researchers showed that immunization with eOD-GT8 60mer produced antibody "precursors"—with some of the traits necessary to recognize and block HIV infection. This suggested that eOD-GT8 60mer could be a good candidate to serve as the first in a series of immunizations against HIV.
"The vaccine appears to work well in our mouse model to 'prime' the antibody response," added Nemazee.
In the Cell paper, researchers used the same eOD-GT8 60mer immunogen but used a slightly different mouse model. "The immunogen again launched the immune system in the right direction," said Schief.
A concurrent study also in Science (led by Professor John Moore of Weill Cornell Medical College and including contributions from Schief, Burton, TSRI Associate Professor Andrew Ward, Ian Wilson, who is Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI, and other researchers) showed engineered immunogens also triggered immune responses in rabbit models and non-human primate models.
Next Steps
With eOD-GT8 60mer in the running as a potential contributor to an HIV vaccine, the researchers are now investigating other immunogens that could work in conjunction with it.
Schief said the Nemazee lab's mouse models will be crucial resources for testing other engineered immunogens. He emphasized the importance of bringing different disciplines together to engineer mouse models, design antibodies and analyze results. "This was a beautiful collaboration of three labs at TSRI," said Schief.
Read more:http://about.cusabio.com/m-219.html
The research, published June 18, 2015 in concurrent studies in the journalsCell and Science, represents a leap forward in the effort to develop avaccine against HIV, which has so far struggled to elicit antibodies (immune system molecules) that can effectively fight off different strains of the virus.
"The results are pretty spectacular," said Dennis Burton, chair of the TSRI Department of Immunology and Microbial Science and scientific director of two centers at TSRI, the IAVI Neutralizing Antibody Consortium (NAC) and the National Institutes of Health (NIH) Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID).
The Science study was co-led by Burton, TSRI Professor and IAVI NAC Associate Director of Vaccine Design William Schief, and TSRI Professor David Nemazee. The Cell study was co-led by Schief and Michel Nussenzweig, who is Zanvil A. Cohn and Ralph M. Steinman Professor at The Rockefeller University and a Howard Hughes Medical Institute (HHMI) investigator.
A Huge Challenge
The researchers' long-term goal is to design a vaccine that prompts the body to produce antibodies that bind to HIV and prevent infection.
While many vaccines for other diseases use a dead or inactive version of the disease-causing microbe itself to trigger antibody production, immunizations with "native" HIV proteins are ineffective in triggering an effective immune response, due to HIV's ability to evade detection from the immune system and mutate rapidly into new strains.
This challenge has led many researchers to believe that a successful AIDS vaccine will need to consist of a series of related, but slightly different proteins (immunogens) to train the body to produce broadly neutralizing antibodies against HIV—a twist on the traditional "booster" shot, where a person is exposed to the same immunogen multiple times.
In the new studies, the scientists tested one of these potential proteins, an immunogen called eOD-GT8 60mer, a protein nanoparticle designed to bind and activate B cells needed to fight HIV. The eOD-GT8 60mer was developed in the Schief lab and tested in mouse models engineered by the Nemazee lab to produce antibodies that resemble human antibodies.
Using a technique called B cell sorting, the researchers showed that immunization with eOD-GT8 60mer produced antibody "precursors"—with some of the traits necessary to recognize and block HIV infection. This suggested that eOD-GT8 60mer could be a good candidate to serve as the first in a series of immunizations against HIV.
"The vaccine appears to work well in our mouse model to 'prime' the antibody response," added Nemazee.
In the Cell paper, researchers used the same eOD-GT8 60mer immunogen but used a slightly different mouse model. "The immunogen again launched the immune system in the right direction," said Schief.
A concurrent study also in Science (led by Professor John Moore of Weill Cornell Medical College and including contributions from Schief, Burton, TSRI Associate Professor Andrew Ward, Ian Wilson, who is Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI, and other researchers) showed engineered immunogens also triggered immune responses in rabbit models and non-human primate models.
Next Steps
With eOD-GT8 60mer in the running as a potential contributor to an HIV vaccine, the researchers are now investigating other immunogens that could work in conjunction with it.
Schief said the Nemazee lab's mouse models will be crucial resources for testing other engineered immunogens. He emphasized the importance of bringing different disciplines together to engineer mouse models, design antibodies and analyze results. "This was a beautiful collaboration of three labs at TSRI," said Schief.
Read more:http://about.cusabio.com/m-219.html
2015年6月17日星期三
Blood protein may indicate risk of Alzheimer's disease
Scientists at King's College London have identified a single blood protein
that may indicate the development of Mild Cognitive Impairment (MCI) years
before symptoms appear, a disorder that has been associated with an increased
risk of Alzheimer's disease or other dementias.
The new research, published today in Translational Psychiatry, used data from over 100 sets of identical twins from TwinsUK, the biggest adult twin cohort in the UK. The use of twins in the study indicated that the association between the blood protein and a ten year decline in cognitive ability was independent of age and genetics, both of which are already known to affect the risk of developing Alzheimer's disease, the most common form of dementia.
