ASXL1 mutations are associated with distinct epigenomic alterations that lead to sensitivity to venetoclax and azacytidine.

The BCL2-inhibitor, Venetoclax (VEN), has shown significant anti-leukemic efficacy in combination with the DNMT-inhibitor, Azacytidine (AZA). To explore the mechanisms underlying the selective sensitivity of mutant leukemia cells to VEN and AZA, we used cell-based isogenic models containing a common leukemia-associated mutation in the epigenetic regulator ASXL1. KBM5 cells with CRISPR/Cas9-mediated correction of the ASXL1 mutation showed reduced leukemic growth, increased myeloid differentiation, and decreased HOXA and BCL2 gene expression in vitro compared to uncorrected KBM5 cells.

Quantifying ecospace utilization and ecosystem engineering during the early Phanerozoic-The role of bioturbation and bioerosion.

The Cambrian explosion (CE) and the great Ordovician biodiversification event (GOBE) are the two most important radiations in Paleozoic oceans. We quantify the role of bioturbation and bioerosion in ecospace utilization and ecosystem engineering using information from 1367 stratigraphic units. An increase in all diversity metrics is demonstrated for the Ediacaran-Cambrian transition, followed by a decrease in most values during the middle to late Cambrian, and by a more modest increase during the Ordovician.

Chasing Uptake: Super-Resolution Microscopy in Endocytosis and Phagocytosis.

Since their invention about two decades ago, super-resolution microscopes have become a method of choice in cell biology. Owing to a spatial resolution below 50 nm, smaller than the size of most organelles, and an order of magnitude better than the diffraction limit of conventional light microscopes, super-resolution microscopy is a powerful technique for resolving intracellular trafficking. In this review we discuss discoveries in endocytosis and phagocytosis that have been made possible by super-resolution microscopy - from uptake at the plasma membrane, endocytic coat formation, and cytoskeletal rearrangements to endosomal maturation.

Super-resolution Imaging of Structure, Molecular Composition, and Stability of Single Oligonucleotide Polyplexes.

The successful application of gene therapy relies on the development of safe and efficient delivery vectors. Cationic polymers such as cell-penetrating peptides (CPPs) can condense genetic material into nanoscale particles, called polyplexes, and induce cellular uptake. With respect to this point, several aspects of the nanoscale structure of polyplexes have remained elusive because of the difficulty in visualizing the molecular arrangement of the two components with nanometer resolution.

Mapping of compositional properties of coal using isometric log-ratio transformation and sequential Gaussian simulation - A comparative study for spatial ultimate analyses data.

Chemical properties of coal largely determine coal handling, processing, beneficiation methods, and design of coal-fired power plants. Furthermore, these properties impact coal strength, coal blending during mining, as well as coal's gas content, which is important for mining safety. In order for these processes and quantitative predictions to be successful, safer, and economically feasible, it is important to determine and map chemical properties of coals accurately in order to infer these properties prior to mining.

Membrane permeation of arginine-rich cell-penetrating peptides independent of transmembrane potential as a function of lipid composition and membrane fluidity.

Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration.

[Inappropriate medication use among Chilean older people].

Background: Inappropriate medication use in older people is an important source of adverse events and complications.

Aim: To determine the frequency of inappropriate medication use in the general population.

Material And Methods: As part of the 2010 Chilean National Health Survey, 1,048 persons aged 65 years or more were interviewed about medication use.

Decoupled evolution of soft and hard substrate communities during the Cambrian Explosion and Great Ordovician Biodiversification Event.

Contrasts between the Cambrian Explosion (CE) and the Great Ordovician Biodiversification Event (GOBE) have long been recognized. Whereas the vast majority of body plans were established as a result of the CE, taxonomic increases during the GOBE were manifested at lower taxonomic levels. Assessing changes of ichnodiversity and ichnodisparity as a result of these two evolutionary events may shed light on the dynamics of both radiations.

Stochastic reservoir simulation for the modeling of uncertainty in coal seam degasification.

Coal seam degasification improves coal mine safety by reducing the gas content of coal seams and also by generating added value as an energy source. Coal seam reservoir simulation is one of the most effective ways to help with these two main objectives. As in all modeling and simulation studies, how the reservoir is defined and whether observed productions can be predicted are important considerations.

