Scizzling Papers of the Week - January 3rd

The Scizzle Team

Marking malaria resistance

Worldwide elimination of malaria is finally starting to appear possible, thanks in part to widely successful treatments such at artemisinin-based combinations, but a rising incidence of artemisinin-resistant malaria parasites in parts of southeast Asia.  To curtail this trend, and identify where it has already struck, requires a molecular marker for such resistance, which has now been discovered.  Investigators identified a mutation in the ketch protein K13 that is seen in various artemisinin-resistant populations, but not in parasites sensitive to the drug.  Ecological surveys showed that this mutation was found in parasites from affected areas, but rare in regions with few cases of resistance; indeed, this marker was more reliable than population grouping in predicting parasites’ drug sensitivity.

A molecular marker of artemisinin-resistant Plasmodium falciparum malaria, Ariey et al, Nature, 2 January 2014.

 

Neanderthal genome hints at a new player

Researchers have completed the first high-quality genome sequence of a Neanderthal, discovering that her parents were half-siblings and that in her recent ancestry, mating of closely related individuals was fairly common.  The investigators were also able to improve upon prior estimates of the degree of genetic contribution from Neanderthals in modern humans, and gained insight into gene flow among Neanderthals, Denisovans (another archaic group) and early modern humans.  Finally, their evidence suggests gene flow into Denisovans from another, as yet unidentified group.

The complete genome sequence of a Neanderthal from the Altai Mountains, Prüfer et al, Nature, 2 January 2014.

 

An intoxication inhibitor

The supposedly inactive precursor of neurosteroid hormones, pregnenolone, may play a role in protecting the brain during cannabis exposure.  Pregnenolone levels in rodents went up following injection of most major drugs of abuse, but by far the greatest effect was seen following administration of THC.  Prenenolone, in turn, inhibited activity of the CB1 receptor, which mediates the effects of THC, thus reducing their severity.  Such a negative feedback loop may help guard the brain during exposure to THC, and might be helpful in treating cannabis intoxication.

Pregnenolone can protect the brain from cannabis intoxication, Valleé et al, Science, 3 January 2014.

 

Researchers shed new light on gamma-ray burst

The explosion of a massive star last spring caused the largest gamma-ray burst ever recorded.  This week, several different research groups have published their analyses covering various aspects of the event, including indications that current models cannot account for all aspects of the explosion.

An exceptionally bright gamma-ray burst, Fynbo, J.P.U., Science, 3 January 2014


Sizzling Papers of the Week - Dec 13

 

The Scizzle Team

I’m Melting!  Melting snow and ice underlie extreme summer weather

Extreme summer weather has been on the rise this decade, while snow cover and sea ice have been declining - but how these were connected has remained a mystery.  Now, by combining satellite observation of snow and ice cover with atmospheric data, researchers have been able to demonstrate an association between the shrinking cryosphere and changes in atmospheric circulation, including reduced high latitude winds, a shifted jet stream, and more.  Loss of sea ice appears to have a stronger effect, even though this occurs at a lesser rate than snow loss.

Extreme summer weather in northern mid-latitudes linked to a vanishing cryosphere, Tang, Q. Zhang, X. and Francis, J.A., Nature Climate Change. December 12 2013

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Immune cells beat brain tumors

In the brain, tumors are often spurred by brain tumor initiating cells or BTICs.  Now, there may be a way to help stop BTICs’ action.  When macrophages or microglia from non-glioma humans were applied to BTICs in culture, the immune cells induced the expression of genes that stop the cell cycle, thus halting the progression of BTICs - an effect that was not seen when immune cells from glioma patients were used.  This action of microglia was enhanced by amphotericin B (AmpB); daily administration of the drug prolonged the life of animals with BTICs and the drug helped glioma-derived immune cells act like their healthier counterparts in fighting the tumor initiator cells.

Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells, Sarkar, S. et al., Nature Neuroscience. December 8 2013.

Want to stay on top of  macrophages beating BTICs? Create a feed for BTIC, macrophages and glioma.  And read more in out earlier blog post on How Tumors Prosper in the Brain.

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Did ancient lungs have one way signs?

It was long thoughts that unidirectional flow in the lungs was the purview of birds, specialized for the demands of flying; then crocodilians were found to share this trait, suggesting that this airflow pattern may be as old as the Triassic period when birds and crocodilians split.  Now, investigators have shown that the savannah monitor lizard (Varanus exanthematicus) also share a unidirectional lung system.  This finding suggest that either the monitor lizards evolve this system independently, or unidirectional airflow it been around far longer than scientists thought, hailing from the Palaeozoic era.

Unidirectional pulmonary airflow patterns in the savannah monitor lizard, Schachner, E.R., et al., Nature. December 11 2013

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Who would like to chaperone this misfolded protein?

