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Method captures images of multiple cell components
(green), mitochondria (purple),
Golgi apparatus (red), and
peroxisomes (yellow) in a cell
Credit: Maier Avendano
A new microscopy method allows scientists to image many cellular components at once, according to a paper published in Nature Methods.
Such images could shed light on complex cellular pathways and might lead to new ways to diagnose disease, track its progress, or monitor treatment effectiveness at a cellular level, the researchers said.
They noted that today’s imaging methods typically spot, at most, 3 or 4 types of biomolecules simultaneously.
But to truly understand complex cellular functions, it’s important to be able to visualize most or all of the molecules at once, said study author Peng Yin, PhD, of the Wyss Institute at Harvard Medical School in Boston.
“If you can see only a few things at a time, you are missing the big picture,” Dr Yin said.
So he and his colleagues sought a way to take aerial views of cells that could show dozens of types of biomolecules. They decided to build upon a method called DNA-PAINT, which can create snapshots of up to 3 molecules at once by labeling them with different colored dyes.
The team modified DNA-PAINT to create a method called Exchange-PAINT. Exchange-PAINT relies on the fact that DNA strands with the correct sequence of nucleotides bind specifically to partner strands with complementary sequences.
The researchers label a biomolecule they want to visualize with a short DNA tag. Then, they add to the solution a partner strand carrying a fluorescent dye that lights up only when the 2 strands pair up.
When that partner strand binds the tagged biomolecule, it lights up, then lets go, causing the biomolecule to “blink” at a precise rate the researchers can control. The team uses this blinking to obtain ultra-sharp images.
They repeat the process to visualize a second target, a third, and so on. Then, they overlay the resulting images to create a composite image in which each biomolecule is assigned a different color.
This allows them to create false-color images that simultaneously show many types of biomolecules—far more than they could simultaneously visualize by labeling them with different colored dyes. And these false-color images allow them to spot enough biomolecules at once to capture the entire scene.
To test Exchange-PAINT, the researchers created 10 unique pieces of folded DNA that resembled the numerals 0 through 9. These numerals could be resolved with less than 10 nanometers resolution, or 1/20th of the diffraction limit.
The team was able to use Exchange-PAINT to capture clear images of the 10 different DNA origami structures in one image. They also used the method to capture images of fixed human cells, with each color tagging a different cellular component—microtubules, mitochondria, Golgi apparatus, or peroxisomes.
Dr Yin expects that, with further development, this method could be used to visualize dozens of cellular components at once. 
(green), mitochondria (purple),
Golgi apparatus (red), and
peroxisomes (yellow) in a cell
Credit: Maier Avendano
A new microscopy method allows scientists to image many cellular components at once, according to a paper published in Nature Methods.
Such images could shed light on complex cellular pathways and might lead to new ways to diagnose disease, track its progress, or monitor treatment effectiveness at a cellular level, the researchers said.
They noted that today’s imaging methods typically spot, at most, 3 or 4 types of biomolecules simultaneously.
But to truly understand complex cellular functions, it’s important to be able to visualize most or all of the molecules at once, said study author Peng Yin, PhD, of the Wyss Institute at Harvard Medical School in Boston.
“If you can see only a few things at a time, you are missing the big picture,” Dr Yin said.
So he and his colleagues sought a way to take aerial views of cells that could show dozens of types of biomolecules. They decided to build upon a method called DNA-PAINT, which can create snapshots of up to 3 molecules at once by labeling them with different colored dyes.
The team modified DNA-PAINT to create a method called Exchange-PAINT. Exchange-PAINT relies on the fact that DNA strands with the correct sequence of nucleotides bind specifically to partner strands with complementary sequences.
The researchers label a biomolecule they want to visualize with a short DNA tag. Then, they add to the solution a partner strand carrying a fluorescent dye that lights up only when the 2 strands pair up.
When that partner strand binds the tagged biomolecule, it lights up, then lets go, causing the biomolecule to “blink” at a precise rate the researchers can control. The team uses this blinking to obtain ultra-sharp images.
They repeat the process to visualize a second target, a third, and so on. Then, they overlay the resulting images to create a composite image in which each biomolecule is assigned a different color.
This allows them to create false-color images that simultaneously show many types of biomolecules—far more than they could simultaneously visualize by labeling them with different colored dyes. And these false-color images allow them to spot enough biomolecules at once to capture the entire scene.
To test Exchange-PAINT, the researchers created 10 unique pieces of folded DNA that resembled the numerals 0 through 9. These numerals could be resolved with less than 10 nanometers resolution, or 1/20th of the diffraction limit.
The team was able to use Exchange-PAINT to capture clear images of the 10 different DNA origami structures in one image. They also used the method to capture images of fixed human cells, with each color tagging a different cellular component—microtubules, mitochondria, Golgi apparatus, or peroxisomes.
Dr Yin expects that, with further development, this method could be used to visualize dozens of cellular components at once.
(green), mitochondria (purple),
Golgi apparatus (red), and
peroxisomes (yellow) in a cell
Credit: Maier Avendano
A new microscopy method allows scientists to image many cellular components at once, according to a paper published in Nature Methods.
Such images could shed light on complex cellular pathways and might lead to new ways to diagnose disease, track its progress, or monitor treatment effectiveness at a cellular level, the researchers said.
They noted that today’s imaging methods typically spot, at most, 3 or 4 types of biomolecules simultaneously.
But to truly understand complex cellular functions, it’s important to be able to visualize most or all of the molecules at once, said study author Peng Yin, PhD, of the Wyss Institute at Harvard Medical School in Boston.
“If you can see only a few things at a time, you are missing the big picture,” Dr Yin said.
So he and his colleagues sought a way to take aerial views of cells that could show dozens of types of biomolecules. They decided to build upon a method called DNA-PAINT, which can create snapshots of up to 3 molecules at once by labeling them with different colored dyes.
The team modified DNA-PAINT to create a method called Exchange-PAINT. Exchange-PAINT relies on the fact that DNA strands with the correct sequence of nucleotides bind specifically to partner strands with complementary sequences.
The researchers label a biomolecule they want to visualize with a short DNA tag. Then, they add to the solution a partner strand carrying a fluorescent dye that lights up only when the 2 strands pair up.
When that partner strand binds the tagged biomolecule, it lights up, then lets go, causing the biomolecule to “blink” at a precise rate the researchers can control. The team uses this blinking to obtain ultra-sharp images.
They repeat the process to visualize a second target, a third, and so on. Then, they overlay the resulting images to create a composite image in which each biomolecule is assigned a different color.
This allows them to create false-color images that simultaneously show many types of biomolecules—far more than they could simultaneously visualize by labeling them with different colored dyes. And these false-color images allow them to spot enough biomolecules at once to capture the entire scene.
To test Exchange-PAINT, the researchers created 10 unique pieces of folded DNA that resembled the numerals 0 through 9. These numerals could be resolved with less than 10 nanometers resolution, or 1/20th of the diffraction limit.
The team was able to use Exchange-PAINT to capture clear images of the 10 different DNA origami structures in one image. They also used the method to capture images of fixed human cells, with each color tagging a different cellular component—microtubules, mitochondria, Golgi apparatus, or peroxisomes.
Dr Yin expects that, with further development, this method could be used to visualize dozens of cellular components at once.
ASCO explains how ACA impacts trial participation
patient and her father
Credit: Rhoda Baer
The Affordable Care Act (ACA) includes provisions that may make it easier for US cancer patients to participate in clinical trials.
But this aspect of the law has not received much attention and is not well understood, according to the American Society of Clinical Oncology (ASCO).
So the organization has created educational materials for providers and patients that explain ACA coverage as it relates to clinical trials.
“ASCO and other groups fought long and hard for this law requiring insurers nationwide to cover the routine costs of care for individuals participating in clinical trials,” said ASCO President Clifford A. Hudis, MD, FACP.
“Healthcare providers, financial counselors, and others involved in helping patients need to understand the law’s provisions so that their patients can benefit and we can make scientific progress.”
The law, which is effective for health plans newly issued or renewed after January 1, 2014, prohibits health plans or insurance issuers from:
- Denying participation of beneficiaries in clinical trials
- Denying or limiting coverage of routine patient care costs, subject to the plan’s out-of-network coverage policy
- Discriminating against the individual on the basis of participation in a trial.
The federal government has not yet issued regulations to guide implementation of the law. While much of the statutory language is clear, in the absence of federal guidance, payers will likely vary on the legal interpretation of each element of the provision.
Therefore, understanding the provisions can help patients and their healthcare providers seek the best available treatment options, which may include participation in a clinical trial.
