Chemical and psychological stressors can exert long lasting changes in brain function and behaviour. Changes in DNA methylation have been shown to be an important mechanism mediating long lasting changes in neural function and behaviour, especially for anxiety-like or stress responses. In the present study, we examined the effects of either a social or chemical stressor on DNA methyltransferase (DNMT) gene expression in the amygdala, an important brain region modulating stress responses and anxiety. In adult California mice (Peromyscus californicus) that were naïve to social defeat, females had higher levels of Dnmt1 expression in punch samples of the central amygdala (CeA) than males. In addition, mice that underwent social defeat stress showed reduced Dnmt1 and Dnmt3a expression in the CeA of females but not males. A second study using more anatomically specific punch samples replicated these effects for Dnmt1. Perinatal exposure (spanning from periconception through lactation) to bisphenol A or ethinyl oestradiol (oestrogens in birth control pills) also abolished sex differences in Dnmt1 expression in the CeA but not the basolateral amygdala. These findings identify a robust sex difference in Dnmt1 expression in the CeA that is sensitive to both psychological and chemical stressors. Future studies should aim to examine the impact of psychological and chemical stressors on DNA methylation in the CeA and also investigate whether Dnmt1 may have an underappreciated role in plasticity in behaviour.

The potential for implementation of HIV vaccine trials in hard-to-reach female sex workers in an inner city area of Barcelona, Spain was assessed via a study of HIV risk, willingness to participate and the success of retention strategies. In 130 women, ser

We show that the modulational instability growth rate of zonal flows is determined directly from the quasilinear wave kinetic equation. We also demonstrate the relation between zonal-flow growth and the cross bispectrum of the high-frequency drift-wave-driven Reynolds stress and the low-frequency plasma potential by explicit calculation. Experimental measurements of the spatiotemporal evolution of the spectrum integrated bicoherence at the L-->H transition near the edge shear layer indicate a modification in the nonlinear phase coupling, which might be linked to the generation of sheared ExB flows.

© 2014 Esteve-Puig et al.Exposure to ultraviolet (UV) radiation from sunlight accounts for 90% of the symptoms of premature skin aging and skin cancer. The tumor suppressor serine-threonine kinase LKB1 is mutated in Peutz-Jeghers syndrome and in a spectrum

Liver is a unique organ in displaying a reparative and regenerative response after acute/chronic damage or partial hepatectomy, when all the cell types must proliferate to re-establish the liver mass. The NADPH oxidase NOX4 mediates Transforming Growth Factor-beta (TGF-β) actions, including apoptosis in hepatocytes and activation of stellate cells to myofibroblasts. Aim of this work was to analyze the impact of NOX4 in liver regeneration by using two mouse models where Nox4 was deleted: 1) general deletion of Nox4 (NOX4-/-) and 2) hepatocyte-specific deletion of Nox4 (NOX4hepKO). Liver regeneration was analyzed after 2/3 partial hepatectomy (PH). Results indicated an earlier recovery of the liver-to-body weight ratio in both NOX4-/- and NOX4hepKO mice and an increased survival, when compared to corresponding WT mice. The regenerative hepatocellular fat accumulation and the parenchyma organization recovered faster in NOX4 deleted livers. Hepatocyte proliferation, analyzed by Ki67 and phospho-Histone3 immunohistochemistry, was accelerated and increased in NOX4 deleted mice, coincident with an earlier and increased Myc expression. Primary hepatocytes isolated from NOX4 deleted mice showed higher proliferative capacity and increased expression of Myc and different cyclins in response to serum. Transcriptomic analysis through RNA-seq revealed significant changes after PH in NOX4-/- mice and support a relevant role for Myc in a node of regulation of proliferation-related genes. Interestingly, RNA-seq also revealed changes in the expression of genes related to activation of the TGF-β pathway. In fact, levels of active TGF-β1, phosphorylation of Smads and levels of its target p21 were lower at 24 h in NOX4 deleted mice. Nox4 did not appear to be essential for the termination of liver regeneration in vivo, neither for the in vitro hepatocyte response to TGF-β1 in terms of growth inhibition, which suggest its potential as therapeutic target to improve liver regeneration, without adverse effects.

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model.

