2014 Top stories & breakthroughs

Betatrophin and a new hope for Diabetes

Professor Douglas Melton in his lab

A study published in Cell last year offered evidence that a hormone called betatrophin, or Angiopoietin-like protein 8 (ANGPTL8), could ramp up pancreatic β cell proliferation in a mouse model of insulin resistance. The results made quite a splash; the study’s authors—led by Doug Melton at Harvard University—even wrote that betatrophin treatment “could augment or replace insulin injections by increasing the number of endogenous insulin-producing cells in diabetics.” 

Early this month, Melton and his colleagues report a complex recipe that can transform either human ES cells or iPS cells directly into functional β cells. The breakthrough is based on more than a decade of tenacious work in Melton’s lab. He and his colleagues have painstakingly studied the signals that guide pancreas development, applying what they and others have found to develop a method that turns stem cells into mature β cells. “There’s no magic to this,” Melton says. “It’s not a discovery so much as applied developmental biology.” The protocol “is reproducible, but it is tedious,” Melton adds.

 The stem cells are grown in flasks and require five different growth media and 11 molecular factors, from proteins to sugars, added in precise combinations over 35 days to turn them into β cells. On the bright side, Melton says, the technique can produce 200 million β cells in a single 500 ml flask—enough, in theory, to treat a patient. Melton says the protocol seems to work equally well with ES and iPS cell lines. 

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Cutting HIV off

How about if we re-write the whole story?

Scientists have discovered a new technique using a 20-nucleotide strand of what's known as 'guide RNA' that basically goes into the cell, detects the HIV's genetic code, and cuts it out of the genome making it as if the HIV had never existed

As a retrovirus, HIV literally writes itself into the genome of the people it infects, which in turn programs a person's cells to make more viruses and thus remain infected. But a new human genome-editing technique has eradicated the virus from a human cell for the first time, in what could eventually function as an entirely new HIV treatment.

So far, true cures and vaccines for HIV have remained elusive (except for a few rare cases involving bone marrow transplants, as has just happened in two patients), in no small part because the HIV virus infects a cell with its RNA, which causes infected cells to implement it into the person's own genetic code. That's where a new technique, developed by Kamel Khalili and Wenhui Hu of Temple University, comes in.

This study was published in Proceedings of the National Academy of Sciences  

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Brazil Uses Technology To Fight Dengue

Aedes aegypti  larvae

Researchers from the UFMG (Universidade Federal de Minas Gerais) and USP (Universidade de São Paulo) are developing new, innovative and low-cost technologies that could help in fighting Dengue. A chemical cocktail prevents larvae to eat or breathe and an intelligent trap catches ' bad mosquitoes'

Understand how

Another study from  New Scientist,  reports that  GM-Mosquitoes will be raised and unleashed in a commercial scale for the first time in attempt to stop outbreaks of Dengue fever in Brazil.  

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A novel Approach To Prevent  Malaria

A study led by researchers from Johns Hopkins Bloomberg School of Public Health found that injecting a vaccine-like compound into mice was effective in protecting them from malaria. The findings suggest a potential new path toward the elusive goal of malaria immunization.

In their study, researchers used a virus containing genes that were encoded to produce an antibody targeted to inhibit P. falciparum infection. Up to 70 percent of the mice were protected from malaria-infected mosquito bites. In a subset of mice that produced higher levels of serum antibodies, the protection was 100 percent. 

The mice were tested a year after receiving a single injection of the virus and were shown to still produce high levels of the protective antibody. The approach is known as Vector Immuno Prophylaxis  or VIP

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Electronic cigarettes may help smokers quit

First introduced in 2006— e-cigarettes proponents have argued that the pen-shaped nicotine vaporizers could help cigarette smokers kick the habit.

Now, a review of the scientific literature conducted by the UK Cochrane Centre focused on  two randomized controlled trials, and considered data from 11 cohort studies, which compared people who were already trying to quit with and without e-cigarettes.

On balance, the data “suggests that electronic cigarettes can be helpful for stopping smoking and reducing cigarette consumption,” says lead author and behavioral scientist Hayden McRobbie of the Wolfson Institute of Preventive Medicine in London.

After 1 year, trial participants who used the devices were more than twice as likely (4% versus 9%) to successfully quit compared with those who used a nicotine-free placebo vaporizer.
Another 36% of e-cigarette users were able to reduce the number of traditional cigarettes they smoked by 50% or more. But 28% of placebo users also reduced their cigarette consumption by at least 50%, suggesting that some of the e-cigarette’s quitting power may be derived from the mere act of “smoking” it.