Gene mutations can lead to misfolded proteins, but just because they weren't folded correctly doesn't mean they aren't functional. What renders misfolded proteins useless is their mis-routing by the cell, as these usually get stuck in the ER. However, a paper published in PNAS this week offers a brilliant solution - pharmacoperones - small molecules that will enter the cell, "correct" the protein and make sure it's routed correctly. Using this technique, the researchers were able to restore the function of a mutant gonadotropin releasing hormone receptor (GnRHR) and by doing so restored the ability of the mice to have offspring. If this new technique can work in people, it will open the door to curing diseases ranging from cystic fibrosis to Alzheimer's disease.

Restoration of testis function in hypogonadotropic hypogonadal mice harboring a misfolded GnRHR mutant by pharmacoperone drug therapy. Janovick et al., PNAS. December 2013.

Want to know on advances using pharmacoperones? Create a feed for pharmacoperones and another feed for following the senior author of the study Conn P.M.

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Sizzling Papers of the Week - Dec 6

 

The Scizzle Team

 

Genetics don't lie

A cave in Spain - Sima de los huesos - had he largest collections of hominin bones. Now mitochondrial DNA from a femur bone collected from the cave in the 1990s was sequenced. It was believed that the bones found in Sima de los huesos were of Neanderthals but the DNA sequence suggests otherwise and left the researchers bewildered: the phylogenetic analysis showed that the DNA is closer to Denisovans than to Neanderthals - a population believed to live in southwestern Siberia. So the mystery of where our ancestors came from still remains and only more sequencing of ancient DNA will help solve it.

A mitochondrial genome sequence of a hominin from Sima de los huesos. Meyer at al., Nature. 2013.

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Future of genome therapy is looking CRISPR

Two studies published in Cell Stem Cell using the CRISPR-Cas9 system to cure diseases in mice and human stem cells.  They CRISPR/Cas9 system was originally discovered as the "immune system" of archaea and bacteria.  In the first study  the system was used in mice to correct the Crygc gene that causes cataracts; in the second study the CRSPR-Cas9 system was used to correct the CFTR locus in cultured intestinal stem cells of CF patients. These findings serve as a proof-of-concept that diseases caused by a single mutation can be "fixed" with genome editing using the CRISPR-Cas9 system.

Correction of genetic disease in mouse via use of CRISPR-Cas9. Wu et al. Cell Stem Cell. 2013.

Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of Cystic Fibrosis patients. Schwank et al., Cell Stem Cell. 2013.

Want to stay on top of  the CRISPR/Cas9 genome editing and curing diseases? Create a feed for CRISPR, Cas9 and diseases.

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You smell so good!

After being traumatized by what really happens inside you when a mosquito bites we thought there's no hope that we'll ever be mosquito-bite free. But a new study published in Cell opens the door to new, safe and pleasantly smelling way to lure mosquitoes away. The female mosquito detects CO2 using a class of olfactory receptor neurons, but the neurons and receptors that detects skin odor are a mystery. The researchers found  one neuron important for attraction to skin odor and then screened half a million compounds to find those who lured mosquitoes to traps effectively as CO2 does. Joking aside, finding safe and affordable ways to control mosquitoes is a key way to preventing them from transferring deadly diseases.

Targeting a dual detector of skin and CO2 to modify mosquito host seeking. Tauxe et al. Cell. 2013.

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It Runs in the family

Scientists showed that behavioral experiences can shape mice epigenetically in a way that is transmittable to offspring.  Male mice conditioned to fear an odor showed hypomethylation for the respective odor receptor in their sperm; offspring of these mice showed both increased expression of this receptor, and increased sensitivity to the odor that their fathers had been conditioned on.  Does this suggest that memories can be inherited?

Parental olfactory experience influences behavior and neural structure in subsequent generations, Dias, B.G. and Ressler, K.J., Nature Neuroscience. Published online December 1st 2013

Fascinated by the possibility of inheriting memories? Create a feed for epigenetics and memory and don't miss our post about this article and all the buzz -  family fear?

A pathway for the worst sides of addiction?

Opioid drugs, such as heroin, appear to have a specific pathway mediating some of the worst aspects of addiction; the κ opioid receptor is involved the dysphoria of withdrawal and the need to constantly increase dosage.  Inhibiting the κ receptor blocked dosage escalation in rats and reduced their motivation to administer the drug.  This receptor pathway may be crucial to the urge to avoid withdrawal, which itself is a powerful component of addiction.

