Polymorphism in TGFB1 is associated with worse non-relapse mortality and overall survival after stem cell transplantation with unrelated donors.

Transforming growth factor beta-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiological and pathogenic processes. We have sequenced TGFB1 regulatory region and assigned allelic genotypes in a large cohort of hematopoietic stem cell transplantation patients and donors. In this study, we analyzed 522 unrelated donor-patient pairs and examined the combined effect of all the common polymorphisms in this genomic region. In univariate analysis, we found that patients carrying a specific allele, 'p001', showed significantly reduced overall survival (5-year overall survival 30.7% for p001/ p001 patients vs. 41.6% others; P=0.032) and increased non-relapse mortality (1-year nonrelapse mortality: 39.0% vs. 25.4%; P=0.039) after transplantation. In multivariate analysis, the presence of a p001/ p001 genotype in patients was confirmed as an independent factor for reduced overall survival [hazard ratio=1.53 (1.04-2.24); P=0.031], and increased non-relapse mortality [hazard ratio=1.73 (1.06-2.83); P=0.030]. In functional experiments we found a trend towards a higher percentage of surface transforming growth factor beta-1-positive regulatory T cells after activation when the cells had a p001 allele (P=0.07). Higher or lower production of transforming growth factor beta-1 in the inflammatory context of hematopoietic stem cell transplantation may influence the development of complications in these patients. Findings indicate that TGFB1 genotype could potentially be of use as a prognostic factor in hematopoietic stem cell transplantation risk assessment algorithms

The VLBA CANDELS GOODS-North survey. II -Wide-field source catalogue comparison between the VLBA, EVN, e -MERLIN, and VLA

\ua9 2024 The Author(s).Deep radio surveys of e xtragalactic le gac y fields trace a large range of spatial and brightness temperature sensitivity scales, and therefore have differing biases to radio-emitting physical components within galaxies. This is particularly true of radio surveys performed at ≤ 1 arcsec angular resolutions, and so robust comparisons are necessary to better understand the biases present in each survey. We present a multiresolution and multiwav elength analysis of the sources detected in a new Very Long Baseline Array (VLBA) survey of the Cosmic Assembly Near-IR Deep Extrag alactic Leg acy Survey Great Observatories Origins Deep Surv e y-North field. F or the 24 VLBA-selected sources described in Paper I, we augment the VLBA data with EVN data, and ~0.1-1 arcsec angular resolution data provided by Very Large Array (VLA) and enhanced-Multi Element Remotely Linked Interferometry Network. This sample includes new active galactic nuclei (AGN) detected in this field, thanks to a new source extraction technique that adopts priors from ancillary multiwavelength data. The high brightness temperatures of these sources ( TB ≥ 106 K) confirm AGN cores, that would often be missed or ambiguous in lower-resolution radio data of the same sources. Furthermore, only 15 sources are identified as \u27radiative\u27 AGN based on available X-ray and infrared constraints. By combining VLA and VLBA measurements, we find evidence that the majority of the extended radio emission is also AGN dominated, with only three sources with evidence for extended potentially star formation-dominated radio emission. We demonstrate the importance of wide-field multiresolution (arcsecond-milliarcsecond) co v erage of the faint radio source population, for a complete picture of the multiscale processes within these galaxies

The Underestimation Of Egocentric Distance: Evidence From Frontal Matching Tasks

There is controversy over the existence, nature, and cause of error in egocentric distance judgments. One proposal is that the systematic biases often found in explicit judgments of egocentric distance along the ground may be related to recently observed biases in the perceived declination of gaze (Durgin & Li, Attention, Perception, & Psychophysics, in press), To measure perceived egocentric distance nonverbally, observers in a field were asked to position themselves so that their distance from one of two experimenters was equal to the frontal distance between the experimenters. Observers placed themselves too far away, consistent with egocentric distance underestimation. A similar experiment was conducted with vertical frontal extents. Both experiments were replicated in panoramic virtual reality. Perceived egocentric distance was quantitatively consistent with angular bias in perceived gaze declination (1.5 gain). Finally, an exocentric distance-matching task was contrasted with a variant of the egocentric matching task. The egocentric matching data approximate a constant compression of perceived egocentric distance with a power function exponent of nearly 1; exocentric matches had an exponent of about 0.67. The divergent pattern between egocentric and exocentric matches suggests that they depend on different visual cues

