Study sheds light on what causes cells to divide

When a rapidly-growing cell divides into two smaller cells, what triggers the split? Is it the size the growing cell eventually reaches? Or is the real trigger the time period over which the cell keeps growing ever larger?

A novel study published online today in the journal Current Biology has finally provided an answer to this long unsolved conundrum. And it's not what many biologists expected.

"How cells control their size and maintain stable size distributions is one of the most fundamental, unsolved problems in biology," said Suckjoon Jun, an assistant professor of physics and molecular biology at UC San Diego, who headed the research study with Massimo Vergassola, a professor of physics. "Even for the bacterium E. coli, arguably the most extensively studied organism to date, no one has been able to answer this question."

Finding a solution was more than a basic-science pursuit for the scientists, who pointed out that learning more about the triggers of cell division would enable researchers to better understand such processes as the runaway cell division that leads to cancer. To conduct the study, Jun and his colleagues developed a tiny device to isolate and physically manipulate individual genetic materials.

"It turned out that we can use this device to also follow the life history of thousands of individual bacterial cells for hundreds of generations," he said. "We looked at the growth patterns of the cells very, very carefully, and realized that there is something really special about the way the cells control their size."

"In our study, we monitored the growth and division of hundreds of thousands of two kinds of bacterial cells, E. coli and B. subtilis, under a wide range of tightly controlled steady-state growth conditions," said Jun. "This produced statistical samples about three orders of magnitude, or a thousand times better, than those previously available. We could thus pursue an unprecedented level of quantitative analysis."

The scientists found through their development of mathematical models that matched their experimental data that the growth of cells followed the growth law, essentially exponential growth based on a constant rate. But they also found to their surprise that cell size or the time between cell divisions had little to do with when the cells divided. Instead, to keep the distribution of different sized cells within a population constant, the cells followed what the researchers termed "an extraordinarily simple quantitative principle of cell-size control."

"Specifically, we showed that cells sense neither space nor time, but add constant size irrespective of their birth size," said Jun. "This 'adder' principle automatically ensures stability of size distributions."

"E. coli and B. subtilis are one billion years divergent in evolution, and they are the textbook examples of the diversity of molecular details for biological controls in different bacterial species. Thus, their sharing the same quantitative principle for size maintenance is a textbook level discovery."

Source:UNIVERSITY OF CALIFORNIA - SAN DIEGO

Egg and sperm race: Scientists create precursors to human egg and sperm

Scientists at the University of Cambridge working with the Weizmann Institute have created primordial germ cells - cells that will go on to become egg and sperm - using human embryonic stem cells. Although this had already been done using rodent stem cells, the study, published today in the journal Cell, is the first time this has been achieved efficiently using human stem cells.

When an egg cell is fertilised by a sperm, it begins to divide into a cluster of cells known as a blastocyst, the early stage of the embryo. Within this ball of cells, some cells form the inner cell mass - which will develop into the foetus - and some form the outer wall, which becomes the placenta. Cells in the inner cell mass are 'reset' to become stem cells - cells that have the potential to develop into any type of cell within the body. A small number of these cells become primordial germ cells (PGCs) - these have the potential to become germ cells (sperm and egg), which in later life will pass on the offspring's genetic information to its own offspring.

"The creation of primordial germ cells is one of the earliest events during early mammalian development," says Dr Naoko Irie, first author of the paper from the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge. "It's a stage we've managed to recreate using stem cells from mice and rats, but until now few researches have done this systematically using human stem cells. It has highlighted important differences between embryo development in humans and rodents that may mean findings in mice and rats may not be directly extrapolated to humans."

Professor Surani at the Gurdon Institute, who led the research, and his colleagues found that a gene known as SOX17 is critical for directing human stem cells to become PGCs (a stage known as 'specification'). This was a surprise as the mouse equivalent of this gene is not involved in the process, suggesting a key difference between mouse and human development. SOX17 had previously been shown to be involved in directing stem cells to become endodermal cells, which then develop into cells including those for the lung, gut and pancreas, but this is the first time it has been seen in PGC specification.

The group showed that PGCs could also be made from reprogrammed adult cells, such as skin cells, which will allow investigations on patient-specific cells to advance knowledge of the human germline, infertility and germ cell tumours. The research also has potential implications for understanding the process of 'epigenetic' inheritance. Scientists have known for some time that our environment - for example, our diet or smoking habits - can affect our genes through a process known as methylation whereby molecules attach themselves to our DNA, acting like dimmer switches to increase or decrease the activity of genes. These methylation patterns can be passed down to the offspring.