The Cochrane review looked for signs of serious adverse reactions to the e-cigarette therapy, but found none. That’s certainly not to say that e-cigarettes are completely harmless. “We don’t know the risk of long-term use yet,” McRobbie says Because there are so few studies investigating how well e-cigarettes work as a quitting tool, the review’s confidence levels are low and estimates for efficacy are likely to change

The Cochrane review calls for further study, specifically comparing e-cigarettes with other methods of quitting like the patch in terms of safety and efficacy.

Read more: http://bit.ly/1JPEzbZ

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References

Hayden McRobbie et al.: Electronic cigarettes for smoking cessation and reduction | The Cochrane library|  December 17  2014 | DOI: 10.1002/14651858.CD010216.pub2

Smokers are up to four times more likely to have blood cells with no Y chromosome than non-smokers

The study was conducted by molecular oncologist Jan Dumanski and statistician Lars Forsberg of Uppsala University in Sweden. They took advantage of data collected from three ongoing Swedish trials. The long-term studies are looking for associations between behavioral, lifestyle, or other traits and disease. As part of the studies, data and blood are collected periodically.

Dumanski and Forsberg compared the DNA in blood cells of smokers to nonsmokers in more than 6000 men and found that smokers are 2.4 to 4.3 times more likely to be missing Y chromosomes in their blood cells than non-smokers.

The only factors that correlated with high Y chromosome loss were age and smoking. The study was reported in Science.

A recent study found an association between Y chromosome loss and a shorter life span, as well as a higher risk of multiple cancers.

“the associations between Y chromosome loss and shortened life span and disease risk do need to be confirmed in other large long-term studies.” says Stephen Chanock, a cancer geneticist at the National Cancer Institute in Bethesda, Maryland

Dumanski and his colleagues are also planning follow-up studies to better understand how cellular Y chromosome deficiency might cause poor health.

Y chromosome damage caused by smoking appears to be reversible and dose-dependent. 

Meanwhile, there is some reassuring news for smokers.  

“Previous smokers were no more likely to have Y chromosome loss than those who have never smoked” Forsberg says, so it’s never too late to quit 

Read more: http://bit.ly/1xe6Cyh

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References

Jan P. Dumanski et al.: Smoking is associated with mosaic loss of chromosome Y | Science  | December 4 2014 | DOI: 10.1126/science.1262092

Want to quit drinking? Then Stop smoking!

What would happen if someone went through alcohol withdrawal while either continuing or quitting smoking?

That’s exactly what the researcher Kelly Cosgrove and her team from Yale University asked themselves. They studied 22 alcohol-dependent men and five alcohol-dependent women along with 20 men and five women who weren't addicted to alcohol. About three-fifths of both groups were smokers.

The alcoholic group were admitted into the Department of Veterans Affairs' Clinical Neuroscience Research Unit for a treatment program, during which doctors underwent PET scans to measure the availability of GABA-A receptors—basically, the number of spots where a GABA-A molecule could attach and do its work—in different parts of the brain.

Alcohol and nicotine dependence result from complex processes in the brain, involving a number of different chemicals, known as neurotransmitters, that help regulate signals sent from neuron to neuron and across regions of the brain. One known point of overlap between alcohol and nicotine addiction, is a neurotransmitter called gamma-aminobutyric acid A. GABA-A actually slows down signals as they spread through the brain, but it's thought that it underlies the particular kind of high one gets when drinking and that nicotine similarly stimulates production of the chemical.

Over a four-week period, alcohol withdrawal led to higher levels of GABA-A receptor availability in both smokers and non-smokers, and at the same time, cravings for alcohol declined in both groups. However, alcohol-dependent non-smokers' levels returned to that of the non-smoking controls by the end of four weeks, while alcoholic smokers' levels remained throughout the treatment period.

An additional analysis suggested that there was a connection between GABA-A receptor availability and cravings for alcohol, but only among smokers. Continued smoking during withdrawal interfered with the subsequent normalization of the GABA-A receptors and was associated with higher levels of craving, which may increase relapse risk

A study using rhesus monkeys found that nicotine didn't play a role in GABA-A receptor availability, so it seems it's not nicotine but rather an unknown component of tobacco smoke that's to blame

The article was published in Proceedings of the National Academy of Sciences.

Read more: http://bit.ly/1rfeyfL

References 

Nathan Collins: Smoking Might Make It Harder to Quit Drinking | Proceedings of the National Academy of Sciences. | December 01, 2014

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High-speed imaging of entire Drosophila embryonic development wins first place

Imaging of embryonic stage of  fruit fly using SiMView technology

A study published in nature methods back in June 2012, Raju Tomer et al. showed a novel high-speed in vivo imaging with SiMView technology, which recorded multiple views of the specimen simultaneously. SiMView data sets provided quantitative morphological information and enabled accurate automated cell tracking of an entire early embryo.