Provider materials are available on ASCO’s Clinical Trials Coverage web page at www.ASCO.org/ClinicalTrialsCoverage.
Patient materials available on Cancer.Net include a detailed article explaining health insurance coverage of clinical trials at www.cancer.net/clinicaltrials and a fact sheet that provides an overview of the ACA provision at www.cancer.net/factsheets.
patient and her father
Credit: Rhoda Baer
The Affordable Care Act (ACA) includes provisions that may make it easier for US cancer patients to participate in clinical trials.
But this aspect of the law has not received much attention and is not well understood, according to the American Society of Clinical Oncology (ASCO).
So the organization has created educational materials for providers and patients that explain ACA coverage as it relates to clinical trials.
“ASCO and other groups fought long and hard for this law requiring insurers nationwide to cover the routine costs of care for individuals participating in clinical trials,” said ASCO President Clifford A. Hudis, MD, FACP.
“Healthcare providers, financial counselors, and others involved in helping patients need to understand the law’s provisions so that their patients can benefit and we can make scientific progress.”
The law, which is effective for health plans newly issued or renewed after January 1, 2014, prohibits health plans or insurance issuers from:
- Denying participation of beneficiaries in clinical trials
- Denying or limiting coverage of routine patient care costs, subject to the plan’s out-of-network coverage policy
- Discriminating against the individual on the basis of participation in a trial.
The federal government has not yet issued regulations to guide implementation of the law. While much of the statutory language is clear, in the absence of federal guidance, payers will likely vary on the legal interpretation of each element of the provision.
Therefore, understanding the provisions can help patients and their healthcare providers seek the best available treatment options, which may include participation in a clinical trial.
Provider materials are available on ASCO’s Clinical Trials Coverage web page at www.ASCO.org/ClinicalTrialsCoverage.
Patient materials available on Cancer.Net include a detailed article explaining health insurance coverage of clinical trials at www.cancer.net/clinicaltrials and a fact sheet that provides an overview of the ACA provision at www.cancer.net/factsheets.
patient and her father
Credit: Rhoda Baer
The Affordable Care Act (ACA) includes provisions that may make it easier for US cancer patients to participate in clinical trials.
But this aspect of the law has not received much attention and is not well understood, according to the American Society of Clinical Oncology (ASCO).
So the organization has created educational materials for providers and patients that explain ACA coverage as it relates to clinical trials.
“ASCO and other groups fought long and hard for this law requiring insurers nationwide to cover the routine costs of care for individuals participating in clinical trials,” said ASCO President Clifford A. Hudis, MD, FACP.
“Healthcare providers, financial counselors, and others involved in helping patients need to understand the law’s provisions so that their patients can benefit and we can make scientific progress.”
The law, which is effective for health plans newly issued or renewed after January 1, 2014, prohibits health plans or insurance issuers from:
- Denying participation of beneficiaries in clinical trials
- Denying or limiting coverage of routine patient care costs, subject to the plan’s out-of-network coverage policy
- Discriminating against the individual on the basis of participation in a trial.
The federal government has not yet issued regulations to guide implementation of the law. While much of the statutory language is clear, in the absence of federal guidance, payers will likely vary on the legal interpretation of each element of the provision.
Therefore, understanding the provisions can help patients and their healthcare providers seek the best available treatment options, which may include participation in a clinical trial.
Provider materials are available on ASCO’s Clinical Trials Coverage web page at www.ASCO.org/ClinicalTrialsCoverage.
Patient materials available on Cancer.Net include a detailed article explaining health insurance coverage of clinical trials at www.cancer.net/clinicaltrials and a fact sheet that provides an overview of the ACA provision at www.cancer.net/factsheets.
Researcher status affects paper popularity, study suggests
Credit: Rhoda Baer
New research indicates that author status affects how frequently scientific papers are cited, but the size of that effect depends on a number of other factors.
Investigators found that, overall, citations increased 12% above the expected level when authors were awarded “prestigious investigator status” at the Howard Hughes Medical Institute (HHMI).
However, certain kinds of research papers benefitted more than others by this increased prestige.
“We find much more of an effect on recent papers published in a short window before the prize,” said study author Pierre Azoulay, PhD, of the MIT Sloan School of Management in Cambridge.
And the greatest gains came for papers in new areas of research and for papers published in lower-profile journals. Younger researchers who had lower profiles prior to receiving the HHMI award were more likely to see a change as well.
“The effect was much more pronounced when there was more reason to be uncertain about the quality of the science or the scientist before the prize,” Dr Azoulay noted.
This paper, titled “Matthew: Effect or Fable?,” was published in Management Science.
The “Matthew Effect” is a term coined by sociologist Robert K. Merton to describe the possibility that the work of those with high status receives greater attention than equivalent work by those who are not as well known.
Positively identifying this phenomenon in scientific paper citations is difficult, however, because it is hard to separate the status of the author from the quality of the paper. It is possible, after all, that better-known researchers are simply producing higher-quality papers, which get more attention as a result.
But Dr Azoulay and his colleagues said they’ve found a way to address this issue. They looked at papers first published before the authors became HHMI investigators, then examined the citation rates for those papers after the HHMI appointments occurred, compared to a baseline of similar papers whose authors did not receive HHMI appointments.
More specifically, each paper in the study was paired with what Dr Azoulay called a “fraternal twin,” that is, another paper published in the same journal, at the same time, with the same initial citation pattern. For good measure, the authors of the papers in this comparison group were all scientists who had received other early career awards.
In all, from 1984 through 2003, 443 scientists were named HHMI investigators. Dr Azoulay and his colleagues examined 3636 papers written by 424 of those scientists, comparing them to 3636 papers in the control group.
“You couldn’t tell [the 2 sets of papers] apart in terms of citation trajectories, up until the time of the prize,” Dr Azoulay said.
Beyond the overall 12% increase in citations, the effect was nearly twice as great for papers published in lower-profile journals.
Alternately, Dr Azoulay pointed out, “If your paper was published in Cell or Nature or Science, the HHMI [award] doesn’t add a lot.”
Credit: Rhoda Baer
New research indicates that author status affects how frequently scientific papers are cited, but the size of that effect depends on a number of other factors.
Investigators found that, overall, citations increased 12% above the expected level when authors were awarded “prestigious investigator status” at the Howard Hughes Medical Institute (HHMI).
However, certain kinds of research papers benefitted more than others by this increased prestige.
“We find much more of an effect on recent papers published in a short window before the prize,” said study author Pierre Azoulay, PhD, of the MIT Sloan School of Management in Cambridge.
And the greatest gains came for papers in new areas of research and for papers published in lower-profile journals. Younger researchers who had lower profiles prior to receiving the HHMI award were more likely to see a change as well.
“The effect was much more pronounced when there was more reason to be uncertain about the quality of the science or the scientist before the prize,” Dr Azoulay noted.
This paper, titled “Matthew: Effect or Fable?,” was published in Management Science.
The “Matthew Effect” is a term coined by sociologist Robert K. Merton to describe the possibility that the work of those with high status receives greater attention than equivalent work by those who are not as well known.
Positively identifying this phenomenon in scientific paper citations is difficult, however, because it is hard to separate the status of the author from the quality of the paper. It is possible, after all, that better-known researchers are simply producing higher-quality papers, which get more attention as a result.
But Dr Azoulay and his colleagues said they’ve found a way to address this issue. They looked at papers first published before the authors became HHMI investigators, then examined the citation rates for those papers after the HHMI appointments occurred, compared to a baseline of similar papers whose authors did not receive HHMI appointments.
More specifically, each paper in the study was paired with what Dr Azoulay called a “fraternal twin,” that is, another paper published in the same journal, at the same time, with the same initial citation pattern. For good measure, the authors of the papers in this comparison group were all scientists who had received other early career awards.
In all, from 1984 through 2003, 443 scientists were named HHMI investigators. Dr Azoulay and his colleagues examined 3636 papers written by 424 of those scientists, comparing them to 3636 papers in the control group.
“You couldn’t tell [the 2 sets of papers] apart in terms of citation trajectories, up until the time of the prize,” Dr Azoulay said.
Beyond the overall 12% increase in citations, the effect was nearly twice as great for papers published in lower-profile journals.
Alternately, Dr Azoulay pointed out, “If your paper was published in Cell or Nature or Science, the HHMI [award] doesn’t add a lot.”
Credit: Rhoda Baer
New research indicates that author status affects how frequently scientific papers are cited, but the size of that effect depends on a number of other factors.