The study, the largest of its kind, measured over 1,000 proteins in the blood of over 200 healthy individuals, using a laboratory test called a SOMAscan, a protein biomarker discovery tool which allows a high volume of proteins to be measured simultaneously. Using a computerised test, the researchers then assessed each individual's cognitive ability, and compared the results with the measured level of each protein in the blood.
For the first time, they found that the blood level of a protein called MAPKAPK5 was, on average, lower in individuals whose cognitive ability declined over a ten year period.
There are currently no treatments available proven to prevent Alzheimer's disease, and prevention trials for Alzheimer's disease can be problematic because to be effective, they must involve individuals at risk of the disease, who can be hard to identify. Studies using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) brain scans have been shown to display visible signs of the disease before the onset of symptoms, but these types of scans are both timely and costly.
To date, few other studies have looked at the blood of individuals with very early stages of cognitive declineand therefore most appropriate for a prevention study. Identifying blood markers such as MAPKAPK5, which may indicate a person's future risk of Alzheimer's disease, could contribute towards the better design of prevention trials.
Dr Steven Kiddle, lead author and Biostatistics Research Fellow at the MRC Social, Genetic & Developmental Psychiatry Centre at King's College London, said: 'Although we are still searching for an effective treatment for Alzheimer's disease, what we do know is that prevention of the disease is likely to be more effective than trying to reverse it.
'The next step will be to confirm whether or not our initial finding is specific for Alzheimer's disease, as this could lead to the development of a reliable blood test which would help clinicians identify suitable people forprevention trials.'
Read more:http://www.cusabio.com/catalog-13-1.html
The new research, published today in Translational Psychiatry, used data from over 100 sets of identical twins from TwinsUK, the biggest adult twin cohort in the UK. The use of twins in the study indicated that the association between the blood protein and a ten year decline in cognitive ability was independent of age and genetics, both of which are already known to affect the risk of developing Alzheimer's disease, the most common form of dementia.
The study, the largest of its kind, measured over 1,000 proteins in the blood of over 200 healthy individuals, using a laboratory test called a SOMAscan, a protein biomarker discovery tool which allows a high volume of proteins to be measured simultaneously. Using a computerised test, the researchers then assessed each individual's cognitive ability, and compared the results with the measured level of each protein in the blood.
For the first time, they found that the blood level of a protein called MAPKAPK5 was, on average, lower in individuals whose cognitive ability declined over a ten year period.
There are currently no treatments available proven to prevent Alzheimer's disease, and prevention trials for Alzheimer's disease can be problematic because to be effective, they must involve individuals at risk of the disease, who can be hard to identify. Studies using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) brain scans have been shown to display visible signs of the disease before the onset of symptoms, but these types of scans are both timely and costly.
To date, few other studies have looked at the blood of individuals with very early stages of cognitive declineand therefore most appropriate for a prevention study. Identifying blood markers such as MAPKAPK5, which may indicate a person's future risk of Alzheimer's disease, could contribute towards the better design of prevention trials.
Dr Steven Kiddle, lead author and Biostatistics Research Fellow at the MRC Social, Genetic & Developmental Psychiatry Centre at King's College London, said: 'Although we are still searching for an effective treatment for Alzheimer's disease, what we do know is that prevention of the disease is likely to be more effective than trying to reverse it.
'The next step will be to confirm whether or not our initial finding is specific for Alzheimer's disease, as this could lead to the development of a reliable blood test which would help clinicians identify suitable people forprevention trials.'
Read more:http://www.cusabio.com/catalog-13-1.html
2015年6月16日星期二
Human cell models accelerate research into brown fat
Since the 2009 discovery that energy-burning brown fat can be active in
adults, research has raced ahead to understand this tissue and exploit it to
treat the epidemic of obesity. Active brown fat also may assist in directly
easing the burden of diabetes and related metabolic diseases by lowering the
levels of glucose and fatty acids in the bloodstream. But progress in studying
human brown fat often has been slowed by difficulties in obtaining and studying
samples of the human cells that develop into brown fat.
Now, however, a team of researchers led by Yu-Hua Tseng, Ph.D., Investigator in the Section on Integrative Physiology and Metabolism at Joslin Diabetes Center and an Associate Professor of Medicine at Harvard Medical School, has created cell lines of human brown and white fat precursor cells that will help investigators to pick apart the factors that drive the development and activity of each type of cell.
"We can take human brown fat precursor cells, grow them in Petri dishes and then culture them to become energy-dissipating cells," says Dr. Tseng. "This cellular system provides a very important and exciting tool for understanding the biology of human brown fat tissue. It also offers a really nice system for drug screening."
The cell lines will allow scientists to study gene expression in precursor brown fat and white fat cells, and in the mature fat cells these cells create. Such analyses will improve our understanding of how brown fat cells develop and are regulated in the body -- and, potentially, how to transform the precursors of white fat cells into brown fat cells instead, says Dr. Tseng.