Long-Term Antagonism of κ Opioid Receptors Prevents Escalation of and Increased Motivation for Heroin Intake, Schlosburg, J.E, et al., The Journal of Neuroscience. December 4 2013

From bacteria to behavior

Is there anything gut bacteria can't do?  A new study this week shows that the little critters may have a role in ameliorating autism.  It's been known for some time that autistic individuals are more likely to suffer various gastrointestinal problems.  Researchers found that a mouse model for autism suffers from gut inflammation similar to that seen in colitis.  The bacteria B. fragilis, which has been show to help repair these symptoms in illnesses such as Chrons disease. help repair the autistic mice's intestines as well.  More amazingly, treatment with the bacteria also improved behavioral symptoms of autism.

Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopment Disorders, Hsiao, E.Y., et al., Cell. 2013.

Stay on top of the growing list of things we can thank or blame gut microbiota for? Create a feed for gut microbiota.

It wasn't my fault...line

Japan's Tohoku-Oki earthquake in 2011 was not only devastating, but in many ways surprising even to scientists.  Investigators are striking back in a full throttle attempt to glen information about the fault zone implicated in the 2011 quake.  A collection of papers published this week in Science characterize the fault zone's structure and composition, examined the physics underlying slippage during the quake, and tracked the physical conditions and stresses that the fault zone is exposed to, allowing an unprecedented understanding of the underlying causes of this natural disaster.

Chester et al, Ujiie et al, and Fulton et al   Science. December 6 2013.


Sizzling Papers of the Week - Nov 29

 

The Scizzle Team

 

Choices, Choices…

The decisions we make are influenced not only by the objective pros and cons of each option, but also by subjective evaluations that lead us to prefer one choice over another.  Research published Monday suggested that the home of such subjective preferences in the brain may be the lateral habenula, a region previous thought to be more generally involved in aversion.  Interfering with the lateral habenula’s functioning left rats unable to use subjective preferences, such as favoring large rewards that require more work or small, more easily obtained rewards - to guide their choices, instead reverting to choosing at random.

What's better for me? Fundamental role for lateral habenula in promoting subjective decision biases , Stopper, Colin M and Floresco, Stan B., Nature Neuroscience, advance online publication November 24 2013

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Cholesterol and Breast Cancer Tag Team

High cholesterol and breast cancer are both leading health threats - and now investigators have discovered how the two can work together.  A metabolite of cholesterol, 27HC, increases certain forms of tumor growth and metastasis, an effect that depends on conversion by the cytochrome oxidase CYP27A1.  It turns out that CYP27A1 levels correlate to tumor grade, and inhibiting CYP27A1 reduces the influence of high cholesterol on breast cancer.

27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology, Nelson, Erik R., et a.l, Science, November 29 2013

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It's All in Your Gut (but we're not talking bacteria this time)

Love can we blind but your visceral isn't! A 4-year study found that the visceral attitudes, that are not necessary all sweet, can predict if the couple is indeed the "happily ever after" kind of marriage or not. So before you decide to get married - check you gut feeling.

Though They May Be Unaware, Newlyweds Implicitly Know Whether Their Marriage Will Be Satisfying. McNulty JK et al., Science. 2013.

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Don't Worry, Be Happy

Psychoneuroimmu...what? psychoneuroimmunology (PNI). This week Nature took a closer look at the field of PNI which aims to understnad how the nervous and the immune systems interact with each other, or in other words - how one's mental state can affect the whole body and his/ her health. See how one biologist is trying to tackle this question by sound science.

Immunology: The Pursuit of Happiness. Marchant J. Nature. 2013.

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Sizzling Papers of the Week - Nov 22

 

The Scizzle Team

Guys, Stop Fighting Over Me!

Male-male aggression is part of sexual selection in many species, and is affected by environment, experience, and the animal’s state - but how?  Researchers found that while male fruit flies will usually be at each others’ throats when an eligible [fly] bachelorette is around, this fighting is reduced in males who’ve had prior exposure to the ladies.  Turns out the male flies can sense females via a special pheromone-sensing  ion channel, triggering activity in a pathway mediated by the inhibitory neurotransmitter GABA which quells male aggression.  Thus, this new found circuit represents a key means for experience to modulate aggression.

 

Female contact modulates male aggression via sexually dimorphic gABAergic circuit in Drosophila, Yuan Q. et al., Nature Neuroscience, November 17, 2013

Create a feed for gABAergic circuit to keep up with all the fighting.

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Another Reason to Love Germs

You know how when you tell distant family members you’re a scientist, there’s always someone who asks whether you’re curing cancer?  Well it turns out the millions of microbiota living in your gut can answer that question with a resounding “yes.”  These little guys can have a big effect on inflammation, which in turn plays an important role in cancer.  Investigators found that when mice lack a robust host of microorganisms, they responded less well to cancer therapies.  Way to go bacteria!