Accurate mock galaxy catalogues are crucial to validate analysis pipelines used to constrain dark energy models. We present a fast HOD-fitting method which we apply to the AbacusSummit simulations to create a set of mock catalogues for the DESI Bright Galaxy Survey, which contain r-band magnitudes and colours (g - r) The halo tabulation method fits HODs for different absolute magnitude threshold samples simultaneously, preventing unphysical HOD crossing between samples. We validate the HOD fitting procedure by fitting to real-space clustering measurements and galaxy number densities from the MXXL BGS mock, which was tuned to the SDSS and GAMA surveys. The best-fitting clustering measurements and number densities are mostly within the assumed errors, but the clustering for the faint samples is low on large scales. The best-fitting HOD parameters are robust when fitting to simulations with different realizations of the initial conditions. When varying the cosmology, trends are seen as a function of each cosmological parameter. We use the best-fitting HOD parameters to create cubic box and cut sky mocks from the AbacusSummit simulations, in a range of cosmologies. As an illustration, we compare the sample of galaxies in the mock with BGS measurements from the DESI one-percent survey. We find good agreement in the number densities, and the projected correlation function is reasonable, with differences that can be improved in the future by fitting directly to BGS clustering measurements. The cubic box and cut-sky mocks in different cosmologies are made publicly available.

Large-scale astronomical surveys have the potential to capture data on large numbers of strongly gravitationally lensed supernovae (LSNe). To facilitate timely analysis and spectroscopic follow-up before the supernova fades, an LSN needs to be identified soon after it begins. To quickly identify LSNe in optical survey data sets, we designed ZipperNet, a multibranch deep neural network that combines convolutional layers (traditionally used for images) with long short-term memory layers (traditionally used for time series). We tested ZipperNet on the task of classifying objects from four categories - no lens, galaxy-galaxy lens, lensed Type-Ia supernova, lensed core-collapse supernova - within high-fidelity simulations of three cosmic survey data sets: the Dark Energy Survey, Rubin Observatory's Legacy Survey of Space and Time (LSST), and a Dark Energy Spectroscopic Instrument (DESI) imaging survey. Among our results, we find that for the LSST-like data set, ZipperNet classifies LSNe with a receiver operating characteristic area under the curve of 0.97, predicts the spectroscopic type of the lensed supernovae with 79% accuracy, and demonstrates similarly high performance for LSNe 1-2 epochs after first detection. We anticipate that a model like ZipperNet, which simultaneously incorporates spatial and temporal information, can play a significant role in the rapid identification of lensed transient systems in cosmic survey experiments.

We present initial results from the Dark Energy Spectroscopic Instrument (DESI) complete calibration of the colour–redshift relation (DC3R2) secondary target survey. Our analysis uses 230 k galaxies that overlap with KiDS-VIKING ugriZYJHKs photometry to calibrate the colour–redshift relation and to inform photometric redshift (photo-z) inference methods of future weak lensing surveys. Together with emission line galaxies (ELGs), luminous red galaxies (LRGs), and the Bright Galaxy Survey (BGS) that provide samples of complementary colour, the DC3R2 targets help DESI to span 56 per cent of the colour space visible to Euclid and LSST with high confidence spectroscopic redshifts. The effects of spectroscopic completeness and quality are explored, as well as systematic uncertainties introduced with the use of common Self-Organizing Maps trained on different photometry than the analysis sample. We further examine the dependence of redshift on magnitude at fixed colour, important for the use of bright galaxy spectra to calibrate redshifts in a fainter photometric galaxy sample. We find that noise in the KiDS-VIKING photometry introduces a dominant, apparent magnitude dependence of redshift at fixed colour, which indicates a need for carefully chosen deep drilling fields, and survey simulation to model this effect for future weak lensing surveys.

Highly multiplexed, fiber-fed spectroscopy is enabling surveys of millions of stars and galaxies. The performance of these surveys depends on accurately positioning fibers in the focal plane to capture target light. We describe a technique to measure the positioning accuracy of fibers by dithering fibers slightly around their ideal locations. This approach also enables measurement of the total system throughput and point-spread function delivered to the focal plane. We then apply this technique to observations from the Dark Energy Survey Instrument (DESI), and demonstrate that DESI positions fibers to within 0.″08 of their targets (5% of a fiber diameter) and achieves a system throughput within about 7% of expectations.