Investigators found that, overall, citations increased 12% above the expected level when authors were awarded “prestigious investigator status” at the Howard Hughes Medical Institute (HHMI).
However, certain kinds of research papers benefitted more than others by this increased prestige.
“We find much more of an effect on recent papers published in a short window before the prize,” said study author Pierre Azoulay, PhD, of the MIT Sloan School of Management in Cambridge.
And the greatest gains came for papers in new areas of research and for papers published in lower-profile journals. Younger researchers who had lower profiles prior to receiving the HHMI award were more likely to see a change as well.
“The effect was much more pronounced when there was more reason to be uncertain about the quality of the science or the scientist before the prize,” Dr Azoulay noted.
This paper, titled “Matthew: Effect or Fable?,” was published in Management Science.
The “Matthew Effect” is a term coined by sociologist Robert K. Merton to describe the possibility that the work of those with high status receives greater attention than equivalent work by those who are not as well known.
Positively identifying this phenomenon in scientific paper citations is difficult, however, because it is hard to separate the status of the author from the quality of the paper. It is possible, after all, that better-known researchers are simply producing higher-quality papers, which get more attention as a result.
But Dr Azoulay and his colleagues said they’ve found a way to address this issue. They looked at papers first published before the authors became HHMI investigators, then examined the citation rates for those papers after the HHMI appointments occurred, compared to a baseline of similar papers whose authors did not receive HHMI appointments.
More specifically, each paper in the study was paired with what Dr Azoulay called a “fraternal twin,” that is, another paper published in the same journal, at the same time, with the same initial citation pattern. For good measure, the authors of the papers in this comparison group were all scientists who had received other early career awards.
In all, from 1984 through 2003, 443 scientists were named HHMI investigators. Dr Azoulay and his colleagues examined 3636 papers written by 424 of those scientists, comparing them to 3636 papers in the control group.
“You couldn’t tell [the 2 sets of papers] apart in terms of citation trajectories, up until the time of the prize,” Dr Azoulay said.
Beyond the overall 12% increase in citations, the effect was nearly twice as great for papers published in lower-profile journals.
Alternately, Dr Azoulay pointed out, “If your paper was published in Cell or Nature or Science, the HHMI [award] doesn’t add a lot.”
Group ‘rewrites rules’ on pluripotency
Credit: Haruko Obokata
Researchers say they have developed a novel technique for inducing pluripotency in somatic cells.
Unlike methods for creating induced pluripotent stem cells (iPSCs), the new process—called stimulus-triggered acquisition of pluripotency (STAP)—does not require the introduction of genetic material.
Instead, adult cells must only be injured in order to revert to a pluripotent state.
The investigators tested STAP in preclinical models and reported the results in both a letter and an article published in Nature.
Inspired by plants
Haruko Obokata, PhD, of the RIKEN Center for Developmental Biology in Japan, and her colleagues said this research was inspired by the ability of a plant callus—a node of plant cells created by injuring an existing plant—to grow into a new plant.
The researchers thought this phenomenon suggested that any somatic cell could be de-differentiated through injury.
To find out, they tested cells derived from mice. The team chose hematopoietic cells positive for CD45 because these are lineage-committed, somatic cells that do not express pluripotency-related markers unless they are reprogrammed.
The investigators stressed the cells almost to the point of death by exposing them to various stimuli in vitro, including trauma, a low-oxygen environment, and a low-pH environment.
Within a few days, the cells had recovered from the stressful stimuli by naturally reverting to a pluripotent state. These stem cells were then able to re-differentiate and mature into any type of cell and grow into any type of tissue, depending on the environment into which they were placed.
“It was really surprising to see that such a remarkable transformation could be triggered simply by stimuli from outside of the cell,” Dr Obokata said.
She and her colleagues found that the low-pH environment was most effective for inducing pluripotency.
“Once again, Japanese scientists have unexpectedly rewritten the rules on making pluripotent cells from adult cells,” said Chris Mason, MD, PhD, of the University College London in the UK, who was not involved in this research.
“In 2006, [Shinya] Yamanaka used 4 genes [to create iPSCs]. And now, the far simpler and quicker route discovered by Obokata . . . requires only transient exposure of adult cells to an acidic solution.”
Growth in mice
To examine the cells’ growth potential in vivo, Dr Obokata and her colleagues used CD45+ cells from GFP+ mice. The team exposed the cells to a low-pH environment and found that, in the days following the stress, the cells reverted back to a pluripotent state.
These stem cells then began growing in spherical clusters, similar to a plant callus. The researchers introduced the cell clusters into the developing embryo of a non-GFP mouse and found the clusters could create GFP+ tissues in all organs tested, thereby confirming that the cells are pluripotent.
The investigators think these findings raise the possibility that unknown cellular functions activated through external stress may set somatic cells free from their current commitment and permit them to revert to their naïve state.
“Our findings suggest that, somehow, through part of a natural repair process, mature cells turn off some of the epigenetic controls that inhibit expression of certain nuclear genes that result in differentiation,” said study author Charles Vacanti, MD, of Brigham and Women’s Hospital in Boston.
If this process can be replicated in human cells, researchers might one day be able to use a skin biopsy or blood sample to create stem cells specific to each individual. And this could have implications for treating cancers and other diseases.
The investigators are now testing the STAP technique in human cells.
Credit: Haruko Obokata
Researchers say they have developed a novel technique for inducing pluripotency in somatic cells.
Unlike methods for creating induced pluripotent stem cells (iPSCs), the new process—called stimulus-triggered acquisition of pluripotency (STAP)—does not require the introduction of genetic material.
Instead, adult cells must only be injured in order to revert to a pluripotent state.
The investigators tested STAP in preclinical models and reported the results in both a letter and an article published in Nature.
Inspired by plants
Haruko Obokata, PhD, of the RIKEN Center for Developmental Biology in Japan, and her colleagues said this research was inspired by the ability of a plant callus—a node of plant cells created by injuring an existing plant—to grow into a new plant.
The researchers thought this phenomenon suggested that any somatic cell could be de-differentiated through injury.
To find out, they tested cells derived from mice. The team chose hematopoietic cells positive for CD45 because these are lineage-committed, somatic cells that do not express pluripotency-related markers unless they are reprogrammed.
The investigators stressed the cells almost to the point of death by exposing them to various stimuli in vitro, including trauma, a low-oxygen environment, and a low-pH environment.
Within a few days, the cells had recovered from the stressful stimuli by naturally reverting to a pluripotent state. These stem cells were then able to re-differentiate and mature into any type of cell and grow into any type of tissue, depending on the environment into which they were placed.
“It was really surprising to see that such a remarkable transformation could be triggered simply by stimuli from outside of the cell,” Dr Obokata said.
She and her colleagues found that the low-pH environment was most effective for inducing pluripotency.
“Once again, Japanese scientists have unexpectedly rewritten the rules on making pluripotent cells from adult cells,” said Chris Mason, MD, PhD, of the University College London in the UK, who was not involved in this research.
“In 2006, [Shinya] Yamanaka used 4 genes [to create iPSCs]. And now, the far simpler and quicker route discovered by Obokata . . . requires only transient exposure of adult cells to an acidic solution.”
Growth in mice
To examine the cells’ growth potential in vivo, Dr Obokata and her colleagues used CD45+ cells from GFP+ mice. The team exposed the cells to a low-pH environment and found that, in the days following the stress, the cells reverted back to a pluripotent state.
These stem cells then began growing in spherical clusters, similar to a plant callus. The researchers introduced the cell clusters into the developing embryo of a non-GFP mouse and found the clusters could create GFP+ tissues in all organs tested, thereby confirming that the cells are pluripotent.
The investigators think these findings raise the possibility that unknown cellular functions activated through external stress may set somatic cells free from their current commitment and permit them to revert to their naïve state.
“Our findings suggest that, somehow, through part of a natural repair process, mature cells turn off some of the epigenetic controls that inhibit expression of certain nuclear genes that result in differentiation,” said study author Charles Vacanti, MD, of Brigham and Women’s Hospital in Boston.
If this process can be replicated in human cells, researchers might one day be able to use a skin biopsy or blood sample to create stem cells specific to each individual. And this could have implications for treating cancers and other diseases.
The investigators are now testing the STAP technique in human cells.
Credit: Haruko Obokata
Researchers say they have developed a novel technique for inducing pluripotency in somatic cells.
Unlike methods for creating induced pluripotent stem cells (iPSCs), the new process—called stimulus-triggered acquisition of pluripotency (STAP)—does not require the introduction of genetic material.
Instead, adult cells must only be injured in order to revert to a pluripotent state.