As the Joslin team reports in the journal Nature Medicine, the work began with taking samples of both brown and white precursor cells from four human subjects and genetically modifying these cells to "immortalize" them for long life in a Petri dish. The cells also were given a fluorescent marker to show activation of the UCP1 gene, the best known molecular indicator of how much energy a fat cell burns. The researchers then could induce the precursor cells to become mature fat cells and characterize the results.
After analyzing gene expression signatures in the precursor cells, the investigators demonstrated that they could reliably predict UCP1 expression in the resulting mature cells. They took an extra step to verify such predictions by examining the roles of two genes important in brown fat regulation known as PREX1 and EDRNB. When they used a genomic editing technique known as CRISPR/Cas9 to knock down the expression of these genes in precursor cells, the expression of UCP1 did indeed drop in the subsequent mature cells.
The scientists also found that a protein known as CD29 acts as a cell-surface marker for precursor fat cells that can generate mature cells with high energy potential, as shown by their UCP1 expression.
Detection of this CD29 marker eventually may help in selecting white fat precursor cells that can be transformed for obesity treatments, Dr. Tseng comments.
Using white fat tissue from liposuction or weight-loss surgery, "we might purify a population of these progenitor cells from an obese individual expressing C29 with high potential to become energy-dissipating cells," she explains. "We could purify these cells, expand them in vitro, turn them into brown fat cells and then put them back into the patient, and the patient wouldn't have to worry about immune rejection of these cells."
Previous studies had highlighted differences in brown fat metabolism between individuals and between various brown fat depots in an individual. Unsurprisingly, the latest research highlights this heterogeneity.
In one example, Dr. Tseng's group previously had shown that exposing precursor white fat cells to a protein known as BMP7 helps to spur the creation of brown fat cells. In analyses of the cell lines, precursor white fat cells from two subjects responded strongly to BMP7 but such cells from the other two subjects did not.
Despite such variations across individuals, Dr. Tseng emphasizes that her team's work underlines the high promise of energy-burning brown fat. "Our data eventually will help us to develop the best treatment for each patient," she says.
Read more:http://about.cusabio.com/m-208.html
Now, however, a team of researchers led by Yu-Hua Tseng, Ph.D., Investigator in the Section on Integrative Physiology and Metabolism at Joslin Diabetes Center and an Associate Professor of Medicine at Harvard Medical School, has created cell lines of human brown and white fat precursor cells that will help investigators to pick apart the factors that drive the development and activity of each type of cell.
"We can take human brown fat precursor cells, grow them in Petri dishes and then culture them to become energy-dissipating cells," says Dr. Tseng. "This cellular system provides a very important and exciting tool for understanding the biology of human brown fat tissue. It also offers a really nice system for drug screening."
The cell lines will allow scientists to study gene expression in precursor brown fat and white fat cells, and in the mature fat cells these cells create. Such analyses will improve our understanding of how brown fat cells develop and are regulated in the body -- and, potentially, how to transform the precursors of white fat cells into brown fat cells instead, says Dr. Tseng.
As the Joslin team reports in the journal Nature Medicine, the work began with taking samples of both brown and white precursor cells from four human subjects and genetically modifying these cells to "immortalize" them for long life in a Petri dish. The cells also were given a fluorescent marker to show activation of the UCP1 gene, the best known molecular indicator of how much energy a fat cell burns. The researchers then could induce the precursor cells to become mature fat cells and characterize the results.
After analyzing gene expression signatures in the precursor cells, the investigators demonstrated that they could reliably predict UCP1 expression in the resulting mature cells. They took an extra step to verify such predictions by examining the roles of two genes important in brown fat regulation known as PREX1 and EDRNB. When they used a genomic editing technique known as CRISPR/Cas9 to knock down the expression of these genes in precursor cells, the expression of UCP1 did indeed drop in the subsequent mature cells.
The scientists also found that a protein known as CD29 acts as a cell-surface marker for precursor fat cells that can generate mature cells with high energy potential, as shown by their UCP1 expression.
Detection of this CD29 marker eventually may help in selecting white fat precursor cells that can be transformed for obesity treatments, Dr. Tseng comments.
Using white fat tissue from liposuction or weight-loss surgery, "we might purify a population of these progenitor cells from an obese individual expressing C29 with high potential to become energy-dissipating cells," she explains. "We could purify these cells, expand them in vitro, turn them into brown fat cells and then put them back into the patient, and the patient wouldn't have to worry about immune rejection of these cells."
Previous studies had highlighted differences in brown fat metabolism between individuals and between various brown fat depots in an individual. Unsurprisingly, the latest research highlights this heterogeneity.
In one example, Dr. Tseng's group previously had shown that exposing precursor white fat cells to a protein known as BMP7 helps to spur the creation of brown fat cells. In analyses of the cell lines, precursor white fat cells from two subjects responded strongly to BMP7 but such cells from the other two subjects did not.