#WatchNowh  ttp://on.fb.me/1w05oze multiple views of Drosophila embryonic development, recorded in 30-second intervals over a period of 24 hours, starting three hours after egg laying. This simultaneous multi-view light-sheet microscopy technique may help reveal cell lineages, cell differentiation and whole-embryo morphogenesis, essential aspects of developmental biology.

#ReadMore in the original article http://bit.ly/1uP7p0W

#microscopy #imaging #developmental #biology

Drosophila melanogaster embryonic development 

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How brains see: connectomics

Imagine what it would be like to travel through the brain in a blood vessel… 

#WatchNow this Nature video http://youtu.be/0oNHukxz5rI 
to understand what the term #connectomics mean and how it would be possible to make a #brainmap of all the synapses. 
#ReadMore in the original article: http://dx.doi.org/10.1038/nature12450

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Retinal neurons titrate VEGF to limit neuronal vascularization

Drosophila melanogaster visual system halfway through pupal development,
showing retina (gold), photoreceptor axons (blue)

During development, neurons guide and attract blood vessels, and consequently, a parallelism and functional crosstalk is established.

A new study published in Cell, reports a particular neurovascular interaction in eye development and disease: VEGFR2, a critical endothelial receptor for VEGF, was more abundantly expressed in retinal neurons than in endothelial cells, including endothelial tip cells. Genetic deletion of VEGFR2 in neurons caused misdirected angiogenesis toward neurons, resulting in abnormally increased vascular density around neurons.

Further genetic experiments revealed that this misdirected angiogenesis was attributable to an excessive amount of VEGF protein around neurons caused by insufficient engulfment of VEGF by VEGFR2-deficient neurons. Moreover, absence of neuronal VEGFR2 caused misdirected regenerative angiogenesis in ischemic retinopathy. #ReadNow the original article:http://bit.ly/1APyR43

COMPOUND THAT HELPS CARNIVORES FIND THEIR PREY DISCOVERED

Cuon alpinus and prey

During a long time, we have lived by the assumption that, if we were in a forest, we'd better don't cut ourselves, because our blood would attract predators. But, what does the blood have to elicit such a behaviour?  Is it simply a special odour or a particular substance involved? Now we might have a better understanding of that response. 

Recent studies analysing the composition of volatiles in mammalian blood, an important prey-associated odor stimulus for predators, found the odorant trans-4,5-epoxy-(E)-2-decenal to evoke a typical “metallic, blood-like” odor quality in humans. Sara Nilsson and colleagues at the University of Linkoping assessed the behavior of captive Asian wild dogs (Cuon alpinus), African wild dogs (Lycaon pictus), South American bush dogs (Speothos venaticus), and Siberian tigers (Panthera tigris altaica) when presented with wooden logs that were impregnated either with mammalian blood or with the blood odor component trans-4,5-epoxy-(E)-2-decenal, and compared it to their behavior towards a fruity odor (iso-pentyl acetate) and a near-odorless solvent (diethyl phthalate) as control.

 

Researchers then watched the dog species to see which logs they showed an interest in and for how long. Both species were seen to frequently sniff and bite both the aldehyde and horse blood specimens, but showed no interest in the logs doped with the odourless solvent. The results demonstrate that a single blood odor component can be as efficient in eliciting behavioral responses in large carnivores as the odor of real blood, suggesting that trans-4,5-epoxy-(E)-2-decenal may be perceived by predators as a “character impact compound” of mammalian blood odor.

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References 

1 S Nilsson et al |  PLoS One | November 2014 | DOI: 10.1371/journal.pone.0112694

2 Matthew Gunther | Metallic blood smell attracts predators|CW |November 2014 | rsc.li/1wm17Hs 

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Rapid movements of a single-cell protozoan T. thermophila expressing GFP-scramblase and confined in a small pocket in agarose.
Watch now bit.ly/sqtermophilav1

BETATROPHIN FACES SCRUTINY

     

Islets of Langerhans are made of four different cell types.
The majority are insulin-producing beta cells (shown in green)

A study published in Cell last year offered evidence that a hormone called betatrophin, or Angiopoietin-like protein 8 (ANGPTL8), could ramp up pancreatic β cell proliferation in a mouse model of insulin resistance. [1] The results made quite a splash; the study’s authors—led by Doug Melton at Harvard University—even wrote that betatrophin treatment “could augment or replace insulin injections by increasing the number of endogenous insulin-producing cells in diabetics.” [2]