 

Commensal Bacteria Control Cancer Response to Therapy by Modulating the Tumor Microenvironment, Iida, N. et al., Science, November 21 2013

Create a feed for bacteria, microenviroment and cancer. 

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If Only We Could Remember What This Paper Was About...

With the medical use of marijuana on the rise, it’s more important than even to understand the mechanisms of unwanted side effects.  Researchers made important strides in clarifying how marijuana effects memory when they discovered that ∆9-THC, the active component in the plant, induces the activity of the enzyme COX-2 via CB1 receptors.  Blocking COX-2 reduces the negative impacts of ∆9-THC on memory, while permitting the medicinal effects such as reducing neurodegeneration in Alzheimer’s disease.

 

9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signalling, Chen, R. et al., Cell, November 17 2013.

Fascinated by marijuana? Create a feed for marijuana, COX-2 and memory.

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Taking a Closer Look at Chromosomes

We know that mitotic chromosomes are critical to cell division, but there remains a lot of doubt about precisely how these structures organize.  Now investigators have used chromosome conformation capture methods to shed more light on the issue.  They demonstrated that the way nonsynchronous cell were believed to organize is actually only true in interphase, while a more homogenous, consistent organization occurs during metaphase.  Simulations went on to show that classical models don’t correctly explain the organization of chromosomes during mitosis.

 

Organization of the Mitotic Chromosome, Naumova, N., et al., Science, November 21 2013

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Are You Cold?

Apparently, the mandated temperatures in which lab mice are kept are too cold for them and suppress their anti-tumor immune response. A new study published in PNAS shows that when mice were kept in thermoneutral temperatures, there were fewer immunosuppressive cells with significantly enhanced CD8+ T cell-dependent control of tumor growth. This study highlights the importance of the environmental temperature conditions and show how it may lead to a misunderstanding of anti-tumor immune response and its effect when studying potential anti-cancer therapies.

Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature. Kokolus KM et al., PNAS, November 2013.

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Sizzling Papers of the Week

 

The Scizzle Team

 

Mechanism for Immuno-suppressive Drug Explained

Why cyclophosphamide - a drug usually given after bone-marrow transplant (and best known for its use as a chemotherapy agent) is so effective against Graft-vs-Host Disease is sort of a mystery. A new paper in Science Translational Medicine shows that the effectiveness of cyclophosphamide depends on Treg, who are resistant to the drug and in their absence - cyclophosphamide loses its protective effect against GVHD.

Aldehyde Dehydrogenase Expression Drives Human Regulatory T Cell Resistance to Posttransplantation Cyclophosphamide.  Kanakry C.G. et al. Science Translational Medicine. November 2013.

To stay on top of the role of Treg in GVHD we suggest creating a feed for: cyclophosphamide, Treg and GVHD.

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Dogs' Family Tree Demystified

Where did domestic dogs come from, and when?  Evidence has been conflicting, with genetics suggesting an East Asian origin about 15,000 years ago, while the oldest known fossils resembling dogs are over 30,000 years old and found in Europe and Siberia.  Investigators collected mitochondrial DNA from some of these doglike fossils and compared this to DNA of modern domestic dogs and found that all modern dogs are most similar genetically to either ancient European dogs or other modern-day European canids, suggesting that Man's Best Friend was developed from the wolves that roamed Europe thousands of years ago.

Complete Mitochondrial Genomes of Ancient Canids Suggest a European Origin of Domestic Dogs. Thalmann O. et al., Science. 15 November 2013.

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Keeping an Eye on Earth's Forests

Deforestation is something of an environmental buzzword, but global change in forest cover has actually been rather poorly documented.  Now, using high resolution satellite data, investigators are able to examine how forests have developed over the last twelve years.  The result reveal a high degree of fluctuation, including both losses and gains, but an overall decline in forest area.

High-Resolution Global Maps of 21st-Century Forest Cover Change. Hansen M.C. et al., Science. 15 November 2013.

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This bacteria will self-destruct in....

Beyond the widely spread antibiotic-resistant bacteria is another, equally challenging, problem: antibiotic-tolerant bacteria. In chronic infections, the bacterial population produces a small number of dormant persister cells that give biofilm their antibiotic-tolerance properties. A new study published in Nature shows that acyldepsipeptide antibiotic activates ClpP protease in a non-specific way, leading to the degradation of 400 proteins within the persisters cells, forcing them to self-digest. These findings open the door for developing new and effective therapies against chronic infections.

Activated ClpP kills persisters and eradicates a chronic biofilm infection. Conlon B.P. et al., Nature. 2013.

To stay on top of  how to deal with persister cells?  Create a feed for persister cells, antibiotic-tolerance or follow the senior author of this study K. Lewis.

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