In November 2004, a regional climate change workshop was held in Guatemala with the goal of analyzing how climate extremes had changed in the region. Scientists from Central America and northern ...South America brought long‐term daily temperature and precipitation time series from meteorological stations in their countries to the workshop. After undergoing careful quality control procedures and a homogeneity assessment, the data were used to calculate a suite of climate change indices over the 1961–2003 period. Analysis of these indices reveals a general warming trend in the region. The occurrence of extreme warm maximum and minimum temperatures has increased while extremely cold temperature events have decreased. Precipitation indices, despite the large and expected spatial variability, indicate that although no significant increases in the total amount are found, rainfall events are intensifying and the contribution of wet and very wet days are enlarging. Temperature and precipitation indices were correlated with northern and equatorial Atlantic and Pacific Ocean sea surface temperatures. However, those indices having the largest significant trends (percentage of warm days, precipitation intensity, and contribution from very wet days) have low correlations to El Niño–Southern Oscillation. Additionally, precipitation indices show a higher correlation with tropical Atlantic sea surface temperatures.
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and can be separated into two subtypes based upon molecular features with similarities to germinal centre B-cells (GCB-like) or ...activated B-cells (ABC-like). Here we identify gain of 3q27.2 as being significantly associated with adverse outcome in DLBCL and linked with the ABC-like subtype. This lesion includes the BCL6 oncogene, but does not alter BCL6 transcript levels or target-gene repression. Separately, we identify expression of BCL6 in a subset of human haematopoietic stem/progenitor cells (HSPCs). We therefore hypothesize that BCL6 may act by 'hit-and-run' oncogenesis. We model this hit-and-run mechanism by transiently expressing Bcl6 within murine HSPCs, and find that it causes mature B-cell lymphomas that lack Bcl6 expression and target-gene repression, are transcriptionally similar to post-GCB cells, and show epigenetic changes that are conserved from HSPCs to mature B-cells. Together, these results suggest that BCL6 may function in a 'hit-and-run' role in lymphomagenesis.
Despite being frequently observed in cancer cells, chromosomal instability (CIN) and its immediate consequence, aneuploidy, trigger adverse effects on cellular homeostasis that need to be overcome by ...anti-stress mechanisms. As such, these safeguard responses represent a tumor-specific Achilles heel, since CIN and aneuploidy are rarely observed in normal cells. Recent data have revealed that epitranscriptomic marks catalyzed by RNA-modifying enzymes change under various stress insults. However, whether aneuploidy is associated with such RNA modifying pathways remains to be determined. Through an in silico search for aneuploidy biomarkers in cancer cells, we found TRMT61B, a mitochondrial RNA methyltransferase enzyme, to be associated with high levels of aneuploidy. Accordingly, TRMT61B protein levels are increased in tumor cell lines with an imbalanced karyotype as well as in different tumor types when compared to control tissues. Interestingly, while TRMT61B depletion induces senescence in melanoma cell lines with low levels of aneuploidy, it leads to apoptosis in cells with high levels. The therapeutic potential of these results was further validated by targeting TRMT61B in transwell and xenografts assays. We show that TRM61B depletion reduces the expression of several mitochondrial encoded proteins and limits mitochondrial function. Taken together, these results identify a new biomarker of aneuploidy in cancer cells that could potentially be used to selectively target highly aneuploid tumors.
We report on the first search for nuclear recoils from dark matter in the form of weakly interacting massive particles (WIMPs) with the XENONnT experiment, which is based on a two-phase time ...projection chamber with a sensitive liquid xenon mass of 5.9 ton. During the (1.09±0.03) ton yr exposure used for this search, the intrinsic ^{85}Kr and ^{222}Rn concentrations in the liquid target are reduced to unprecedentedly low levels, giving an electronic recoil background rate of (15.8±1.3) events/ton yr keV in the region of interest. A blind analysis of nuclear recoil events with energies between 3.3 and 60.5 keV finds no significant excess. This leads to a minimum upper limit on the spin-independent WIMP-nucleon cross section of 2.58×10^{-47} cm^{2} for a WIMP mass of 28 GeV/c^{2} at 90% confidence level. Limits for spin-dependent interactions are also provided. Both the limit and the sensitivity for the full range of WIMP masses analyzed here improve on previous results obtained with the XENON1T experiment for the same exposure.
Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE), characterized by abnormal B cell activation and differentiation to memory or plasma effector ...cells. However, the role of these cells in the pathogenesis of LN is not fully understood, as well as the effect of induction therapy on B cell subsets, possibly associated with this manifestation, like aged-associated B cells (ABCs). Consequently, we analyzed the molecules defining the ABCs subpopulation (CD11c, T-bet, and CD21) through flow cytometry of blood samples from patients with lupus presenting or not LN, following up a small sub-cohort after six months of induction therapy. The frequency of ABCs resulted higher in LN patients compared to healthy subjects. Unexpectedly, we identified a robust reduction of a CD21
hi
subset that was almost specific to LN patients. Moreover, several clinical and laboratory lupus features showed strong and significant correlations with this undefined B cell subpopulation. Finally, it was observed that the induction therapy affected not only the frequencies of ABCs and CD21
hi
subsets but also the phenotype of the CD21
hi
subset that expressed a higher density of CXCR5. Collectively, our results suggest that ABCs, and more importantly the CD21
hi
subset, may work to assess therapeutic response since the reduced frequency of CD21
hi
cells could be associated with the onset of LN.
Catheter-related bloodstream infections (CRBSI) constitute an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. The aim of these guidelines is to provide ...updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Experts in the field were designated by the two participating Societies (the Spanish Society of Infectious Diseases and Clinical Microbiology and SEIMC and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units SEMICYUC). Short-term peripheral venous catheters, non-tunneled and long-term central venous catheters, tunneled catheters and hemodialysis catheters are covered by these guidelines. The panel identified 39 key topics that were formulated in accordance with the PICO format. The strength of the recommendations and quality of the evidence were graded in accordance with ESCMID guidelines. Recommendations are made for the diagnosis of CRBSI with and without catheter removal and of tunnel infection. The document establishes the clinical situations in which a conservative diagnosis of CRBSI (diagnosis without catheter removal) is feasible. Recommendations are also made regarding empirical therapy, pathogen-specific treatment (coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus spp., Gram-negative bacilli, and Candida spp.), antibiotic lock therapy, diagnosis and management of suppurative thrombophlebitis and local complications.
Charged-current ν_{μ} interactions on carbon, iron, and lead with a final state hadronic system of one or more protons with zero mesons are used to investigate the influence of the nuclear ...environment on quasielasticlike interactions. The transferred four-momentum squared to the target nucleus, Q^{2}, is reconstructed based on the kinematics of the leading proton, and differential cross sections versus Q^{2} and the cross-section ratios of iron, lead, and carbon to scintillator are measured for the first time in a single experiment. The measurements show a dependence on the atomic number. While the quasielasticlike scattering on carbon is compatible with predictions, the trends exhibited by scattering on iron and lead favor a prediction with intranuclear rescattering of hadrons accounted for by a conventional particle cascade treatment. These measurements help discriminate between different models of both initial state nucleons and final state interactions used in the neutrino oscillation experiments.
Nanostructured composites of the aluminum 7075 alloy and carbon-coated silver nanoparticles were synthetized by the mechanical milling technique using a high-energy mill SPEX8000M; the powders ...generated were compacted, sintered and hot-extruded to produce 1 cm-diameter bars. The composites were then subjected to a wear test using a pin-on-disc device to validate the hypothesis that second phase-ductile nanometric particles homogenously distributed throughout the metal-matrix improve the wear resistance of the material. It was found that silver nanoparticles prevent the wear of the material by acting as an obstacle to dislocations movement during the plastic deformation of the contact surface, as well as a solid lubricant when these are separated from the metal-matrix.
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