Despite such variations across individuals, Dr. Tseng emphasizes that her team's work underlines the high promise of energy-burning brown fat. "Our data eventually will help us to develop the best treatment for each patient," she says.
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2015年6月15日星期一
Scientists have discovered fossils of dinosaur remnants of red blood cells
In a discovery that could provide new insight into dinosaur physiology, and
may determine if certain species were warm-blooded or cold-blooded, a team of UK
researchers has discovered the remnants of red blood cells and connective tissue
in ancient fossils.
During the course of their work, experts from Imperial College London discovered tiny ovoid structures that had a denser inner-core, much like red blood cells, the British news outlet said. It also reported that the scientists found fibers with a banded structure, not unlike that in modern-day collagen in the ligaments and tendons of animals.
Soft tissues discovered in poorly-preserved fossils
While this not the first time that these types of soft tissues have been detected in dinosaur fossils, the previous reports came from unusually well-preserved specimen that suggested that they may have been contaminated in some way, study co-author Dr. Susannah Maidment told BBC News. In contrast, this study found soft tissues in poorly-preserved fossils.
In fact, Dr. Maidment said that these fossils had been lying around in the London Natural History Museum collections for more than a century, and described them as “scrappy, individual broken bones” from an unknown type of dinosaur. “If you’re finding soft tissues in these kinds of fossils, maybe this kind of preservation might be more common than we realized.”
Reports indicate that the structures appear to be genuine soft-tissue remains that have not been fossilized, and that chemical analysis of the suspected collagen protein(http://www.cusabio.com/catalog-13-1.html) and red blood cells was carried out with a mass spectrometer. That analysis revealed fragments of what appear to be the building blocks of proteins known as amino acids, and the chemical profile of the cells looked similar to those of an emu, a direct descendent of dinosaurs, the authors explained.
Analysis may determine which dinosaurs are related, warm-blooded
In vertebrates, creatures with smaller red blood cells have faster metabolic rates and tend to be warm blooded, and creatures with larger ones have slower metabolic rates and are typically cold blooded, Dr. Maidment told BBC News. While experts are not certain if this is true in dinosaurs, they may be able to find out if they can start finding red blood cells of various species.
Similarly, by studying the apparent collagen fibers, the research team may be able to learn more about the relationships between different dinosaur species. Using a technique known as collagen fingerprinting, which is based on the notion that the structure of an animal’s collage molecule is unique to that creature, they could determine which dinosaurs are related to each other.
“We still need to do more research to confirm what it is that we are imaging in these dinosaur bone fragments,” co-author Dr. Sergio Bertazzo added, “[but] if we can confirm that our initial observations are correct, then this could yield fresh insights into how these creatures once lived and evolved.”
During the course of their work, experts from Imperial College London discovered tiny ovoid structures that had a denser inner-core, much like red blood cells, the British news outlet said. It also reported that the scientists found fibers with a banded structure, not unlike that in modern-day collagen in the ligaments and tendons of animals.
Soft tissues discovered in poorly-preserved fossils
While this not the first time that these types of soft tissues have been detected in dinosaur fossils, the previous reports came from unusually well-preserved specimen that suggested that they may have been contaminated in some way, study co-author Dr. Susannah Maidment told BBC News. In contrast, this study found soft tissues in poorly-preserved fossils.
In fact, Dr. Maidment said that these fossils had been lying around in the London Natural History Museum collections for more than a century, and described them as “scrappy, individual broken bones” from an unknown type of dinosaur. “If you’re finding soft tissues in these kinds of fossils, maybe this kind of preservation might be more common than we realized.”
Reports indicate that the structures appear to be genuine soft-tissue remains that have not been fossilized, and that chemical analysis of the suspected collagen protein(http://www.cusabio.com/catalog-13-1.html) and red blood cells was carried out with a mass spectrometer. That analysis revealed fragments of what appear to be the building blocks of proteins known as amino acids, and the chemical profile of the cells looked similar to those of an emu, a direct descendent of dinosaurs, the authors explained.
Analysis may determine which dinosaurs are related, warm-blooded
In vertebrates, creatures with smaller red blood cells have faster metabolic rates and tend to be warm blooded, and creatures with larger ones have slower metabolic rates and are typically cold blooded, Dr. Maidment told BBC News. While experts are not certain if this is true in dinosaurs, they may be able to find out if they can start finding red blood cells of various species.
Similarly, by studying the apparent collagen fibers, the research team may be able to learn more about the relationships between different dinosaur species. Using a technique known as collagen fingerprinting, which is based on the notion that the structure of an animal’s collage molecule is unique to that creature, they could determine which dinosaurs are related to each other.
“We still need to do more research to confirm what it is that we are imaging in these dinosaur bone fragments,” co-author Dr. Sergio Bertazzo added, “[but] if we can confirm that our initial observations are correct, then this could yield fresh insights into how these creatures once lived and evolved.”
