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This year's Lasker DeBakey Clinical Research Award goes to Napoleone Ferrara for the discovery of vascular endothelial growth factor (VEGF) as a major mediator of angiogenesis and for the development of an effective anti-VEGF therapy for wet macular degeneration, a leading cause of blindness in the elderly.
This year, the Albert Lasker Basic Medical Research Award will be shared by Douglas Coleman and Jeffrey Friedman for their discovery of leptin, a hormone that regulates appetite and body weight. By uncovering a critical physiologic system, their discovery markedly accelerated our capacity to apply molecular and genetic techniques to understand obesity.
Spatial distribution of the plant hormone auxin regulates multiple aspects of plant development. These self-regulating auxin gradients are established by the action of PIN auxin transporters, whose activity is regulated by their constitutive cycling between the plasma membrane and endosomes. Here, we show that auxin signaling by the auxin receptor AUXIN-BINDING PROTEIN 1 (ABP1) inhibits the clathrin-mediated...
Aneuploidy causes a proliferative disadvantage in all normal cells analyzed to date, yet this condition is associated with a disease characterized by unabated proliferative potential, cancer. The mechanisms that allow cancer cells to tolerate the adverse effects of aneuploidy are not known. To probe this question, we identified aneuploid yeast strains with improved proliferative abilities. Their molecular...
Maintenance of skeletal muscle structure and function requires innervation by motor neurons, such that denervation causes muscle atrophy. We show that myogenin, an essential regulator of muscle development, controls neurogenic atrophy. Myogenin is upregulated in skeletal muscle following denervation and regulates expression of the E3 ubiquitin ligases MuRF1 and atrogin-1, which promote muscle proteolysis...
This year's Lasker-Koshland Special Achievement Award in Medical Science is conferred on Sir David Weatherall for his 50 years of dedication to biomedical research, his groundbreaking discoveries about genetic blood diseases, and his life-long passion for bringing improved medical care to the developing world.
Activation-induced cytidine deaminase (AID) initiates antibody gene diversification by creating U:G mismatches. However, AID is not specific for antibody genes; Off-target lesions can activate oncogenes or cause chromosome translocations. Despite its importance in these transactions little is known about how AID finds its targets. We performed an shRNA screen to identify factors required for class...
Aneuploidy, or an abnormal number of chromosomes, adversely affects cell growth, but it is also linked with cancer and tumorigenesis. Now, Torres et al. (2010) help to resolve this paradox by demonstrating that aneuploid yeast cells can evolve mutations in the proteasome protein degradation pathway that alleviate imbalances in protein production and increase the cell's proliferative capacities.
We report the generation and comparative analysis of genome-wide chromatin state maps, PPARγ and CTCF localization maps, and gene expression profiles from murine and human models of adipogenesis. The data provide high-resolution views of chromatin remodeling during cellular differentiation and allow identification of thousands of putative preadipocyte- and adipocyte-specific cis-regulatory elements...
While the long noncoding RNAs (ncRNAs) constitute a large portion of the mammalian transcriptome, their biological functions has remained elusive. A few long ncRNAs that have been studied in any detail silence gene expression in processes such as X-inactivation and imprinting. We used a GENCODE annotation of the human genome to characterize over a thousand long ncRNAs that are expressed in multiple...
Auxin is a multifunctional hormone essential for plant development and pattern formation. A nuclear auxin-signaling system controlling auxin-induced gene expression is well established, but cytoplasmic auxin signaling, as in its coordination of cell polarization, is unexplored. We found a cytoplasmic auxin-signaling mechanism that modulates the interdigitated growth of Arabidopsis leaf epidermal pavement...
Symmetry lies at the core of bilaterian development. Although mostly maintained, in some circumstances it is broken purposefully to create asymmetric structures, such as the heart. Recent discoveries reveal previously unappreciated strategies for maintaining or breaking symmetry in flies, nematodes, zebrafish, and mice and explore the functional consequences of disrupting these morphogenetic processes.
Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at the small intestinal crypt base and divide every day. We have carried out fate mapping of individual stem cells by generating a multicolor Cre-reporter. As a population, Lgr5 hi stem cells persist life-long, yet crypts drift toward clonality within a period of 1–6 months. We have collected short- and...
Regeneration of transected peripheral nerves is a complex process involving the coordinated action of neuronal axons, glial cells, and fibroblasts. Using rodent models of nerve repair, Parrinello et al. (2010) find that ephrin signaling between fibroblasts and Schwann cell progenitors, involving the stemness factor Sox2, is required for nerve regeneration.
The coordinated growth of epidermal cells in plant leaves creates the characteristic jigsaw puzzle appearance of the pavement cells. Now, Xu et al. (2010) report that AUXIN-BINDING PROTEIN 1 mediates auxin activation of two GTPase pathways that antagonistically control planar morphogenesis of leaf epidermal cells to create this distinctive pattern.
This Essay explores the notion that specialized cells have unique vulnerabilities to environmental contingencies that microRNAs help to counteract. Given the ease with which new microRNAs evolve, they may serve as ideal facilitators for the emergence of new cell types.
Ca 2+ is an essential and ubiquitous second messenger. Changes in cytosolic Ca 2+ trigger events critical for tumorigenesis, such as cellular motility, proliferation, and apoptosis. We show that an isoform of Secretory Pathway Ca 2+ -ATPase, SPCA2, is upregulated in breast cancer-derived cells and human breast tumors, and suppression of SPCA2 attenuates basal Ca 2+ ...
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