1,518 research outputs found
MicroRNAs regulate Ca2+ homeostasis in murine embryonic stem cells
MicroRNAs (miRNAs) are important regulators of embryonic stem cell (ESC) biology, and their study has identified key regulatory mechanisms. To find novel pathways regulated by miRNAs in ESCs, we undertook a bioinformatics analysis of gene pathways differently expressed in the absence of miRNAs due to the deletion of Dicer, which encodes an RNase that is essential for the synthesis of miRNAs. One pathway that stood out was Ca2+ signaling. Interestingly, we found that Dicer-/- ESCs had no difference in basal cytoplasmic Ca2+ levels but were hyperresponsive when Ca2+ import into the endoplasmic reticulum (ER) was blocked by thapsigargin. Remarkably, the increased Ca2+ response to thapsigargin in ESCs resulted in almost no increase in apoptosis and no differences in stress response pathways, despite the importance of miRNAs in the stress response of other cell types. The increased Ca2+ response in Dicer-/- ESCs was also observed during purinergic receptor activation, demonstrating a physiological role for the miRNA regulation of Ca2+ signaling pathways. In examining the mechanism of increased Ca2+ responsiveness to thapsigargin, neither store-operated Ca2+ entry nor Ca2+ clearance mechanisms from the cytoplasm appeared to be involved. Rather, it appeared to involve an increase in the expression of one isoform of the IP3 receptors (Itpr2). miRNA regulation of Itpr2 expression primarily appeared to be indirect, with transcriptional regulation playing a major role. Therefore, the miRNA regulation of Itpr2 expression offers a unique mechanism to regulate Ca2+ signaling pathways in the physiology of pluripotent stem cells
A five-year retrospective review of snakebite patients admitted to a tertiary university hospital in Malaysia
BACKGROUND
Although the majority of the snakebite cases in Malaysia are due to non-venomous snakes, venomous bites cause significant morbidity and mortality if treatment measures, especially ant-venom therapy, are delayed.
METHODS
To determine the demographic characteristics, we conducted a retrospective study on all snakebite patients admitted to the Emergency Department of Hospital Universiti Sains Malaysia (HUSM) from January 2006 to December 2010.
RESULTS
In the majority of the 260 cases that we found (138 cases or 52.9%), the snake species was unidentified. The most common venomous snakebites among the identified species were caused by cobras (52 cases or 20%). Cobra bites are significantly more likely to result in severe envenomation compared to non-cobra bites. Post hoc analysis also showed that cobra bite patients are significantly less likely to have complete recovery than non-cobra bite patients (48 cases, 75.0% vs. 53 cases, 94.6%; p = 0.003) and more likely to result in local gangrene (11 cases, 17.2% vs. 3 cases, 5.4%; p = 0.044).
CONCLUSION
Cobra bites are significantly more likely to result in severe envenomation needing anti-venom administration and more likely to result in local gangrene, and the patients are significantly less likely to have complete recovery than those with non-cobra bites
Beyond LLM in M-theory
The Lin, Lunin, Maldacena (LLM) ansatz in D = 11 supports two independent
Killing directions when a general Killing spinor ansatz is considered. Here we
show that these directions always commute, identify when the Killing spinors
are charged, and show that both their inner product and resulting geometry are
governed by two fundamental constants. In particular, setting one constant to
zero leads to AdS7 x S4, setting the other to zero gives AdS4 x S7, while flat
spacetime is recovered when both these constants are zero. Furthermore, when
the constants are equal, the spacetime is either LLM, or it corresponds to the
Kowalski-Glikman solution where the constants are simply the mass parameter.Comment: 1+30 pages, footnote adde
Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions
We report on a search for metastable positively and negatively charged states
of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864.
We have sampled approximately six billion 10% most central Au+Pb interactions
and have observed no strangelet states (baryon number A < 100 droplets of
strange quark matter). We thus set upper limits on the production of these
exotic states at the level of 1-6 x 10^{-8} per central collision. These limits
are the best and most model independent for this colliding system. We discuss
the implications of our results on strangelet production mechanisms, and also
on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover
memorial edition
Type IIA orientifold compactification on SU(2)-structure manifolds
We investigate the effective theory of type IIA string theory on
six-dimensional orientifold backgrounds with SU(2)-structure. We focus on the
case of orientifolds with O6-planes, for which we compute the bosonic effective
action in the supergravity approximation. For a generic SU(2)-structure
background, we find that the low-energy effective theory is a gauged N=2
supergravity where moduli in both vector and hypermultiplets are charged. Since
all these supergravities descend from a corresponding N=4 background, their
scalar target space is always a quotient of a SU(1,1)/U(1) x
SO(6,n)/SO(6)xSO(n) coset, and is therefore also very constrained.Comment: 31 pages; v2: local report number adde
Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs
The reference annotations made for a genome sequence provide the framework
for all subsequent analyses of the genome. Correct annotation is particularly
important when interpreting the results of RNA-seq experiments where short
sequence reads are mapped against the genome and assigned to genes according to
the annotation. Inconsistencies in annotations between the reference and the
experimental system can lead to incorrect interpretation of the effect on RNA
expression of an experimental treatment or mutation in the system under study.
Until recently, the genome-wide annotation of 3-prime untranslated regions
received less attention than coding regions and the delineation of intron/exon
boundaries. In this paper, data produced for samples in Human, Chicken and A.
thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing
technology from Helicos Biosciences which locates 3-prime polyadenylation sites
to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine
examples are illustrated where this combination of data allowed: (1) gene and
3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb);
(2) disentangling of gene expression in complex regions; (3) clearer
interpretation of small RNA expression and (4) identification of novel genes.
While the specific examples displayed here may become obsolete as genome
sequences and their annotations are refined, the principles laid out in this
paper will be of general use both to those annotating genomes and those seeking
to interpret existing publically available annotations in the context of their
own experimental dataComment: 44 pages, 9 figure
The genomic evolution of human prostate cancer.
Prostate cancers are highly prevalent in the developed world, with inheritable risk contributing appreciably to tumour development. Genomic heterogeneity within individual prostate glands and between patients derives predominantly from structural variants and copy-number aberrations. Subtypes of prostate cancers are being delineated through the increasing use of next-generation sequencing, but these subtypes are yet to be used to guide the prognosis or therapeutic strategy. Herein, we review our current knowledge of the mutational landscape of human prostate cancer, describing what is known of the common mutations underpinning its development. We evaluate recurrent prostate-specific mutations prior to discussing the mutational events that are shared both in prostate cancer and across multiple cancer types. From these data, we construct a putative overview of the genomic evolution of human prostate cancer
The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species
Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13Â kb
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Bioavailability in soils
The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr
Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening
There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK) that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets
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