New technology to help diagnose breast cancer by urine
Recently, published in the international journal BMC Cancer research paper, the researchers from the University of Freiburg by the research and development of a new technology, which can analyze the urine sample to help detect breast cancer, this method can determining the level of microRNAs molecules that regulate cell metabolism, which is usually offset levels of microRNAs in cancer cells; by determining the composition of the urine microRNAs, researchers can make the success rate of this technique diagnosis of breast cancer is 91%.
The world there are about 1.7 million women suffering from breast cancer, while breast cancer is one of the common female cancer, the disease will cause more than 52 million deaths each year, but until now researchers have generally through breast x-ray tomography or ultrasound Check to make diagnosis of breast cancer tissue, but due to exposure to radiation exposure of breast tissue will usually make a lot of patients with recurrent disease.
In this paper, the researchers developed the new technique by using urine samples can be checked for breast cancer, the technology has changed based on patient metabolism, researchers urine of nine kinds of microRNAs determine the concentration of molecules, and molecules microRNAs You can regulate the metabolism of cells, compared to healthy samples and disease samples, the researchers found that there are four kinds of microRNAs levels showed significant differences.
Professor Stickeler noted that the urine of patients with breast cancer microRNA characteristics can be specifically modified so microRNAs, or can help us with breast cancer screening, and of course with the help of microRNA characteristics under study to develop technology also has 91% diagnostic accuracy. Currently researchers have patented the technology, they encourage more women to take advantage of this new technology for the early diagnosis of breast cancer, after making a diagnosis, the patient's malignant tissue will be removed by surgery, not as Over the past doctors would remove the entire breast tissue of a patient, the late researcher hopes more research is needed to optimize the improvement of this new technology so that it can be better for human health services.
More details:http://www.cusabio.com/catalog-16-1.html
The world there are about 1.7 million women suffering from breast cancer, while breast cancer is one of the common female cancer, the disease will cause more than 52 million deaths each year, but until now researchers have generally through breast x-ray tomography or ultrasound Check to make diagnosis of breast cancer tissue, but due to exposure to radiation exposure of breast tissue will usually make a lot of patients with recurrent disease.
In this paper, the researchers developed the new technique by using urine samples can be checked for breast cancer, the technology has changed based on patient metabolism, researchers urine of nine kinds of microRNAs determine the concentration of molecules, and molecules microRNAs You can regulate the metabolism of cells, compared to healthy samples and disease samples, the researchers found that there are four kinds of microRNAs levels showed significant differences.
Professor Stickeler noted that the urine of patients with breast cancer microRNA characteristics can be specifically modified so microRNAs, or can help us with breast cancer screening, and of course with the help of microRNA characteristics under study to develop technology also has 91% diagnostic accuracy. Currently researchers have patented the technology, they encourage more women to take advantage of this new technology for the early diagnosis of breast cancer, after making a diagnosis, the patient's malignant tissue will be removed by surgery, not as Over the past doctors would remove the entire breast tissue of a patient, the late researcher hopes more research is needed to optimize the improvement of this new technology so that it can be better for human health services.
More details:http://www.cusabio.com/catalog-16-1.html
2015年6月12日星期五
Immune cells reveal "secret agent 007" is the manufacturing process
Recently, an article published in the international journal Nature Immunology research papers, there are scientists who study reveals the immune cells by "spy 007" is manufactured in the process, or to clarify how the immune system protects the body against disease provide some help.
Dendritic cells are a rich source of wisdom immune cells, which can gather a lot of information on viruses, bacteria, fungi, cancer and to help the immune system resist disease invasion, and understand how they are manufactured to generate dendritic cells may help scientists develop new ways to enhance the body's immune response against infection. Scientists say that dendritic cells can "educate" the immune system, it will tell against infected T cells and NK cells viruses, bacteria, fungi or cancer looks like, so that these cells can be targeted to kill the intruders.
If we learn how to control dendritic cells, then we might enhance their immune response against infection, or autoimmune diseases decreased damage to the body. For this study, researchers used the latest technology to detect a single immune cells and their progeny, and found that for all subsets of dendritic cells and not in terms of their so-called single progeny, but for each but there are subtypes of cells only special progenitor cells. Targeting progenitor cells may help develop new therapies against a variety of infections, a progenitor cell can be made to produce a plurality of daughter cells, and progenitor cells to produce a variety of inhibiting dendritic cell subsets may sometimes be effective in treating a variety of self-help immune diseases. Similarly, special dendritic cells induce additional generation might improve the immune response of the body to resist infection or a vaccine.
Finally, the researchers say, the evolutionary family tree draws blood cells may help understand the mechanisms of disease, and the body of each of the blood and immune cells are made of blood stem cells from the differentiation and development. So tracking evolutionary tree can be found starting each type cells, but also can explain how parental cell determines the direction of the next step of development. By analyzing the genetic characteristics of different cells, researchers can look for to treat a range of infectious diseases, cancer and immune disorders and other diseases of the new targets.