Early this month, Melton and his colleagues report a complex recipe that can transform either human ES cells or iPS cells directly into functional β cells. The breakthrough is based on more than a decade of tenacious work in Melton’s lab. He and his colleagues have painstakingly studied the signals that guide pancreas development, applying what they and others have found to develop a method that turns stem cells into mature β cells. “There’s no magic to this,” Melton says. “It’s not a discovery so much as applied developmental biology.” The protocol “is reproducible, but it is tedious,” Melton adds. The stem cells are grown in flasks and require five different growth media and 11 molecular factors, from proteins to sugars, added in precise combinations over 35 days to turn them into β cells. On the bright side, Melton says, the technique can produce 200 million β cells in a single 500 ml flask—enough, in theory, to treat a patient. Melton says the protocol seems to work equally well with ES and iPS cell lines. [3]

But a follow-up study by an independent group of researchers found that the hormone is not required for β cell function or growth. “The lack of expansion of the beta cell area could theoretically be due to simultaneous increases in replication and apoptosis frequencies. However, even if this were the case, it would not change our observation that Angptl8 overexpression did not increase beta cell area, contrary to what was reported by Yi et al. (2013),” Viktoria Gusarova of Regeneron Pharmaceuticals and her colleagues wrote in a Cell paper published October 23. [2]

 Melton’s group redid its experiments to see what might have caused the discrepancy, finding the same result as Gusarova’s team. The problem appears to have been variability in how the mice responded to betatrophin. “Some mice respond strongly to ANGPTL8/betatrophin expression but many do not” Melton and his colleagues wrote in a response article accompanying Gusarova’s study [2]____________________________________________________________________________________________________________

References

1 P. Yi  et al: Betatrophin: A hormone that controls pancreatic B cell proliferation,
Cell 153, 747-758 (5) (2013)  | doi: 10.1016/j.cell.2013.04.008

2 Diabetes 'Breakthrough' breaks up | The Scientist |27 October 2014 | ArticleTS

3 For diabetes, stem cell recipe offers new hope |Science | 9 October 2014 | ArticleSci

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A new evolutionary theory 

could explain the origins of eukaryotic cells

Scientists have long pondered the question of how simple "prokaryotic" cells, like bacteria, which are little more than a membrane-bound sack, evolved into more complex eukaryotic cells, which contain numerous internal membrane compartments. These compartments include the nucleus, which holds genetic information in the form of DNA; the endoplasmic reticulum, which shunts proteins and lipids around the cell; and mitochondria which act as the cell's powerhouse. The mitochondria also contain their own distinct DNA, which is one good indicator of their once having been separate organisms. The trouble is that no one has identified eukaryotic cells that are intermediate in complexity, making it much harder to know how they evolved. [1]

At present, the most widely accepted theory is that mitochondria derive from a bacterium that was engulfed by an archaeon (plural = archaea), a kind of prokaryote that looks similar to a bacterium but has many molecular differences. The eukaryotic membrane systems, including the nuclear envelope, then formed within the boundaries of this archaeal cell through the invagination of the outer membrane. This fits with much current data, but a few problems remain. Most significantly, no archaeal cells are known that invaginate membranes [1]

In his paper published in BMC biology, David Baum from the University of Wisconsin explains:

'' we invert the traditional interpretation of eukaryotic cell evolution. We propose that an ancestral prokaryotic cell, homologous to the modern-day nucleus, extruded membrane-bound blebs beyond its cell wall. These blebs functioned to facilitate material exchange with ectosymbiotic proto-mitochondria. The cytoplasm was then formed through the expansion of blebs around proto-mitochondria, with continuous spaces between the blebs giving rise to the endoplasmic reticulum, which later evolved into the eukaryotic secretory system. Further bleb-fusion steps yielded a continuous plasma membrane, which served to isolate the endoplasmic reticulum from the environment '' [2]

David Baum explains the differences between the outside-in and inside-out theories using a metaphor: "A prokaryotic cell can be thought of as a factory composed of one large, open building in which managers, machinists, mail clerks, janitors, etc. all work side by side. In contrast, a eukaryotic cell is like a factory complex, composed of a several connected work spaces: a single control room and specialize rooms for receiving, manufacturing, shipping, waste disposal, etc. The traditional theories propose that the factory complex arose when partitions were built within a single hangar-like building. The inside-out theory, in contrast, imagines that a series of extensions were added around an original core building -- now the control room -- while others functions moved out into new, specialized quarters. [1]

The inside-out theory provides an alternative framework by which to explore and understand the dynamic organization of modern eukaryotic cells. 

_______________________________________________________________________________

References

1 How did complex life evolve? The answer could be inside out | Science Daily | October 2014 | http://bit.ly/1wLN1En

2 David Baum, Buzz Baum: An inside-out origin for the eukaryotic cell, BMC biology, 12:76 (2014)

 |doi:10.1186/s12915-014-0076-2

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