Time-Lapse Analysis of Methane Quantity in the Mary Lee Group of Coal Seams Using Filter-Based Multiple-Point Geostatistical Simulation.

Coal seam degasification and its success are important for controlling methane, and thus for the health and safety of coal miners. During the course of degasification, properties of coal seams change. Thus, the changes in coal reservoir conditions and in-place gas content as well as methane emission potential into mines should be evaluated by examining time-dependent changes and the presence of major heterogeneities and geological discontinuities in the field.

Sequential Gaussian co-simulation of rate decline parameters of longwall gob gas ventholes.

Gob gas ventholes (GGVs) are used to control methane inflows into a longwall mining operation by capturing the gas within the overlying fractured strata before it enters the work environment. Using geostatistical co-simulation techniques, this paper maps the parameters of their rate decline behaviors across the study area, a longwall mine in the Northern Appalachian basin. Geostatistical gas-in-place (GIP) simulations were performed, using data from 64 exploration boreholes, and GIP data were mapped within the fractured zone of the study area.

Gas emissions, minerals, and tars associated with three coal fires, Powder River Basin, USA.

Ground-based surveys of three coal fires and airborne surveys of two of the fires were conducted near Sheridan, Wyoming. The fires occur in natural outcrops and in abandoned mines, all containing Paleocene-age subbituminous coals. Diffuse (carbon dioxide (CO(2)) only) and vent (CO(2), carbon monoxide (CO), methane, hydrogen sulfide (H(2)S), and elemental mercury) emission estimates were made for each of the fires.

Geostatistical modeling of the gas emission zone and its in-place gas content for Pittsburgh-seam mines using sequential Gaussian simulation.

Determination of the size of the gas emission zone, the locations of gas sources within, and especially the amount of gas retained in those zones is one of the most important steps for designing a successful methane control strategy and an efficient ventilation system in longwall coal mining. The formation of the gas emission zone and the potential amount of gas-in-place (GIP) that might be available for migration into a mine are factors of local geology and rock properties that usually show spatial variability in continuity and may also show geometric anisotropy. Geostatistical methods are used here for modeling and prediction of gas amounts and for assessing their associated uncertainty in gas emission zones of longwall mines for methane control.

[Prevalence of metabolic syndrome among Chilean adults].

Background: There are several diagnostic criteria for Metabolic Syndrome (MS) definition.

Aim: To study their application in the Chilean general adult population.

Material And Methods: We analyzed data from a random sub sample of 1.

Navajo coal combustion and respiratory health near Shiprock, New Mexico.

Indoor air pollution has been identified as a major risk factor for acute and chronic respiratory diseases throughout the world. In the sovereign Navajo Nation, an American Indian reservation located in the Four Corners area of the USA, people burn coal in their homes for heat. To explore whether/how indoor coal combustion might contribute to poor respiratory health of residents, this study examined respiratory health data, identified household risk factors such as fuel and stove type and use, analyzed samples of locally used coal, and measured and characterized fine particulate airborne matter inside selected homes.

The Einstein Center for Epigenomics: studying the role of epigenomic dysregulation in human disease.

There is increasing interest in the role of epigenetic and transcriptional dysregulation in the pathogenesis of a range of human diseases, not just in the best-studied example of cancer. It is, however, quite difficult for an individual investigator to perform these studies, as they involve genome-wide molecular assays combined with sophisticated computational analytical approaches of very large datasets that may be generated from various resources and technologies. In 2008, the Albert Einstein College of Medicine in New York, USA established a Center for Epigenomics to facilitate the research programs of its investigators, providing shared resources for genome-wide assays and for data analysis.

Recent results on the spatiotemporal modelling and comparative analysis of Black Death and bubonic plague epidemics.

Background: This work demonstrates the importance of spatiotemporal stochastic modelling in constructing maps of major epidemics from fragmentary information, assessing population impacts, searching for possible etiologies, and performing comparative analysis of epidemics.

Methods: Based on the theory previously published by the authors and incorporating new knowledge bases, informative maps of the composite space-time distributions were generated for important characteristics of two major epidemics: Black Death (14th century Western Europe) and bubonic plague (19th-20th century Indian subcontinent).