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2015年6月11日星期四
Methods for the treatment of "iron overload" syndrome
A form of the hereditary disease is inherited blood disease.Not everyone
who would have inherited genes have to the disease, but those who do, gene from
both parents genetic defects.Inherited blood disease is in the northern
europeans find the most common people.
Over the past few years, those with diseases will see too much iron in the liver, heart, pancreas, joint and the pituitary gland, lead to health problems, such as liver cirrhosis, liver cancer, diabetes, heart disease and joint disease.And disease can get their blood routine to get rid of the excess iron.
"Over the past 150 years, we don't know how iron has been adopted by the liver - how to get there," Mitchell Knudsen, associate professor of food science and human nutrition ufida said."We know there is put it into a protein to the liver. However, no one knows what the protein, it is such a fundamental problem, people just don't know the answer."
Scientists now know, this is ZIP14 protein.
Published online in the journal of the cell metabolism, a new study on 28th knutson and his colleagues found that mice lacking ZIP14 - when mating with mice blood disease - no load of iron in the liver.
As the new found that scientists can design drugs targeted ZIP14 prevent iron from loading in the liver.Such drugs, however, will need to use a combination of combination of drugs and to remove iron from the body currently, knutson described below.
Although scientists found that the progress of the hemochromatosis, not disorderly already has a relatively simple process: bloodletting.But Knudsen do see the findings as more relevant iron overload may treat other difficult and complicated diseases, such as the Mediterranean anemia.The Mediterranean anemia patients cannot make healthy red blood cells, so need regular blood transfusion to maintain life.
Blood transfusion is introduced into the large amounts of iron in the blood, thus rapidly to the liver.If can prevent liver iron load - through methods such as blocking ZIP14 - it will be easier to get in the extra iron in the blood drug from the body.
More content:http://www.cusabio.com/catalog-13-1.html
Over the past few years, those with diseases will see too much iron in the liver, heart, pancreas, joint and the pituitary gland, lead to health problems, such as liver cirrhosis, liver cancer, diabetes, heart disease and joint disease.And disease can get their blood routine to get rid of the excess iron.
"Over the past 150 years, we don't know how iron has been adopted by the liver - how to get there," Mitchell Knudsen, associate professor of food science and human nutrition ufida said."We know there is put it into a protein to the liver. However, no one knows what the protein, it is such a fundamental problem, people just don't know the answer."
Scientists now know, this is ZIP14 protein.
Published online in the journal of the cell metabolism, a new study on 28th knutson and his colleagues found that mice lacking ZIP14 - when mating with mice blood disease - no load of iron in the liver.
As the new found that scientists can design drugs targeted ZIP14 prevent iron from loading in the liver.Such drugs, however, will need to use a combination of combination of drugs and to remove iron from the body currently, knutson described below.
Although scientists found that the progress of the hemochromatosis, not disorderly already has a relatively simple process: bloodletting.But Knudsen do see the findings as more relevant iron overload may treat other difficult and complicated diseases, such as the Mediterranean anemia.The Mediterranean anemia patients cannot make healthy red blood cells, so need regular blood transfusion to maintain life.
Blood transfusion is introduced into the large amounts of iron in the blood, thus rapidly to the liver.If can prevent liver iron load - through methods such as blocking ZIP14 - it will be easier to get in the extra iron in the blood drug from the body.
More content:http://www.cusabio.com/catalog-13-1.html
2015年6月9日星期二
Extend the life of the password, the discovery of new DNA bases
Almost all life on the earth's DNA genetic code is composed of four nucleotides with different bases, they are connected through the arrangement and distorted form a double helix structure.Recently, a team of scientists from the United States found that two new nucleotide with other connection arrangement form a double helix structure, this new discovery can be used for medical USES a new protein synthesis.
Synthetic biologists over the years has been trying to expand the nature of the genetic "letters" sequence.The composition of nucleotide bases cytosine and guanine and adenine and thymine respectively by the letter "C", "G", "A" and "T" said.But so far, the efforts to little effect.For example, some new base pairs but can't form a spiral structure, this limits the possibility of its integrated into the natural DNA structure.Millie m. Georgiadis where the team want to try to see another potential of the letter "Z" (6 - amino - 5 - nitro - 2 - (1 h) pyridone) and "P" (2 - amino - imidazo [1, 2 - a] 1,3,5 triazin - 4 (8 h) one), will form a spiral structure and evolution.
, the researchers found that multiple ZP can form a double helix structure, like CG and AT the same, but also possess a natural DNA needed to complete the biological function of flexible and rigid combination of same.ZP to form the big groove width than the GC to increased 1, in addition with GC is very similar to other properties.ZP were shown, the team also can integrate well with the traditional genome, which owns six DNA "letters" GACTZP can evolve.