Professor Surani and colleagues have shown that during the PGC specification stage, a programme is initiated to erase these methylation patterns, acting as a 'reset' switch. However, traces of these patterns might be inherited - it is not yet clear why this might occur.

"Germ cells are 'immortal' in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next," adds Professor Surani. "The comprehensive erasure of epigenetic information ensures that most, if not all, epigenetic mutations are erased, which promotes 'rejuvenation' of the lineage and allows it to give rise to endless generations. These mechanisms are of wider interest towards understanding age-related diseases, which in part might be due to cumulative epigenetic mutations."

Source:Journal Cell

Most Popular Video of 2014 :Green Spaces Deliver Lasting Mental Health Benefits

In this video from the seventh most-visited release, Dr. Ian Alcock describes his research on how green spaces in towns and cities create immediate and long lasting improvements in people's well-being.
Credits:AAAS

New Genetic Anomalies Discovered in Lung Cancer

Patients whose tumors contained a large number of gene fusions had worse outcomes than patients with fewer gene fusions, according to researchers at the University of Michigan Comprehensive Cancer Center who analyzed the DNA and RNA of lung cancers. Gene fusions are a type of genetic anomaly found in cancers that occurs when genes get rearranged and fuse together. Researchers also identified several new genetic anomalies that occur in lung cancer, including in patients with a history of smoking.  

 

Study author Arul Chinnaiyan said, "Lung cancer is quite a complex disease with many causes. Our deep sequencing analysis found new gene fusions in lung cancers that were negative for the most commonly known fusions. These new anomalies could potentially be targets for developing new treatments."

Researchers studied 753 lung cancer samples that represented both smokers and non-smokers. They found 6,348 unique fusions with an average of 13 fusions per tumor sample. Anomalies in two gene pathways were most prevalent- the Hippo pathway, which has previously been linked to some rare cancers; and NRG1, which has not previously been linked to cancer. The researchers recommend expanding lung cancer subtypes based on these molecular characteristics.

The team suggests exploring these inhibitors as potential therapeutics in lung cancer. Pharmaceutical companies are already investigating drugs that could target the Hippo pathway and NRG1. Also, the finding that the number of gene fusions was linked to prognosis suggests that a screen could be developed to help doctors determine how aggressive a patient's tumor is likely to be and to personalize treatment accordingly.

Source:The study is published in 'Nature Communications'. 
 

Extra Vitamin E may Help Protect Against Pneumonia: Study

Recently, a new study has revealed that extra vitamin E may help protect against common type of Pneumonia in humans, as it showed promising results in protecting older mice from the disease.

 

Microbiologists and nutrition researchers from Tufts University reported that the extra vitamin E helped regulate the mice's immune system. 

The reduced numbers of bacteria and white blood cells resulted in less lung damage in the older mice who received extra vitamin E. These mice were able to control the infection as efficiently as young mice. 

A 2013 report on antibiotic resistance threats from the Centers for Disease Control and Prevention identified infections from Streptococcus pneumoniae as a serious concern that requires "prompt and sustained action." 

The bacterium causes 1.2 million drug-resistant infections, 19,000 excess hospitalizations, 7,000 deaths, and 96 million dollars in excess medical costs per year. Older adults and young children are at most risk for developing these drug-resistant infections. 
Source:
The study is published in the Journal of Immunology.
 

Indian regulatory system needs to be strengthened to improve clinical trial industry in India: Neuland labs CFO