Inhibition of activin/nodal signalling is necessary for pancreatic differentiation of human pluripotent stem cells

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Electrophysiological Heterogeneity of Fast-Spiking Interneurons: Chandelier versus Basket Cells

In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells (BCs), are generally thought to have the same "fast-spiking" phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat) and morphology (chandelier vs. basket). We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species. © 2013 Povysheva et al

Laboratory and Numerical Study of Saltwater Upconing in Fractured Coastal Aquifers

Supplementary Materials: The following are available online at https://www.mdpi.com/article/10.3390/w13233331/s1.Copyright: © 2021 by the authors. This study investigated the saltwater upconing mechanism in fractured coastal aquifers. Head-induced saline intrusion was initiated into three narrow sandbox aquifers containing individual horizontal discontinuities placed on different positions. Subsequently, using a peristaltic pump, freshwater was abstracted from the aquifers’ center, triggering saltwater upconing. Progressively larger pumping rates were applied until critical conditions, resulting in the wells’ salinization, were achieved. Advanced image analysis algorithms were utilized to recreate the saltwater concentration fields and quantify the extent of the saline wedges with a high accuracy. A numerical model was successfully employed to simulate the laboratory results and conduct a comprehensive sensitivity analysis, further expanding the findings of this investigation. The impact of the fractures’ length, permeability and position on the upconing mechanism was identified. It was established that the presence of high permeability discontinuities significantly affected aquifer hydrodynamics. The conclusions of this study could constitute a contribution towards the successful management of real-world fractured coastal aquifers.EPSRC Standard Research (Grant No. EP/R019258/1)

Local circuits targeting parvalbumin-containing interneurons in layer IV of rat barrel cortex

Interactions between inhibitory interneurons and excitatory spiny neurons and also other inhibitory cells represent fundamental network properties which cause the so-called thalamo-cortical response transformation and account for the well-known receptive field differences of cortical layer IV versus thalamic neurons. We investigated the currently largely unknown morphological basis of these interactions utilizing acute slice preparations of barrel cortex in P19-21 rats. Layer IV spiny (spiny stellate, star pyramidal and pyramidal) neurons or inhibitory (basket and bitufted) interneurons were electrophysiologically characterized and intracellularly biocytin-labeled. In the same slice, we stained parvalbumin-immunoreactive (PV-ir) interneurons as putative target cells after which the tissue was subjected to confocal image acquisition. Parallel experiments confirmed the existence of synaptic contacts in these types of connection by correlated light and electron microscopy. The axons of the filled neurons differentially targeted barrel PV-ir interneurons: (1) The relative number of all contacted PV-ir cells within the axonal sphere was 5–17% for spiny (n = 10), 32 and 58% for basket (n = 2) and 12 and 13% for bitufted (n = 2) cells. (2) The preferential subcellular site which was contacted on PV-ir target cells was somatic for four and dendritic for five spiny cells; for basket cells, there was a somatic and for bitufted cells a dendritic preference in each examined case. (3) The highest number of contacts on a single PV-ir cell was 9 (4 somatic and 5 dendritic) for spiny neurons, 15 (10 somatic and 5 dendritic) for basket cells and 4 (1 somatic and 3 dendritic) for bitufted cells. These patterns suggest a cell type-dependent communication within layer IV microcircuits in which PV-ir interneurons provide not only feed-forward but also feedback inhibition thus triggering the thalamo-cortical response transformation

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

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The SNAPSHOT study protocol : SNAcking, Physical activity, Self-regulation, and Heart rate Over Time

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