These results have a far-reaching influence on synthetic biology, as the standard added two nucleotides of DNA.That create extensions can also be used for DNA polymerase, ligase, kinase and other enzyme reaction.They can also through the platform to create a new function of molecular evolution in vitro, eventually operate in living cells.Perhaps as a "generic" part, nitro can be introduced in multiple sites and shall not affect the geometry of DNA.This makes natural polymerase can effectively search sequence of DNA "letters" of the space.Finally, these results indicate that the conformation of DNA has a natural DNA containing ZP nucleotide plasticity, the plasticity might be in it is very important for the complete biological functions in living cells.
Read more：http://www.cusabio.com/
Synthetic biologists over the years has been trying to expand the nature of the genetic "letters" sequence.The composition of nucleotide bases cytosine and guanine and adenine and thymine respectively by the letter "C", "G", "A" and "T" said.But so far, the efforts to little effect.For example, some new base pairs but can't form a spiral structure, this limits the possibility of its integrated into the natural DNA structure.Millie m. Georgiadis where the team want to try to see another potential of the letter "Z" (6 - amino - 5 - nitro - 2 - (1 h) pyridone) and "P" (2 - amino - imidazo [1, 2 - a] 1,3,5 triazin - 4 (8 h) one), will form a spiral structure and evolution.
, the researchers found that multiple ZP can form a double helix structure, like CG and AT the same, but also possess a natural DNA needed to complete the biological function of flexible and rigid combination of same.ZP to form the big groove width than the GC to increased 1, in addition with GC is very similar to other properties.ZP were shown, the team also can integrate well with the traditional genome, which owns six DNA "letters" GACTZP can evolve.
These results have a far-reaching influence on synthetic biology, as the standard added two nucleotides of DNA.That create extensions can also be used for DNA polymerase, ligase, kinase and other enzyme reaction.They can also through the platform to create a new function of molecular evolution in vitro, eventually operate in living cells.Perhaps as a "generic" part, nitro can be introduced in multiple sites and shall not affect the geometry of DNA.This makes natural polymerase can effectively search sequence of DNA "letters" of the space.Finally, these results indicate that the conformation of DNA has a natural DNA containing ZP nucleotide plasticity, the plasticity might be in it is very important for the complete biological functions in living cells.
Read more：http://www.cusabio.com/
2015年6月5日星期五
Using the method of DNA extraction kit
[The genomic DNA extracted from cultured cells]
When using the suspension culture of animal cells:
(1) using the Collection Tube Collection 1 x 105 ~ 1.5 x 107 cell suspension, 5000 RPM centrifuge for 5 minutes, abandon supernatant (cell culture).
(2) to join 150 mu l sterilized distilled water or PBS suspension cells.
(3) to join 500 mu l Solution A and 0.8 mu l RNase A1, intense oscillation for 15 seconds, and then let stand at room temperature for 1 minute.
When using the adherent cells:
(1) that all cultures, to join 650 mu l Solution in A petri dish A, let stand at room temperature for 1 minute.
) 96 orifice plate and so on each hole one hold 650 mu l solution, please fractional processing cell.
(2) with pipetting gun head blown adherent culture cell, take 650 mu l cell suspension was transferred to the Collection Tube.
(3) add 0.8 mu l RNase A1, intense oscillation for 15 seconds, and then let stand at room temperature for 1 minute.
2. Add in 400 mu l Solution B, oscillation mix.
3. Add 1 ml of 4 ℃ precooling Solution C, after thoroughly incorporated, 12000 RPM centrifugal 2 minutes.
4. Left to the upper organic phase, add 1 ml of 4 ℃ precooling Solution C, after thoroughly incorporated, 12000 RPM centrifugal 2 minutes.
5. Left to the upper organic phase, and then transferring aqueous solution (colorless below) to put the Collection Tube Filter on the Cup, 12000 RPM centrifugal for 1 minute.
Note) organic phase (upper) with color, please be sure to do, otherwise it will hinder the DNA binding to DNA preparation of membrane. Interphase precipitation don't have to consider, when the filter will be removed.
6. Put the Filter Cup, add 400 mu in the filtrate l DB Buffer, mixed evenly.
7. The kit http://www.cusabio.com/catalog-10-1.html of the Spin Column to Collection Tube. The above operation 6 mixture transfer to Spin Column, 12000 RPM centrifugal 1 minute, abandon the filtrate.
8. 500 mu l Rinse A join to Spin Column, 12000 RPM centrifugal 30 seconds, abandon the filtrate.
9. 700 mu of Rinse B l join to Spin Column, 12000 RPM centrifugal 30 seconds, abandon the filtrate.
Note) along the Spin around the Column wall to join the Rinse B, this helps to completely flush cleave in the salt on the wall.
10. Repeat steps 9.
11. Will Spin Column placed on the new 1.5 ml centrifuge tube, the Spin of the Column membrane sterilization of the central place in 50 ~ 200 mu l distilled water or Elution Buffer, and let stand at room temperature for 1 minute.