Results: The comparative spatiotemporal analysis of the epidemics led to a number of interesting findings: (1) the two epidemics exhibited certain differences in their spatiotemporal characteristics (correlation structures, trends, occurrence patterns and propagation speeds) that need to be explained by means of an interdisciplinary effort; (2) geographical epidemic indicators confirmed in a rigorous quantitative manner the partial findings of isolated reports and time series that Black Death mortality was two orders of magnitude higher than that of bubonic plague; (3) modern bubonic plague is a rural disease hitting harder the small villages in the countryside whereas Black Death was a devastating epidemic that indiscriminately attacked large urban centres and the countryside, and while the epidemic in India lasted uninterruptedly for five decades, in Western Europe it lasted three and a half years; (4) the epidemics had reverse areal extension features in response to annual seasonal variations.

Duration of urban mortality for the 14th-century Black Death epidemic.

The Black Death epidemic of 1347-1351 was one of the most serious catastrophes in human history, yet it continues to be imperfectly described because of the small and often uncertain amount of information recorded and preserved. Analysis of data from 53 cities, with 200 to 120,000 residents, shows a relationship between urban population at the beginning of the epidemic and duration of the epidemic, thus throwing some light on the characteristics of the pestilence. A further relevance of the finding is its utility for estimating and resolving contradictory information.

A marine dinoflagellate, Amphidinium eilatiensis n. sp., from the benthos of a mariculture sedimentation pond in Eilat, Israel.

A species of Amphidinium bloomed in a mariculture sedimentation pond that was used to grow bivalves near the Gulf of Eilat, Israel. Its overall length averaged 13 microm, the hypocone was 11 microm, and its width was 8 microm. It has a ventral ridge.

Hypotensive and vasorelaxant effects of ethanolic extract from Jatropha gossypiifolia L. in rats.

The present work was carried out to examine the hypotensive effects of ethanolic extract (EE) from Jatropha gossypiifolia L. The oral administration of EE (125 or 250 mg kg(-1) day(-1)) caused a significant and dose-dependent reduction of the systolic blood pressure. The concentration-response curves to norepinephrine (NE) or Ca(2+) were non-parallelly shifted to the right and the maximum contractile responses were concentration dependently depressed by EE (0.

Immunomodulatory properties of Alternanthera tenella Colla aqueous extracts in mice.

Plants from the genus Alternanthera are thought to possess antimicrobial and antiviral properties. In Brazilian folk medicine, the aqueous extract of A. tenella Colla is used for its anti-inflammatory activity.

Mismatch repair gene mutations in renal cell carcinoma.

We investigated the spectrum and genetic basis for mismatch repair (MMR) deficiency in renal cell carcinoma (RCC) by examining expression of four MMR genes important for hereditary and sporadic carcinogenesis. MMR deficiency was assessed using microsatellite instability (MSI) and genetic analyses of 25 cell lines derived from renal tumors. MMR gene alterations were detected using reverse transcription of RNA coupled with polymerase chain reaction (RT-PCR) and DNA sequencing.

Conserved charges for gravity with locally anti-de sitter asymptotics.

A new formula for the conserved charges in 3+1 gravity for spacetimes with local anti-de Sitter asymptotic geometry is proposed. It is shown that requiring the action to have an extremum for this class of asymptotia sets the boundary term that must be added to the Lagrangian as the Euler density with a fixed weight factor. The resulting action gives rise to the mass and angular momentum as Noether charges associated to the asymptotic Killing vectors without requiring specification of a reference background in order to have a convergent expression.

Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: a structural basis for specific adaptor/caspase interaction.

Direct recruitment and activation of caspase-9 by Apaf-1 through the homophilic CARD/CARD (Caspase Recruitment Domain) interaction is critical for the activation of caspases downstream of mitochondrial damage in apoptosis. Here we report the solution structure of the Apaf-1 CARD domain and its surface of interaction with caspase-9 CARD. Apaf-1 CARD consists of six tightly packed amphipathic alpha-helices and is topologically similar to the RAIDD CARD, with the exception of a kink observed in the middle of the N-terminal helix.