The investigators tested STAP in preclinical models and reported the results in both a letter and an article published in Nature.
Inspired by plants
Haruko Obokata, PhD, of the RIKEN Center for Developmental Biology in Japan, and her colleagues said this research was inspired by the ability of a plant callus—a node of plant cells created by injuring an existing plant—to grow into a new plant.
The researchers thought this phenomenon suggested that any somatic cell could be de-differentiated through injury.
To find out, they tested cells derived from mice. The team chose hematopoietic cells positive for CD45 because these are lineage-committed, somatic cells that do not express pluripotency-related markers unless they are reprogrammed.
The investigators stressed the cells almost to the point of death by exposing them to various stimuli in vitro, including trauma, a low-oxygen environment, and a low-pH environment.
Within a few days, the cells had recovered from the stressful stimuli by naturally reverting to a pluripotent state. These stem cells were then able to re-differentiate and mature into any type of cell and grow into any type of tissue, depending on the environment into which they were placed.
“It was really surprising to see that such a remarkable transformation could be triggered simply by stimuli from outside of the cell,” Dr Obokata said.
She and her colleagues found that the low-pH environment was most effective for inducing pluripotency.
“Once again, Japanese scientists have unexpectedly rewritten the rules on making pluripotent cells from adult cells,” said Chris Mason, MD, PhD, of the University College London in the UK, who was not involved in this research.
“In 2006, [Shinya] Yamanaka used 4 genes [to create iPSCs]. And now, the far simpler and quicker route discovered by Obokata . . . requires only transient exposure of adult cells to an acidic solution.”
Growth in mice
To examine the cells’ growth potential in vivo, Dr Obokata and her colleagues used CD45+ cells from GFP+ mice. The team exposed the cells to a low-pH environment and found that, in the days following the stress, the cells reverted back to a pluripotent state.
These stem cells then began growing in spherical clusters, similar to a plant callus. The researchers introduced the cell clusters into the developing embryo of a non-GFP mouse and found the clusters could create GFP+ tissues in all organs tested, thereby confirming that the cells are pluripotent.
The investigators think these findings raise the possibility that unknown cellular functions activated through external stress may set somatic cells free from their current commitment and permit them to revert to their naïve state.
“Our findings suggest that, somehow, through part of a natural repair process, mature cells turn off some of the epigenetic controls that inhibit expression of certain nuclear genes that result in differentiation,” said study author Charles Vacanti, MD, of Brigham and Women’s Hospital in Boston.
If this process can be replicated in human cells, researchers might one day be able to use a skin biopsy or blood sample to create stem cells specific to each individual. And this could have implications for treating cancers and other diseases.
The investigators are now testing the STAP technique in human cells.
Compliance with HAI policies varies across US
Credit: Rhoda Baer
An analysis of US intensive care units (ICUs) shows uneven compliance with policies for preventing healthcare-associated infections (HAIs).
The survey of more than 1500 ICUs showed that a majority of hospitals had prevention policies in place for central line-associated bloodstream infections (CLABSIs). But adherence to these policies ranged from 37% to 71%.
And both the prevalence of and adherence to policies was even lower for 2 other common HAIs.
Patricia W. Stone PhD, of the Columbia University School of Nursing in New York, and her colleagues shared these results in the American Journal of Infection Control.
The researchers surveyed 1534 ICUs at 975 hospitals. They assessed the implementation of 16 prescribed infection-prevention measures, as well as clinician adherence to these policies for the prevention of CLABSIs, ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infections (CAUTIs).
The survey revealed that most hospitals had policies in place to prevent CLABSIs. Prevalence ranged from 87% for checking lines daily to 97% for applying chlorhexidine at catheter insertion sites.
This was followed by VAP prevention policies, which ranged from 69% for providing chlorhexidine mouth care to 91% for raising the head of the bed.
And finally, the presence of CAUTI policies ranged from 27% for nurse-initiated urinary catheterization to 68% for portable bladder ultrasounds. The researchers said it was surprising that evidence-based practices related to CAUTI prevention have not been well implemented, as CAUTIs are the most frequent HAI.
The survey also showed that many of the ICUs fell short in adhering to infection-prevention policies. Adherence ranged from 37% to 71% for CLABSIs, 45% to 55% for VAP, and 6% to 27% for CAUTIs.
The researchers analyzed other characteristics of the hospitals and their infection-prevention programs as well. The hospitals had an average of 52,578 annual patient-days, with 11,377 admissions, 32 ICU beds, 12 specialty beds, and 182 other beds.
Roughly a third of the departments (34%) had an electronic surveillance system, and most were commercially developed (86%).
Eighty-four percent of the institutions used hospitalists, 49% used intensivists, and 50% had a physician hospital epidemiologist. The average number of infection preventionists per 100 beds was 1.2, but certification of these staff members varied.
Having gained new insight into infection-prevention policies at hospitals across the US, the researchers are now planning to analyze the associations between HAI rates and characteristics of infection-prevention programs. They also plan to look at the relationship between HAI rates and adherence to evidence-based policies.
Credit: Rhoda Baer
An analysis of US intensive care units (ICUs) shows uneven compliance with policies for preventing healthcare-associated infections (HAIs).
The survey of more than 1500 ICUs showed that a majority of hospitals had prevention policies in place for central line-associated bloodstream infections (CLABSIs). But adherence to these policies ranged from 37% to 71%.
And both the prevalence of and adherence to policies was even lower for 2 other common HAIs.
Patricia W. Stone PhD, of the Columbia University School of Nursing in New York, and her colleagues shared these results in the American Journal of Infection Control.
The researchers surveyed 1534 ICUs at 975 hospitals. They assessed the implementation of 16 prescribed infection-prevention measures, as well as clinician adherence to these policies for the prevention of CLABSIs, ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infections (CAUTIs).
The survey revealed that most hospitals had policies in place to prevent CLABSIs. Prevalence ranged from 87% for checking lines daily to 97% for applying chlorhexidine at catheter insertion sites.
This was followed by VAP prevention policies, which ranged from 69% for providing chlorhexidine mouth care to 91% for raising the head of the bed.
And finally, the presence of CAUTI policies ranged from 27% for nurse-initiated urinary catheterization to 68% for portable bladder ultrasounds. The researchers said it was surprising that evidence-based practices related to CAUTI prevention have not been well implemented, as CAUTIs are the most frequent HAI.
The survey also showed that many of the ICUs fell short in adhering to infection-prevention policies. Adherence ranged from 37% to 71% for CLABSIs, 45% to 55% for VAP, and 6% to 27% for CAUTIs.
The researchers analyzed other characteristics of the hospitals and their infection-prevention programs as well. The hospitals had an average of 52,578 annual patient-days, with 11,377 admissions, 32 ICU beds, 12 specialty beds, and 182 other beds.
Roughly a third of the departments (34%) had an electronic surveillance system, and most were commercially developed (86%).
Eighty-four percent of the institutions used hospitalists, 49% used intensivists, and 50% had a physician hospital epidemiologist. The average number of infection preventionists per 100 beds was 1.2, but certification of these staff members varied.
Having gained new insight into infection-prevention policies at hospitals across the US, the researchers are now planning to analyze the associations between HAI rates and characteristics of infection-prevention programs. They also plan to look at the relationship between HAI rates and adherence to evidence-based policies.
Credit: Rhoda Baer
An analysis of US intensive care units (ICUs) shows uneven compliance with policies for preventing healthcare-associated infections (HAIs).
The survey of more than 1500 ICUs showed that a majority of hospitals had prevention policies in place for central line-associated bloodstream infections (CLABSIs). But adherence to these policies ranged from 37% to 71%.
And both the prevalence of and adherence to policies was even lower for 2 other common HAIs.
Patricia W. Stone PhD, of the Columbia University School of Nursing in New York, and her colleagues shared these results in the American Journal of Infection Control.
The researchers surveyed 1534 ICUs at 975 hospitals. They assessed the implementation of 16 prescribed infection-prevention measures, as well as clinician adherence to these policies for the prevention of CLABSIs, ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infections (CAUTIs).
The survey revealed that most hospitals had policies in place to prevent CLABSIs. Prevalence ranged from 87% for checking lines daily to 97% for applying chlorhexidine at catheter insertion sites.
This was followed by VAP prevention policies, which ranged from 69% for providing chlorhexidine mouth care to 91% for raising the head of the bed.
And finally, the presence of CAUTI policies ranged from 27% for nurse-initiated urinary catheterization to 68% for portable bladder ultrasounds. The researchers said it was surprising that evidence-based practices related to CAUTI prevention have not been well implemented, as CAUTIs are the most frequent HAI.