As the clinical trial industry is facing lot of resistance in India, Industry experts are of the view that the Indian regulatory system should undergo massive reforms to contain unethical practices in clinical trials and should pave way to open up at least 10 per cent of global clinical trials in the country. According to N S Viswanathan, chief financial officer, Neuland Laboratories limited, the Indian drug regulatory system is very weak when compared to the US FDA, particularly in the clinical trials segment, the rules and protocols should be amended and strengthened so that it should not give any chance for the unscrupulous and rouge elements to take advantage of any loopholes in the regulations. “Unlike in the western world, in most cases the Indian researchers and clinical research organisations do not stick to their actual experimental results. They tend to manipulate it and try to match it with the standard values.  Because of this kind of mindset we are not able to invent new things. We need to change our mindset and should believe in ourselves and should be able to challenge the existing systems. At the same time the Indian regulatory system should also be reformed and all loopholes should be plugged to make it more transparent and accountable,” said the CFO. Though the country has a huge potential for clinical trial industry in India, the industry is facing lot of resistance both from rights groups and from the regulators.  Not just that, because of a few rouge elements involved in the clinical trial industry and the media is also responsible for blowing the issue out of proportion, the industry has lost lot of opportunities in the drug discovery. During the past 2 years the DCGI has not even given more than 50 approvals for clinical trials in India. It is right time that India needs to streamline its regulations and should pave way to open up at least 10 per cent of global clinical trial market in the country. “We should follow what is best in the world. Our regulations are driven by Supreme Court rather than science and its essence. The regulatory system needs to be strengthened and needs to incorporate ways and mechanisms to find black sheeps and rouges in the clinical trials. Particularly, there is a need for incorporating right compensation for the subjects on trial. Transparent regulatory system should evolve and each and every data pertaining to the subjects should be made available and should not give scope for any manipulation,” said the CFO. In the wake of international regulators like US FDA and EU issuing warnings and blacklisting the pharmaceutical units in India, it is high time that Indian regulatory system needs to be strengthened and should bring in more regulatory reforms in the drug control administration on the lines of international standards.

Source:Pharmabiz

Neuroscientists identify brain mechanisms that predict generosity in children

University of Chicago developmental neuroscientists have found specific brain markers that predict generosity in children. Those neural markers appear to be linked to both social and moral evaluation processes.

There are many sorts of prosocial behaviors. Although young children are natural helpers, their perspective on sharing resources tends to be selfish. Jean Decety, the Irving B. Harris Professor of Psychology and Psychiatry, and Jason Cowell, a postdoctoral scholar in Decety's Child NeuroSuite lab, wanted to find out how young children's brains evaluate whether to share something with others out of generosity. In this study, generosity was used as a proxy for moral behavior. The paper is published online by Current Biology and will appear in the Jan. 5, 2015 issue.

"We know that generosity in children increases as they get older," said Decety. He added that neuroscientists have not yet examined the mechanisms that guide the increase in generosity. "The results of this study demonstrate that children exhibit both distinct early automatic and later more controlled patterns of neural responses when viewing scenarios showing helping and harmful behaviors. It's that later more controlled neural response that is predictive of generosity."

The study included recording brain waves by EEG and eye tracking of 57 children, ages three to five, while they viewed short animations depicting prosocial and antisocial behaviors of cartoon-like characters helping or hurting each other. Following that testing, the children played a modified version of a scenario called the "dictator game." The children were given ten stickers and were told that the stickers were theirs to keep. They were then asked if they wanted to share any of their stickers with an anonymous child who was to come to the lab later that day.

The children had two boxes, one for themselves and one for the anonymous child. In an effort to prevent bias, the experimenter turned around while the child decided whether or how much to share. On average, the children shared fewer than two stickers (1.78 out of 10) with the anonymous child. There was no significant difference in sharing behavior by gender or age. The authors also found that the nature of the animations the children watched at the outset could influence the children's likelihood of behaving in a generous way.

The study shows how young children's brains process moral situations presented in these scenarios and the direct link to actual prosocial behavior in the act of generosity by sharing the stickers. "The results shed light on the theory of moral development by documenting the respective contribution of automatic and cognitive neural processes underpinning moral behavior in children," Decety concluded in the paper.

The developmental scientists found evidence from the EEG that the children exhibited early automatic responses to morally laden stimuli (the scenarios) and then reappraised the same stimuli in a more controlled manner, building to produce implicit moral evaluations.

"This is the first neuro-developmental study of moral sensitivity that directly links implicit moral evaluations and actual moral behavior, and identifies the specific neuro markers of each," said Decety. "These findings provide an interesting idea that by encouraging children to reflect upon the moral behavior of others, we may be able to foster sharing and generosity in them." Decety added that these findings show that, contrary to several predominant theories of morality, while gut reactions to the behavior of others do exist, they are not associated with one's own moral behavior, as in how generous the children were with their stickers.

Decety and Cowell are now conducting similar work with even younger children, ages 12 to 24 months, to look at when these neural markers for generosity emerge.

Source:UNIVERSITY OF CHICAGO