Note) the sterilized distilled water or Elution Buffer when heated to 65 ℃ is used to improve the efficiency of Elution.
12. 12, 000 RPM centrifugal 1 minute elution DNA.
2015年6月2日星期二
HIV also love to eat sweets
A new study from Northwestern University Feinberg School of Medicine and Vanderbilt University found that HIV craving sweets, which became one of its fatal weakness.
To activate immune cells invade to go after it in the desire to get the virus from the cells of the sugar and nutrients to achieve replication and push it growing wild in the body.
Scientists have found that immune cells turn on sugar and nutrient rich pipeline of switches. Then they used an experimental compound to block the switch, shut down the pipeline, thereby starving HIV. The virus can not replicate in human cells in vitro.
This finding may also be used in the treatment of cancer, the cancer is well known that cells in the sugar and other nutrients also has a great demand for these materials it needs to achieve growth and spread.
However, until now, no one knows to signal to the newly activated T cells, asking them to step in repairing the sugar and other nutrients. These nutrients will become cellular and viral genetic material required for the growth component.
Northwestern University Feinberg School of Medicine and Vanderbilt University scientists have stated, the first step in T cell to the pantry in stock, involving open a called phospholipase D1 (PLD1) cell components. Then they used an experimental compound to block PLD1, shut down the pipeline.
The study found that this compound may also slow down the abnormal activation of immune cell proliferation. Some current HIV drugs can prevent HIV growth, but it will not affect HIV touched abnormal excessive activation of immune cells and growth.
Excessive immune cell growth is considered to contribute to the lifelong persistence of HIV, leading to excessive inflammation caused premature organ damage in patients with HIV - even when live virus suppression in current drugs.
When HIV enters the bloodstream, it will look to the commander in chief of the immune system - activated CD4 + T cells. These activated cells already in the blood of other pathogens or allergens responded, being mad food glucose and amino acids from the blood, they need these substances to produce DNA components. Cell factories operating at full capacity to produce these components to produce soldiers.
Before cancer cells are addicted to sugar added to Northwestern University in 2012, Taylor was a teacher at Vanderbilt University. Taylor knew his colleagues at Vanderbilt University mass screening of breast cancer cells blocked the growth potential drug discovered a compound. This compound PLD1 prevented by blocking the growth of breast cancer cells. Taylor and his colleagues wondered whether the same block in Antibody service http://about.cusabio.com/m-186.html to block HIV enzyme can utilize nutrient supply to the cells, inhibit the invasion of HIV.
Their work confirms this. In vitro, this complex was cut off glucose and other nutrients, preventing the HIV DNA construct sufficient to generate its genetic material required for replication.
To activate immune cells invade to go after it in the desire to get the virus from the cells of the sugar and nutrients to achieve replication and push it growing wild in the body.
Scientists have found that immune cells turn on sugar and nutrient rich pipeline of switches. Then they used an experimental compound to block the switch, shut down the pipeline, thereby starving HIV. The virus can not replicate in human cells in vitro.
This finding may also be used in the treatment of cancer, the cancer is well known that cells in the sugar and other nutrients also has a great demand for these materials it needs to achieve growth and spread.
However, until now, no one knows to signal to the newly activated T cells, asking them to step in repairing the sugar and other nutrients. These nutrients will become cellular and viral genetic material required for the growth component.
Northwestern University Feinberg School of Medicine and Vanderbilt University scientists have stated, the first step in T cell to the pantry in stock, involving open a called phospholipase D1 (PLD1) cell components. Then they used an experimental compound to block PLD1, shut down the pipeline.
The study found that this compound may also slow down the abnormal activation of immune cell proliferation. Some current HIV drugs can prevent HIV growth, but it will not affect HIV touched abnormal excessive activation of immune cells and growth.
Excessive immune cell growth is considered to contribute to the lifelong persistence of HIV, leading to excessive inflammation caused premature organ damage in patients with HIV - even when live virus suppression in current drugs.
When HIV enters the bloodstream, it will look to the commander in chief of the immune system - activated CD4 + T cells. These activated cells already in the blood of other pathogens or allergens responded, being mad food glucose and amino acids from the blood, they need these substances to produce DNA components. Cell factories operating at full capacity to produce these components to produce soldiers.
Before cancer cells are addicted to sugar added to Northwestern University in 2012, Taylor was a teacher at Vanderbilt University. Taylor knew his colleagues at Vanderbilt University mass screening of breast cancer cells blocked the growth potential drug discovered a compound. This compound PLD1 prevented by blocking the growth of breast cancer cells. Taylor and his colleagues wondered whether the same block in Antibody service http://about.cusabio.com/m-186.html to block HIV enzyme can utilize nutrient supply to the cells, inhibit the invasion of HIV.
Their work confirms this. In vitro, this complex was cut off glucose and other nutrients, preventing the HIV DNA construct sufficient to generate its genetic material required for replication.
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