Notizie da 153 fonti
Someone doing a survey calls and asks: "How many times a week would you say you exercise?" What do you tell them? And would it be different if the survey was being done via text rather than telephone? [More]
( Geological Society of America ) Results of a new US Geological Survey study conclude that faults west of Lake Tahoe, Calif., referred to as the Tahoe-Sierra frontal fault zone, pose a substantial increase in the seismic hazard assessment for the Lake Tahoe region of California and Nevada, and could potentially generate earthquakes with magnitudes ranging from 6.3 to 6.9.
( NYU Langone Medical Center / New York University School of Medicine ) Researchers at NYU School of Medicine have, for the first time, identified a single gene that simultaneously controls inflammation, accelerated aging and cancer.
( McMaster University ) A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments. To test more than a dozen different compounds, McMaster researchers pioneered a fully automated robotic system to identify several drugs, including thioridazine.
Publication year: 2012 Source: Molecular Cell, Volume 46, Issue 4 Roy Parker The process of training new PhDs is complex and has significant dropout rates associated with loss of financial and time investments by the student, mentor, and program. One approach to improve graduate education is to make explicit the skills students need to develop and to put in place mechanisms to develop those skills.
Publication year: 2012 Source: Molecular Cell, Volume 46, Issue 4 Susanna Chiocca, Christian Seiser In the current issue of Molecular Cell, de la Vega et al. (2012) propose an intriguing model for HIPK2 posttranslational modifications in response to oxidative stress, explaining how HIPK2 can possess both prosurvival as well as proapoptotic activities.
Publication year: 2012 Source: Molecular Cell, Volume 46, Issue 4 Yoosik Kim, V. Narry Kim RNA silencing requires assembly of an effector complex, RNA-induced silencing complex (RISC), composed of a small RNA and the Ago protein. In this issue of Molecular Cell, Liu et al. (2012) provide insights of miRNP/RISC assembly pathways in mammals, using an in vitro human RISC assembly assay programmed by pre-miRNAs.
Publication year: 2012 Source: Molecular Cell, Volume 46, Issue 4 Seamus J. Martin, Conor M. Henry, Sean P. Cullen Members of the caspase family of cysteine proteases coordinate the morphological and biochemical events that typify apoptosis. However, neutralization of caspase activity in mammals fails to block death in response to most proapoptotic stimuli. This is because many cell death triggers provoke mitochondrial dysfunction upstream of caspase activation as a consequence of BAX/BAK channel opening. Although genetic or pharmacological inactivation of caspases fails to block cell death in most instances, it does convert the phenotype from apoptosis to necrosis. This has important implications for how the immune system responds to such cells, as necrotic cells provoke inflammation whereas apoptotic cells typically do not. Here, we propose an alternative perspective on apoptosis-associated caspase function by suggesting that these proteases are activated, not to kill, but to extinguish the proinflammatory properties of dying cells. This perspective unifies the mammalian caspase family as either positive or negative regulators of inflammation.
Publication year: 2012 Source: Molecular Cell, Volume 46, Issue 4 Vered Sasson, Irit Shachrai, Anat Bren, Erez Dekel, Uri Alon A gene can be said to be insulated from environmental variations if its expression level depends only on its cognate inducers, and not on variations in conditions. We tested the insulation of the lac promoter of E. coli and of synthetic constructs in which the transcription factor CRP acts as either an activator or a repressor, by measuring their input function—their expression as a function of inducers—in different growth conditions. We find that the promoter activities show sizable variation across conditions of 10%–100% (SD/mean). When the promoter is bound to its cognate regulator(s), variation across conditions is smaller than when it is unbound. Thus, mode of regulation affects insulation: activators seem to show better insulation at high expression levels, and repressors at low expression levels. This may explain the Savageau demand rule, in which E. coli genes needed often in the natural environment tend to be regulated by activators, and rarely needed genes by repressors. The present approach can be used to study insulation in other genes and organisms. Highlights ► Insulation is the sensitivity of a gene's induction curve to noncognate conditions ► lac operon and synthetic promoters show sizable variation between conditions ► Promoter occupancy by the cognate regulator increases insulation ► An activator provided better insulation at high expression, a repressor at low
Publication year: 2012 Source: Molecular Cell, Volume 46, Issue 4 Yina Zhu, Dominic van Essen, Simona Saccani Cell-type-specific control of gene expression is critical for the development of multicellular organisms. To investigate the mechanisms which underlie this, we have studied the regulation of the model genes Mdc and Il12b, whose stimulus-induced expression is tightly restricted to specific cells of the immune system. Surprisingly, we find that neither the promoter nor the enhancer sequences of these genes are sufficient to direct this cell-type specificity. Instead, the activities of upstream enhancers are repressed in nonexpressing cells by high levels of trimethylated H3K9 in their flanking regions. Genome-wide analysis indicates that this manner of regulation is shared by numerous enhancers of cell-type-specific genes. In dendritic cells and macrophages, the stimulus-induced demethylase Jmjd2d controls H3K9me3 levels at these regions, and is thereby required for Mdc and Il12b transcription. By experimentally assaying multiple enhancers in a variety of cell types, we show that regulation by H3K9me3 is a widely used mechanism which imparts specificity to the activities of otherwise broadly functional enhancers. Graphical abstract Graphical Abstract Highlights ► Enhancers of model inflammatory genes are regulated by neighboring H3K9me3 ► The demethylase JmjD2d regulates H3K9me3 levels around enhancers upon stimulation ► JmjD2d is required for cell-type-specific expression of a subset of NF-κB target genes ► 4H3K9me3 confers cell-type specificity on broadly functional enhancers throughout the genome
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