Enhanced cerebral blood volume under normobaric hyperoxia in the J20-hAPP mouse model of Alzheimer’s disease

Early impairments to neurovascular coupling have been proposed to be a key pathogenic factor in the onset and progression of Alzheimer’s disease (AD). Studies have shown impaired neurovascular function in several mouse models of AD, including the J20-hAPP mouse. In this study, we aimed to investigate early neurovascular changes using wild-type (WT) controls and J20-hAPP mice at 6 months of age, by measuring cerebral haemodynamics and neural activity to physiological sensory stimulations. A thinned cranial window was prepared to allow access to cortical vasculature and imaged using 2D-optical imaging spectroscopy (2D-OIS). After chronic imaging sessions where the skull was intact, a terminal acute imaging session was performed where an electrode was inserted into the brain to record simultaneous neural activity. We found that cerebral haemodynamic changes were significantly enhanced in J20-hAPP mice compared with controls in response to physiological stimulations, potentially due to the significantly higher neural activity (hyperexcitability) seen in the J20-hAPP mice. Thus, neurovascular coupling remained preserved under a chronic imaging preparation. Further, under hyperoxia, the baseline blood volume and saturation of all vascular compartments in the brains of J20-hAPP mice were substantially enhanced compared to WT controls, but this effect disappeared under normoxic conditions. This study highlights novel findings not previously seen in the J20-hAPP mouse model, and may point towards a potential therapeutic strategy

Revealing Nanoscale Chemical Heterogeneities in Polycrystalline Mo-BiVO4 Thin Films

Indexación: Scopus.The activity of polycrystalline thin film photoelectrodes is impacted by local variations of the material properties due to the exposure of different crystal facets and the presence of grain/domain boundaries. Here a multi-modal approach is applied to correlate nanoscale heterogeneities in chemical composition and electronic structure with nanoscale morphology in polycrystalline Mo-BiVO4. By using scanning transmission X-ray microscopy, the characteristic structure of polycrystalline film is used to disentangle the different X-ray absorption spectra corresponding to grain centers and grain boundaries. Comparing both spectra reveals phase segregation of V2O5 at grain boundaries of Mo-BiVO4 thin films, which is further supported by X-ray photoelectron spectroscopy and many-body density functional theory calculations. Theoretical calculations also enable to predict the X-ray absorption spectral fingerprint of polarons in Mo-BiVO4. After photo-electrochemical operation, the degraded Mo-BiVO4 films show similar grain center and grain boundary spectra indicating V2O5 dissolution in the course of the reaction. Overall, these findings provide valuable insights into the degradation mechanism and the impact of material heterogeneities on the material performance and stability of polycrystalline photoelectrodes. © 2020 The Authors. Published by Wiley-VCH GmbHhttps://onlinelibrary-wiley-com.recursosbiblioteca.unab.cl/doi/10.1002/smll.20200160

Meditation-induced bliss viewed as release from conditioned neural (thought) patterns that block reward signals in the brain pleasure center

The nucleus accumbens orchestrates processes related to reward and pleasure, including the addictive consequences of repeated reward (e.g., drug addiction and compulsive gambling) and the accompanying feelings of craving and anhedonia. The neurotransmitters dopamine and endogenous opiates play interactive roles in these processes. They are released by natural rewards (i.e., food, water, sex, money, play, etc.) and are released or mimicked by drugs of abuse. Repeated drug use induces conditioned down-regulation of these neurotransmitters, thus causing painful suppression of everyday pleasure. As with many spiritual traditions, Buddhism provides strong advice against the pursuit of worldly pleasures to attain the ‘‘good life.’’ In contrast, many forms of meditation give rise to an immense and abiding joy. Most of these practices involve ‘‘stilling the mind,’’ whereby all content-laden thought (e.g., fantasies, daydreams, plans) ceases, and the mind enters a state of openness, formlessness, clarity, and bliss. This can be explained by the Buddhist suggestion that almost all of our everyday thoughts are a form of addiction. It follows that if we turn off this internal ‘‘gossip of ego,’’ we will find relief from the biochemical dopamine/opiate down-regulation, which is, perhaps, the perpetual concomitant of our daily rumination

An assessment of animal welfare impacts in wild Norway rat (Rattus norvegicus) management

Norway rats (Rattus norvegicus) are considered one of the most significant vertebrate pests globally, because of their impacts on human and animal health. There are legal and moral obligations to minimise the impacts of wildlife management on animal welfare, yet there are few data on the relative welfare impacts of rat trapping and baiting methods used in the UK with which to inform management decisions. Two stakeholder workshops were facilitated to assess the relative welfare impacts of six lethal rat management methods using a welfare assessment model. Fifteen stakeholders including experts in wildlife management, rodent management, rodent biology, animal welfare science, and veterinary science and medicine, participated. The greatest welfare impacts were associated with three baiting methods, anticoagulants, cholecalciferol and non-toxic cellulose baits (severe to extreme impact for days), and with capture on a glue trap (extreme for hours) with concussive killing (mild to moderate for seconds to minutes); these methods should be considered last resorts from a welfare perspective. Lower impacts were associated with cage trapping (moderate to severe for hours) with concussive killing (moderate for minutes). The impact of snap trapping was highly variable (no impact to extreme for seconds to minutes). Snap traps should be regulated and tested to identify those that cause rapid unconsciousness; such traps might represent the most welfare-friendly option assessed for killing rats. Our results can be used to integrate consideration of rat welfare alongside other factors, including cost, efficacy, safety, non-target animal welfare and public acceptability when selecting management methods. We also highlight ways of reducing welfare impacts and areas where more data are needed

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Topographic, spectral and thermal inertia analysis of interior layered deposits in Iani Chaos, Mars

We present an analysis of Interior Layered Deposits (ILDs) in Iani Chaos using visible, infrared, hyperspectral and topographic datasets acquired by instruments aboard NASA’s Mars Global Surveyor, Mars Odyssey, Mars Reconnaissance Orbiter and ESA’s Mars Express spacecraft. We focus on four main regions where ILDs outcrop in Iani Chaos. Deposits span a ∼2 km range of elevations and exhibit moderate to high albedos, layering at sub-decameter scales, thermal inertias of 300–800 J m−2 K−1 s−1/2 and a range of surface textures. Thermal inertia calculations use slope and azimuth corrections from High Resolution Stereo Camera (HRSC) topography. Spectral features in hyperspectral data acquired by NASA’s Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) suggest that gypsum (CaSO4·2H2O) and kieserite (MgSO4·H2O) are present in most deposits. We report absorptions typically exhibited by alunite (KAl3(SO4)2(OH)6) and jarosite View the MathML sourceKFe33+(OH)6(SO4)2 as well as a number of features that may be attributable to a wide range of mono- and polyhydrated sulphates and hydroxyl-sulphates bearing a number of cations, including Mg2+, Fe2+, Fe3+ and Ca2+. Spectral features similar to those of ammonium sulphates may also be present. Analysis of a HiRISE stereo DEM shows planar layering in some ILDs, favouring a sedimentary deposition origin. Stratigraphic mapping of hydration and sulphate spectral features in flat ILDs in central Iani Chaos suggest that specific elevation intervals in the stratigraphic column were subject to different levels of hydration, perhaps during episodes of water table elevation. This is consistent with formation models for ILDs and hydrological modelling. Geomorphic characteristics of deposits in northern and southern Iani Chaos suggest their relatively recent exhumation and significant erosion by aeolian processes. We conclude that any formation theory for ILDs in Iani Chaos should support mechanisms for different hydration states at different stratigraphic elevations and subsequent significant aeolian erosion, burial and re-exposure

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development