The survey also showed that many of the ICUs fell short in adhering to infection-prevention policies. Adherence ranged from 37% to 71% for CLABSIs, 45% to 55% for VAP, and 6% to 27% for CAUTIs.
The researchers analyzed other characteristics of the hospitals and their infection-prevention programs as well. The hospitals had an average of 52,578 annual patient-days, with 11,377 admissions, 32 ICU beds, 12 specialty beds, and 182 other beds.
Roughly a third of the departments (34%) had an electronic surveillance system, and most were commercially developed (86%).
Eighty-four percent of the institutions used hospitalists, 49% used intensivists, and 50% had a physician hospital epidemiologist. The average number of infection preventionists per 100 beds was 1.2, but certification of these staff members varied.
Having gained new insight into infection-prevention policies at hospitals across the US, the researchers are now planning to analyze the associations between HAI rates and characteristics of infection-prevention programs. They also plan to look at the relationship between HAI rates and adherence to evidence-based policies.
System allows precise gene editing in monkeys
Credit: Yuyu Niu et al.
Although monkeys can be useful as models of human disease, precisely modifying their genes has proven difficult.
Now, investigators say they’ve achieved precise gene modification in monkeys using the CRISPR/Cas9 system.
“Our study shows that the CRISPR/Cas9 system enables simultaneous disruption of 2 target genes in 1 step, without producing off-target mutations,” said Jiahao Sha, PhD, of Nanjing Medical University in Nanjing, China.
“Considering that many human diseases are caused by genetic abnormalities, targeted genetic modification in monkeys is invaluable for the generation of human disease models.”
Dr Sha and his colleagues described this research in Cell.
The CRISPR/Cas9 system is a gene-editing tool capable of targeting specific DNA sequences in the genome. Cas9 proteins, which are directed by single-guide RNAs to specific sites in the genome, generate mutations by introducing double-stranded DNA breaks.
Until now, the CRISPR/Cas9 system and other targeted gene-editing techniques were successfully applied to mammals such as mice and rats, but not to primates.
Dr Sha and his colleagues injected messenger RNA encoding Cas9, as well as single-guide RNAs designed to target 3 specific genes, into one-cell-stage embryos of cynomolgus monkeys.
After sequencing DNA from 15 embryos, the team found that 8 of these embryos showed evidence of simultaneous mutations in 2 of the target genes.
The researchers then transferred genetically modified embryos into surrogate females, one of which gave birth to a set of twins. By sequencing the twins’ DNA, the team found mutations in 2 of the target genes.
Moreover, the CRISPR/Cas9 system did not produce mutations at genomic sites that were not targeted. And this suggests the tool will not cause undesirable effects when applied to monkeys.
“With the precise genomic targeting of the CRISPR/Cas9 system, we expect that many disease models will be generated in monkeys,” said Weizhi Ji, PhD, of the Yunnan Key Laboratory of Primate Biomedical Research in Kunming, China.
“[This] will significantly advance the development of therapeutic strategies in biomedical research.”
Credit: Yuyu Niu et al.
Although monkeys can be useful as models of human disease, precisely modifying their genes has proven difficult.
Now, investigators say they’ve achieved precise gene modification in monkeys using the CRISPR/Cas9 system.
“Our study shows that the CRISPR/Cas9 system enables simultaneous disruption of 2 target genes in 1 step, without producing off-target mutations,” said Jiahao Sha, PhD, of Nanjing Medical University in Nanjing, China.
“Considering that many human diseases are caused by genetic abnormalities, targeted genetic modification in monkeys is invaluable for the generation of human disease models.”
Dr Sha and his colleagues described this research in Cell.
The CRISPR/Cas9 system is a gene-editing tool capable of targeting specific DNA sequences in the genome. Cas9 proteins, which are directed by single-guide RNAs to specific sites in the genome, generate mutations by introducing double-stranded DNA breaks.
Until now, the CRISPR/Cas9 system and other targeted gene-editing techniques were successfully applied to mammals such as mice and rats, but not to primates.
Dr Sha and his colleagues injected messenger RNA encoding Cas9, as well as single-guide RNAs designed to target 3 specific genes, into one-cell-stage embryos of cynomolgus monkeys.
After sequencing DNA from 15 embryos, the team found that 8 of these embryos showed evidence of simultaneous mutations in 2 of the target genes.
The researchers then transferred genetically modified embryos into surrogate females, one of which gave birth to a set of twins. By sequencing the twins’ DNA, the team found mutations in 2 of the target genes.
Moreover, the CRISPR/Cas9 system did not produce mutations at genomic sites that were not targeted. And this suggests the tool will not cause undesirable effects when applied to monkeys.
“With the precise genomic targeting of the CRISPR/Cas9 system, we expect that many disease models will be generated in monkeys,” said Weizhi Ji, PhD, of the Yunnan Key Laboratory of Primate Biomedical Research in Kunming, China.
“[This] will significantly advance the development of therapeutic strategies in biomedical research.”
Credit: Yuyu Niu et al.
Although monkeys can be useful as models of human disease, precisely modifying their genes has proven difficult.
Now, investigators say they’ve achieved precise gene modification in monkeys using the CRISPR/Cas9 system.
“Our study shows that the CRISPR/Cas9 system enables simultaneous disruption of 2 target genes in 1 step, without producing off-target mutations,” said Jiahao Sha, PhD, of Nanjing Medical University in Nanjing, China.
“Considering that many human diseases are caused by genetic abnormalities, targeted genetic modification in monkeys is invaluable for the generation of human disease models.”
Dr Sha and his colleagues described this research in Cell.
The CRISPR/Cas9 system is a gene-editing tool capable of targeting specific DNA sequences in the genome. Cas9 proteins, which are directed by single-guide RNAs to specific sites in the genome, generate mutations by introducing double-stranded DNA breaks.
Until now, the CRISPR/Cas9 system and other targeted gene-editing techniques were successfully applied to mammals such as mice and rats, but not to primates.
Dr Sha and his colleagues injected messenger RNA encoding Cas9, as well as single-guide RNAs designed to target 3 specific genes, into one-cell-stage embryos of cynomolgus monkeys.
After sequencing DNA from 15 embryos, the team found that 8 of these embryos showed evidence of simultaneous mutations in 2 of the target genes.
The researchers then transferred genetically modified embryos into surrogate females, one of which gave birth to a set of twins. By sequencing the twins’ DNA, the team found mutations in 2 of the target genes.
Moreover, the CRISPR/Cas9 system did not produce mutations at genomic sites that were not targeted. And this suggests the tool will not cause undesirable effects when applied to monkeys.
“With the precise genomic targeting of the CRISPR/Cas9 system, we expect that many disease models will be generated in monkeys,” said Weizhi Ji, PhD, of the Yunnan Key Laboratory of Primate Biomedical Research in Kunming, China.
“[This] will significantly advance the development of therapeutic strategies in biomedical research.”
Malaria screening program unsuccessful
blood cell; Credit: St Jude
Children’s Research Hospital
A school-based, intermittent screening and treatment program for malaria did not confer any benefits for children living in an area of low-to-moderate malaria transmission.
The program, which was implemented at schools in Kenya, did not significantly reduce the incidence of malaria infection or the prevalence of anemia.
Katherine Halliday, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues reported these results in PLOS Medicine.
The study included 5233 children, ages 5 to 20, studying at 101 government schools located on the south coast of Kenya. Fifty-one of the schools were randomized to the intermittent screening and treatment program.
Over 24 months, children in these schools underwent screening for malaria parasites once each term (a total of 5 times). And those who tested positive for malaria parasitemia (whether symptomatic or asymptomatic) received 6 cycles of treatment with the anti-malarial drug artemether-lumefantrine.
Eighty-four percent of the children were screened at 4 or more rounds, and 66.8% were screened at all 5 rounds. By the fifth round, 20% of children had been lost due to death, withdrawal, or migration.
The percentage of children who were positive for malaria at each screening ranged from 14.8% to 19.2%, and there was no distinct trend over time. Overall, 99.1% of the positive results led to treatment, and 92.6% of these were recorded as receiving the fully supervised, 6-dose treatment regimen.
The investigators followed a majority of the children in each group for an additional 24 months after the intervention ended. And the team found that the intervention had no significant impact on the prevalence of Plasmodium falciparum infection at 12 months or 24 months.
At 12 months, the prevalence of P falciparum (adjusted for age, sex, and stratification effects) was 10.7% in the intervention group and 14.3% in the control group (P=0.131). At 24 months, the prevalence of P falciparum was 11.8% in the intervention group and 8.5% in the control group (P=0.124).
