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Lifting the Differentiation Embargo

Effective differentiation therapy for acute myeloid leukemia (AML) has been restricted to a small subset of patients with one defined genetic abnormality. Using an unbiased small molecule screen, Sykes et al. now identify a mechanism of de-repression of differentiation in several models of AML driven by distinct genetic drivers.

2016-09-23

Evidence for Pro-angiogenic Functions of VEGF-Ax

Contrary to a previous report, VEGF-Ax does not possess anti-angiogenic properties.

2016-09-23

Editing DNA Methylation in the Mammalian Genome

DNA methylation patterns can be specifically altered in mammalian cells using CRISPR/Cas9-based approaches.

2016-09-23

Timeline: Cellular Oxygen Sensing

Since the 1950s, researchers have recognized that red blood cell numbers expand or contract as needed, according to the amount of available oxygen. The later discoveries that erythropoietin and VEGF levels adapt to oxygen levels launched a new field aimed at understanding how cells sense and respond to normal- and low-oxygen environments. The 2016 Albert Lasker Basic Medical Research Award recognizes key discoveries about this global oxygen sensing pathway and its impacts on pathogenesis, including cancer and inflammation.

2016-09-23

Timeline: Targeted Treatment of Hepatitis C Virus

Chronic hepatitis C virus infection can cause liver cirrhosis and cancer, and early treatment options were non-specific and could be toxic. Work aimed at elucidating the viral life cycle has led to better treatment options through the development of direct-acting antivirals, as exemplified by the work of Ralf Bartenschlager, Charles Rice, and Michael Sofia who have received the Lasker∼DeBakey Clinical Medical Research Award for their work on this effort. Key events in understanding HCV replication and development of direct-acting antivirals are shown in this Timeline.

2016-09-23

Central Control Circuit for Context-Dependent Micturition

How are olfactory and social cues integrated in the mouse brain to control where and under what circumstances mice urinate?

2016-09-23

Large-Scale Movements of IF3 and tRNA during Bacterial Translation Initiation

Bacterial ribosomes can start scanning for start codons only after undergoing large scale conformational changes governed by three key initiation factors.

2016-09-23

Structural Basis for Gating and Activation of RyR1

Cryo-EM studies of the open and closed forms of the ryanodine receptor RyR1 in response to multiple activators provide the structural basis for its gating and activation

2016-09-23

Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation

Gain-of-function mutations in the inflammasome sensor NLRP1 increase susceptibility to skin cancer and unmask unique regulatory autoinhibition in the inflammasome.

2016-09-23

sRNA-Mediated Control of Transcription Termination in E. coli

Bacterial small RNAs balance the Rho-dependent termination pathway to prevent premature transcription termination, extending the role of these RNA regulators beyond post-transcriptional control.

2016-09-23

Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing

Transient co-expression of engineered transcriptional repressors (ETRs) allows for stable and highly specific epigenetic silencing of endogenous genes, which is amenable to multiplexing and can be reverted by targeted DNA demethylation.

2016-09-23

Structured States of Disordered Proteins from Genomic Sequences

Sequence couplings reveal structural states of flexible and disordered proteins.

2016-09-23

Portable, On-Demand Biomolecular Manufacturing

Ready-to-use preparations enable on-site, on-demand production of biomolecules like antimicrobials and vaccines without refrigeration or specialized equipment.

2016-09-23

A New Handle for a Hot Topic: Genetic Markers for Warm-Sensing

Stepping out of an aggressively air-conditioned building into the sweltering heat evokes a number of thermoregulatory responses, both autonomic (sweating) and behavioral (peeling off a layer of clothing or seeking an iced beverage). Just as we come out of the hottest part of the summer, a study by Tan and colleagues provides an exciting breakthrough in our understanding of and ability to study the neural mechanisms of keeping cool when it’s hot.

2016-09-23

When a Stomach Bug Comes Calling

They say that an army marches on its stomach, and while history provides ample illustration of the value of robust supply lines, the quality of the stores being delivered matters equally. In our modern world (where a growing population is truly an army writ large), food safety is of paramount importance for human health and economic stability. Viral and bacterial gastrointestinal infections transmitted from individual to individual during food preparation or from compromised food sources directly can be acutely debilitating and even fatal for subsets of the population, including young children.

2016-09-23

Into Thin Air: How We Sense and Respond to Hypoxia

This year’s Lasker Basic Medical Research Award is shared by William Kaelin, Peter Ratcliffe, and Gregg Semenza for discovery of the pathway by which cells sense and adapt to changes in oxygen availability, which plays an essential role in human adaptation to a wide variety of physiologic and pathologic conditions.

2016-09-23

An Addiction to Education at All Levels

I grew up long before the Internet, at a time when there was hardly anything of interest to watch on our tiny black and white television—in fact, the available TV channels would mostly display “test patterns.” As a result, school was by far the most interesting activity in my life; in comparison, the hot, humid summer vacation months, spent at home near Chicago without air conditioning, seemed endlessly boring. Later, accumulating the 21 Boy Scout merit badges needed for Eagle rank would fill my summers much more productively—a model that I have suggested schools might use today, to allow students to get credit for deeply exploring a few of their individual passions.

2016-09-23

Pioneering a Global Cure for Chronic Hepatitis C Virus Infection

This year’s Lasker∼Debakey Clinical Medical Research Award honors Ralf Bartenschlager, Charles Rice, and Michael Sofia, pioneers in the development of curative and safe therapies for the 170 million people with hepatitis C virus infection.

2016-09-23

The Rule of Three for Prizes in Science and the Bold Triptychs of Francis Bacon

For many scientific awards, such as Nobels and Laskers, the maximum number of recipients is three. This Rule of Three forces selection committees to make difficult decisions that increase the likelihood of singling out those individuals who open a new field and continue to lead it. The Rule of Three is reminiscent of art’s three-panel triptych, a form that the modern master Francis Bacon used to distill complex stories in a bold way.

2016-09-23
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