Similarly, there was no significant difference between the 2 groups with regard to anemia.
At 12 months, the prevalence of anemia was 38.5% among controls and 40.1% in the intervention group (P=0.621). At 24 months, the prevalence was 39.5% among controls and 41.5% in the intervention group (P=0.953).
The investigators also evaluated education-related outcomes at 9 months and 24 months of follow-up. They found no significant difference between the study groups with regard to classroom attention.
However, younger children in the intervention group did not score as well as controls in spelling or arithmetic tests.
The team said this may be a chance finding, or it may indicate that apprehension about the finger prick needed for the diagnostic test had a negative effect on the children’s performance during educational tests.
In closing, the investigators said there are a number of possible reasons why this screening and treatment intervention proved unsuccesful.
These include geographical heterogeneity in transmission, a rapid rate of reinfection following treatment, the variable reliability of the diagnostic tests used, and the relative contribution of malaria to the etiology of anemia in this setting.
In a related perspective article, Lorenz von Seidlein, MD, PhD, of the Menzies School of Health Research in Casuarina, Australia, discusses these possibilities in more detail, as well as the wider issues involved in failure of screening and treating as a malaria elimination strategy.
blood cell; Credit: St Jude
Children’s Research Hospital
A school-based, intermittent screening and treatment program for malaria did not confer any benefits for children living in an area of low-to-moderate malaria transmission.
The program, which was implemented at schools in Kenya, did not significantly reduce the incidence of malaria infection or the prevalence of anemia.
Katherine Halliday, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues reported these results in PLOS Medicine.
The study included 5233 children, ages 5 to 20, studying at 101 government schools located on the south coast of Kenya. Fifty-one of the schools were randomized to the intermittent screening and treatment program.
Over 24 months, children in these schools underwent screening for malaria parasites once each term (a total of 5 times). And those who tested positive for malaria parasitemia (whether symptomatic or asymptomatic) received 6 cycles of treatment with the anti-malarial drug artemether-lumefantrine.
Eighty-four percent of the children were screened at 4 or more rounds, and 66.8% were screened at all 5 rounds. By the fifth round, 20% of children had been lost due to death, withdrawal, or migration.
The percentage of children who were positive for malaria at each screening ranged from 14.8% to 19.2%, and there was no distinct trend over time. Overall, 99.1% of the positive results led to treatment, and 92.6% of these were recorded as receiving the fully supervised, 6-dose treatment regimen.
The investigators followed a majority of the children in each group for an additional 24 months after the intervention ended. And the team found that the intervention had no significant impact on the prevalence of Plasmodium falciparum infection at 12 months or 24 months.
At 12 months, the prevalence of P falciparum (adjusted for age, sex, and stratification effects) was 10.7% in the intervention group and 14.3% in the control group (P=0.131). At 24 months, the prevalence of P falciparum was 11.8% in the intervention group and 8.5% in the control group (P=0.124).
Similarly, there was no significant difference between the 2 groups with regard to anemia.
At 12 months, the prevalence of anemia was 38.5% among controls and 40.1% in the intervention group (P=0.621). At 24 months, the prevalence was 39.5% among controls and 41.5% in the intervention group (P=0.953).
The investigators also evaluated education-related outcomes at 9 months and 24 months of follow-up. They found no significant difference between the study groups with regard to classroom attention.
However, younger children in the intervention group did not score as well as controls in spelling or arithmetic tests.
The team said this may be a chance finding, or it may indicate that apprehension about the finger prick needed for the diagnostic test had a negative effect on the children’s performance during educational tests.
In closing, the investigators said there are a number of possible reasons why this screening and treatment intervention proved unsuccesful.
These include geographical heterogeneity in transmission, a rapid rate of reinfection following treatment, the variable reliability of the diagnostic tests used, and the relative contribution of malaria to the etiology of anemia in this setting.
In a related perspective article, Lorenz von Seidlein, MD, PhD, of the Menzies School of Health Research in Casuarina, Australia, discusses these possibilities in more detail, as well as the wider issues involved in failure of screening and treating as a malaria elimination strategy.
blood cell; Credit: St Jude
Children’s Research Hospital
A school-based, intermittent screening and treatment program for malaria did not confer any benefits for children living in an area of low-to-moderate malaria transmission.
The program, which was implemented at schools in Kenya, did not significantly reduce the incidence of malaria infection or the prevalence of anemia.
Katherine Halliday, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues reported these results in PLOS Medicine.
The study included 5233 children, ages 5 to 20, studying at 101 government schools located on the south coast of Kenya. Fifty-one of the schools were randomized to the intermittent screening and treatment program.
Over 24 months, children in these schools underwent screening for malaria parasites once each term (a total of 5 times). And those who tested positive for malaria parasitemia (whether symptomatic or asymptomatic) received 6 cycles of treatment with the anti-malarial drug artemether-lumefantrine.
Eighty-four percent of the children were screened at 4 or more rounds, and 66.8% were screened at all 5 rounds. By the fifth round, 20% of children had been lost due to death, withdrawal, or migration.
The percentage of children who were positive for malaria at each screening ranged from 14.8% to 19.2%, and there was no distinct trend over time. Overall, 99.1% of the positive results led to treatment, and 92.6% of these were recorded as receiving the fully supervised, 6-dose treatment regimen.
The investigators followed a majority of the children in each group for an additional 24 months after the intervention ended. And the team found that the intervention had no significant impact on the prevalence of Plasmodium falciparum infection at 12 months or 24 months.
At 12 months, the prevalence of P falciparum (adjusted for age, sex, and stratification effects) was 10.7% in the intervention group and 14.3% in the control group (P=0.131). At 24 months, the prevalence of P falciparum was 11.8% in the intervention group and 8.5% in the control group (P=0.124).
Similarly, there was no significant difference between the 2 groups with regard to anemia.
At 12 months, the prevalence of anemia was 38.5% among controls and 40.1% in the intervention group (P=0.621). At 24 months, the prevalence was 39.5% among controls and 41.5% in the intervention group (P=0.953).
The investigators also evaluated education-related outcomes at 9 months and 24 months of follow-up. They found no significant difference between the study groups with regard to classroom attention.
However, younger children in the intervention group did not score as well as controls in spelling or arithmetic tests.
The team said this may be a chance finding, or it may indicate that apprehension about the finger prick needed for the diagnostic test had a negative effect on the children’s performance during educational tests.
In closing, the investigators said there are a number of possible reasons why this screening and treatment intervention proved unsuccesful.
These include geographical heterogeneity in transmission, a rapid rate of reinfection following treatment, the variable reliability of the diagnostic tests used, and the relative contribution of malaria to the etiology of anemia in this setting.
In a related perspective article, Lorenz von Seidlein, MD, PhD, of the Menzies School of Health Research in Casuarina, Australia, discusses these possibilities in more detail, as well as the wider issues involved in failure of screening and treating as a malaria elimination strategy.
Analysis reveals effects of sponsorship on animal studies
A new analysis indicates that animal studies not funded by industry produce favorable results more often than animal studies that are industry-funded.
In other words, published reports of non-industry-sponsored studies were more likely to contain data suggesting a drug was effective.
However, reports of industry-funded studies were more likely to contain favorable conclusions, even though data were less favorable.
Investigators recounted these findings in PLOS Biology.
They analyzed 63 studies in which statins were tested in animal models. Forty-two of the studies had quantitative results and disclosed sponsorship.
Among these studies, industry-sponsored research was less likely to measure a benefit for the statins in slowing or preventing arterial disease. Favorable results were reported in 47% (9/19) of the industry-sponsored studies and 72% (18/25) of the studies not sponsored by industry.
“The interests of the pharmaceutical industry might be best served by underestimating efficacy prior to clinical trials and overestimating efficacy in clinical trials,” said study author Lisa Bero, PhD, of the University of California, San Francisco.
“By underestimating efficacy in preclinical studies, the pharmaceutical industry could reduce the money spent on clinical trials that did not lead to marketable products. Because demonstrating drug efficacy in human studies is linked to drug company profits, drug companies may have more incentive to publish favorable efficacy findings of human drug studies than animal studies.”
However, Dr Bero and her colleagues also found that favorable conclusions were more likely in industry-sponsored studies, even when data were less favorable. Study authors drew favorable conclusions in 94.7% (18/19) of industry-sponsored studies and 75% (21/28) of studies not funded by industry.
Other key findings of this analysis were that methodological problems were common in both types of studies, and harmful side effects were not investigated.
“Not a single animal study we looked at assessed adverse events following the statin intervention,” Dr Bero said. “As toxicity data from animal studies must be submitted to drug regulatory authorities before a compound can proceed to testing in humans, it is surprising that so little data on harm appear in the published scientific literature.”
The investigators also noted that about half of the studies analyzed were randomized, and about half were blinded. Inclusion and exclusion criteria were often not included in the published reports, and many studies failed to account properly for changes in the assigned treatment arm that occurred during the course of treatment.
Most of the studies in this analysis were conducted in rabbits and mice. To gauge atherosclerosis, targeted by statins, investigators quantified qualities such as the number of damaged blood vessels, blood-vessel diameter, plaque severity, blockage to coronary and other arteries, and plaque rupture.
A new analysis indicates that animal studies not funded by industry produce favorable results more often than animal studies that are industry-funded.
In other words, published reports of non-industry-sponsored studies were more likely to contain data suggesting a drug was effective.
However, reports of industry-funded studies were more likely to contain favorable conclusions, even though data were less favorable.
Investigators recounted these findings in PLOS Biology.
They analyzed 63 studies in which statins were tested in animal models. Forty-two of the studies had quantitative results and disclosed sponsorship.
Among these studies, industry-sponsored research was less likely to measure a benefit for the statins in slowing or preventing arterial disease. Favorable results were reported in 47% (9/19) of the industry-sponsored studies and 72% (18/25) of the studies not sponsored by industry.
“The interests of the pharmaceutical industry might be best served by underestimating efficacy prior to clinical trials and overestimating efficacy in clinical trials,” said study author Lisa Bero, PhD, of the University of California, San Francisco.
“By underestimating efficacy in preclinical studies, the pharmaceutical industry could reduce the money spent on clinical trials that did not lead to marketable products. Because demonstrating drug efficacy in human studies is linked to drug company profits, drug companies may have more incentive to publish favorable efficacy findings of human drug studies than animal studies.”
However, Dr Bero and her colleagues also found that favorable conclusions were more likely in industry-sponsored studies, even when data were less favorable. Study authors drew favorable conclusions in 94.7% (18/19) of industry-sponsored studies and 75% (21/28) of studies not funded by industry.
Other key findings of this analysis were that methodological problems were common in both types of studies, and harmful side effects were not investigated.
“Not a single animal study we looked at assessed adverse events following the statin intervention,” Dr Bero said. “As toxicity data from animal studies must be submitted to drug regulatory authorities before a compound can proceed to testing in humans, it is surprising that so little data on harm appear in the published scientific literature.”
The investigators also noted that about half of the studies analyzed were randomized, and about half were blinded. Inclusion and exclusion criteria were often not included in the published reports, and many studies failed to account properly for changes in the assigned treatment arm that occurred during the course of treatment.
Most of the studies in this analysis were conducted in rabbits and mice. To gauge atherosclerosis, targeted by statins, investigators quantified qualities such as the number of damaged blood vessels, blood-vessel diameter, plaque severity, blockage to coronary and other arteries, and plaque rupture.
A new analysis indicates that animal studies not funded by industry produce favorable results more often than animal studies that are industry-funded.
In other words, published reports of non-industry-sponsored studies were more likely to contain data suggesting a drug was effective.
However, reports of industry-funded studies were more likely to contain favorable conclusions, even though data were less favorable.
Investigators recounted these findings in PLOS Biology.
They analyzed 63 studies in which statins were tested in animal models. Forty-two of the studies had quantitative results and disclosed sponsorship.
Among these studies, industry-sponsored research was less likely to measure a benefit for the statins in slowing or preventing arterial disease. Favorable results were reported in 47% (9/19) of the industry-sponsored studies and 72% (18/25) of the studies not sponsored by industry.
“The interests of the pharmaceutical industry might be best served by underestimating efficacy prior to clinical trials and overestimating efficacy in clinical trials,” said study author Lisa Bero, PhD, of the University of California, San Francisco.
“By underestimating efficacy in preclinical studies, the pharmaceutical industry could reduce the money spent on clinical trials that did not lead to marketable products. Because demonstrating drug efficacy in human studies is linked to drug company profits, drug companies may have more incentive to publish favorable efficacy findings of human drug studies than animal studies.”
However, Dr Bero and her colleagues also found that favorable conclusions were more likely in industry-sponsored studies, even when data were less favorable. Study authors drew favorable conclusions in 94.7% (18/19) of industry-sponsored studies and 75% (21/28) of studies not funded by industry.
Other key findings of this analysis were that methodological problems were common in both types of studies, and harmful side effects were not investigated.
“Not a single animal study we looked at assessed adverse events following the statin intervention,” Dr Bero said. “As toxicity data from animal studies must be submitted to drug regulatory authorities before a compound can proceed to testing in humans, it is surprising that so little data on harm appear in the published scientific literature.”
The investigators also noted that about half of the studies analyzed were randomized, and about half were blinded. Inclusion and exclusion criteria were often not included in the published reports, and many studies failed to account properly for changes in the assigned treatment arm that occurred during the course of treatment.
Most of the studies in this analysis were conducted in rabbits and mice. To gauge atherosclerosis, targeted by statins, investigators quantified qualities such as the number of damaged blood vessels, blood-vessel diameter, plaque severity, blockage to coronary and other arteries, and plaque rupture.
Physical activity may cut death risk in male cancer survivors
Credit: Jason E. Miller
Physical activity may reduce the risk of mortality in male cancer survivors, according to research published in the Journal of Physical Activity & Health.
In a study of more than 1000 male cancer survivors, participants who were most active—expending more than 12,600 kilojoules per week in physical activity—cut their risk of death roughly in half.
This was in comparison to the least active cancer survivors—those who burned fewer than 2100 kilojoules per week.
Kathleen Y. Wolin, PhD, of Loyola University Chicago Stritch School of Medicine, and her colleagues conducted this research using data from the Harvard Alumni Health Study, an ongoing study of men who entered Harvard as undergraduates between 1916 and 1950.
The researchers looked at 1021 men, with an average age of 71, who had been diagnosed with cancers.
In 1988, the men completed questionnaires reporting their physical activities, including walking, stair-climbing, and participation in sports and recreational activities. Their physical activities were updated in 1993, and researchers followed the men until 2008.
In all, 777 of the men died—337 from cancer, 190 from cardiovascular disease, 228 from other causes, and 22 from unknown causes.
Compared with men who expended fewer than 2100 kilojoules per week in physical activity, men who expended more than 12,600 kilojoules per week were 48% less likely to die of any cause during the follow-up period. (Expending 12,600 kilojoules can be achieved with about 6 to 8 hours of moderate-intensity physical activity.)
This finding was adjusted for age, smoking habits, body mass index, early parental mortality, and dietary variables.
When the researchers tried to adjust for cancer severity and treatment, they were only able to collect data for 70 men. But the results were not very different from the prior analysis. The most active men were 49% less likely to die of any cause than the least active men.
The team also decided to analyze men who were diagnosed with cancer at least 5 years before baseline (n=421). And among these men, the most active were 52% less likely than the least active to die.
Similarly, among men diagnosed at least 10 years before baseline (n=262), the most active cancer survivors were 63% less likely to die of any cause than the least active survivors.
The researchers also obtained similar results when they assessed mortality from cancer and cardiovascular disease. The most physically active cancer survivors were 38% less likely to die of cancer and 49% less likely to die of cardiovascular disease during follow-up.
Credit: Jason E. Miller
Physical activity may reduce the risk of mortality in male cancer survivors, according to research published in the Journal of Physical Activity & Health.
In a study of more than 1000 male cancer survivors, participants who were most active—expending more than 12,600 kilojoules per week in physical activity—cut their risk of death roughly in half.
This was in comparison to the least active cancer survivors—those who burned fewer than 2100 kilojoules per week.
Kathleen Y. Wolin, PhD, of Loyola University Chicago Stritch School of Medicine, and her colleagues conducted this research using data from the Harvard Alumni Health Study, an ongoing study of men who entered Harvard as undergraduates between 1916 and 1950.
The researchers looked at 1021 men, with an average age of 71, who had been diagnosed with cancers.
In 1988, the men completed questionnaires reporting their physical activities, including walking, stair-climbing, and participation in sports and recreational activities. Their physical activities were updated in 1993, and researchers followed the men until 2008.
In all, 777 of the men died—337 from cancer, 190 from cardiovascular disease, 228 from other causes, and 22 from unknown causes.
Compared with men who expended fewer than 2100 kilojoules per week in physical activity, men who expended more than 12,600 kilojoules per week were 48% less likely to die of any cause during the follow-up period. (Expending 12,600 kilojoules can be achieved with about 6 to 8 hours of moderate-intensity physical activity.)
This finding was adjusted for age, smoking habits, body mass index, early parental mortality, and dietary variables.
When the researchers tried to adjust for cancer severity and treatment, they were only able to collect data for 70 men. But the results were not very different from the prior analysis. The most active men were 49% less likely to die of any cause than the least active men.
The team also decided to analyze men who were diagnosed with cancer at least 5 years before baseline (n=421). And among these men, the most active were 52% less likely than the least active to die.
Similarly, among men diagnosed at least 10 years before baseline (n=262), the most active cancer survivors were 63% less likely to die of any cause than the least active survivors.
The researchers also obtained similar results when they assessed mortality from cancer and cardiovascular disease. The most physically active cancer survivors were 38% less likely to die of cancer and 49% less likely to die of cardiovascular disease during follow-up.
Credit: Jason E. Miller
Physical activity may reduce the risk of mortality in male cancer survivors, according to research published in the Journal of Physical Activity & Health.
In a study of more than 1000 male cancer survivors, participants who were most active—expending more than 12,600 kilojoules per week in physical activity—cut their risk of death roughly in half.
This was in comparison to the least active cancer survivors—those who burned fewer than 2100 kilojoules per week.
Kathleen Y. Wolin, PhD, of Loyola University Chicago Stritch School of Medicine, and her colleagues conducted this research using data from the Harvard Alumni Health Study, an ongoing study of men who entered Harvard as undergraduates between 1916 and 1950.
The researchers looked at 1021 men, with an average age of 71, who had been diagnosed with cancers.
In 1988, the men completed questionnaires reporting their physical activities, including walking, stair-climbing, and participation in sports and recreational activities. Their physical activities were updated in 1993, and researchers followed the men until 2008.
In all, 777 of the men died—337 from cancer, 190 from cardiovascular disease, 228 from other causes, and 22 from unknown causes.
Compared with men who expended fewer than 2100 kilojoules per week in physical activity, men who expended more than 12,600 kilojoules per week were 48% less likely to die of any cause during the follow-up period. (Expending 12,600 kilojoules can be achieved with about 6 to 8 hours of moderate-intensity physical activity.)
This finding was adjusted for age, smoking habits, body mass index, early parental mortality, and dietary variables.
When the researchers tried to adjust for cancer severity and treatment, they were only able to collect data for 70 men. But the results were not very different from the prior analysis. The most active men were 49% less likely to die of any cause than the least active men.
The team also decided to analyze men who were diagnosed with cancer at least 5 years before baseline (n=421). And among these men, the most active were 52% less likely than the least active to die.
Similarly, among men diagnosed at least 10 years before baseline (n=262), the most active cancer survivors were 63% less likely to die of any cause than the least active survivors.
The researchers also obtained similar results when they assessed mortality from cancer and cardiovascular disease. The most physically active cancer survivors were 38% less likely to die of cancer and 49% less likely to die of cardiovascular disease during follow-up.
Estrogen promotes HSC activity
Scientists have long thought that hematopoietic stem cells (HSCs) are regulated similarly in males and females.
But research conducted in mice has shown that HSCs exhibit sex differences in cell-cycle regulation.
The researchers discovered that HSCs in female mice divided significantly more frequently than HSCs in male mice, and this appeared to be driven by estrogen.
Sean Morrison, PhD, of UT Southwestern Medical Center in Dallas, and his colleagues detailed these discoveries in a letter to Nature.
The research suggested that differences in HSC division depend on the ovaries and not the testes. When the investigators administered estradiol, a hormone produced mainly in the ovaries, to male and female mice, HSC division increased in both sexes.
And experiments in pregnant mice highlighted the importance of estrogen in HSC activity. Estrogen levels increased during pregnancy, which increased HSC division, HSC frequency, cellularity, and erythropoiesis in the spleen.
“Elevated estrogen levels that are sustained during pregnancy induce stem cell mobilization and red cell production in the spleen, which serves as a reserve site for additional red blood cell production,” Dr Morrison said.
He and his colleagues also found that HSCs expressed high levels of estrogen receptor-alpha. And deleting the receptor reduced HSC division in female mice but not in males.
In pregnant mice, deleting the receptor attenuated the previously observed increases in HSC division, HSC frequency, and erythropoiesis.
These results suggest estrogen acts directly on HSCs to increase their proliferation and the number of red blood cells they generate.
“If estrogen has the same effect on stem cells in humans as in mice, then this effect raises a number of possibilities that could change the way we treat people with diseases of blood cell formation,” Dr Morrison said.
“Can we promote regeneration in the blood-forming system by administering estrogen? Can we reduce the toxicity of chemotherapy to the blood-forming system by taking into account estrogen levels in female patients? Does estrogen promote the growth of some blood cancers? There are numerous clinical opportunities to pursue.”
Scientists have long thought that hematopoietic stem cells (HSCs) are regulated similarly in males and females.
But research conducted in mice has shown that HSCs exhibit sex differences in cell-cycle regulation.
The researchers discovered that HSCs in female mice divided significantly more frequently than HSCs in male mice, and this appeared to be driven by estrogen.
Sean Morrison, PhD, of UT Southwestern Medical Center in Dallas, and his colleagues detailed these discoveries in a letter to Nature.
The research suggested that differences in HSC division depend on the ovaries and not the testes. When the investigators administered estradiol, a hormone produced mainly in the ovaries, to male and female mice, HSC division increased in both sexes.
And experiments in pregnant mice highlighted the importance of estrogen in HSC activity. Estrogen levels increased during pregnancy, which increased HSC division, HSC frequency, cellularity, and erythropoiesis in the spleen.
“Elevated estrogen levels that are sustained during pregnancy induce stem cell mobilization and red cell production in the spleen, which serves as a reserve site for additional red blood cell production,” Dr Morrison said.
He and his colleagues also found that HSCs expressed high levels of estrogen receptor-alpha. And deleting the receptor reduced HSC division in female mice but not in males.
In pregnant mice, deleting the receptor attenuated the previously observed increases in HSC division, HSC frequency, and erythropoiesis.
These results suggest estrogen acts directly on HSCs to increase their proliferation and the number of red blood cells they generate.
“If estrogen has the same effect on stem cells in humans as in mice, then this effect raises a number of possibilities that could change the way we treat people with diseases of blood cell formation,” Dr Morrison said.
“Can we promote regeneration in the blood-forming system by administering estrogen? Can we reduce the toxicity of chemotherapy to the blood-forming system by taking into account estrogen levels in female patients? Does estrogen promote the growth of some blood cancers? There are numerous clinical opportunities to pursue.”
Scientists have long thought that hematopoietic stem cells (HSCs) are regulated similarly in males and females.
But research conducted in mice has shown that HSCs exhibit sex differences in cell-cycle regulation.
The researchers discovered that HSCs in female mice divided significantly more frequently than HSCs in male mice, and this appeared to be driven by estrogen.
Sean Morrison, PhD, of UT Southwestern Medical Center in Dallas, and his colleagues detailed these discoveries in a letter to Nature.
The research suggested that differences in HSC division depend on the ovaries and not the testes. When the investigators administered estradiol, a hormone produced mainly in the ovaries, to male and female mice, HSC division increased in both sexes.
And experiments in pregnant mice highlighted the importance of estrogen in HSC activity. Estrogen levels increased during pregnancy, which increased HSC division, HSC frequency, cellularity, and erythropoiesis in the spleen.
“Elevated estrogen levels that are sustained during pregnancy induce stem cell mobilization and red cell production in the spleen, which serves as a reserve site for additional red blood cell production,” Dr Morrison said.
He and his colleagues also found that HSCs expressed high levels of estrogen receptor-alpha. And deleting the receptor reduced HSC division in female mice but not in males.
In pregnant mice, deleting the receptor attenuated the previously observed increases in HSC division, HSC frequency, and erythropoiesis.
These results suggest estrogen acts directly on HSCs to increase their proliferation and the number of red blood cells they generate.
“If estrogen has the same effect on stem cells in humans as in mice, then this effect raises a number of possibilities that could change the way we treat people with diseases of blood cell formation,” Dr Morrison said.
“Can we promote regeneration in the blood-forming system by administering estrogen? Can we reduce the toxicity of chemotherapy to the blood-forming system by taking into account estrogen levels in female patients? Does estrogen promote the growth of some blood cancers? There are numerous clinical opportunities to pursue.”