Effects of sex chromosome dosage on corpus callosum morphology in supernumerary sex chromosome aneuploidies.

BackgroundSupernumerary sex chromosome aneuploidies (sSCA) are characterized by the presence of one or more additional sex chromosomes in an individual's karyotype; they affect around 1 in 400 individuals. Although there is high variability, each sSCA subtype has a characteristic set of cognitive and physical phenotypes. Here, we investigated the differences in the morphometry of the human corpus callosum (CC) between sex-matched controls 46,XY (N =99), 46,XX (N =93), and six unique sSCA karyotypes: 47,XYY (N =29), 47,XXY (N =58), 48,XXYY (N =20), 47,XXX (N =30), 48,XXXY (N =5), and 49,XXXXY (N =6).MethodsWe investigated CC morphometry using local and global area, local curvature of the CC boundary, and between-landmark distance analysis (BLDA). We hypothesized that CC morphometry would vary differentially along a proposed spectrum of Y:X chromosome ratio with supernumerary Y karyotypes having the largest CC areas and supernumerary X karyotypes having significantly smaller CC areas. To investigate this, we defined an sSCA spectrum based on a descending Y:X karyotype ratio: 47,XYY, 46,XY, 48,XXYY, 47,XXY, 48,XXXY, 49,XXXXY, 46,XX, 47,XXX. We similarly explored the effects of both X and Y chromosome numbers within sex. Results of shape-based metrics were analyzed using permutation tests consisting of 5,000 iterations.ResultsSeveral subregional areas, local curvature, and BLDs differed between groups. Moderate associations were found between area and curvature in relation to the spectrum and X and Y chromosome counts. BLD was strongly associated with X chromosome count in both male and female groups.ConclusionsOur results suggest that X- and Y-linked genes have differential effects on CC morphometry. To our knowledge, this is the first study to compare CC morphometry across these extremely rare groups

An optical fiber hydrogen sensor using a palladium-coated ball lens

A self-referenced optical fiber refractometer using a ball lens as a sensor head has been developed and characterized. A 350-μm ball lens created at the tip of a single mode fiber has been coated with a 40-nm optically thin layer of palladium that reacts with hydrogen to form a hydride, which has a lower reflectivity than pure palladium. Optical reflectance measurements from the tip of the ball lens were performed to determine the hydrogen response. The change in reflectivity is proportional to the hydrogen concentration in the range 0% to 1% hydrogen in air with a detection limit down to 10 ppm (1σ) in air. This technique offers a simple sensor head arrangement, with a larger sampling area (~40 times) than a typical single-mode fiber core. A statistical image analysis of a palladium film, with cracks created by accelerated failure, confirms that the anticipated sensor area for a ball lens sensor head has a more predictable reflectivity than that of a bare fiber core

Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man

Interferometric Observations of Explosive Variables: V838 Mon, Nova Aql 2005, and RS Oph

During the last two years we have used the Palomar Testbed Interferometer to observe several explosive variable stars, including V838 Monocerotis, V1663 Aquilae and recently RS Ophiuchi. We observed V838 Monocerotis approximately 34 months after its eruption, and were able to resolve the ejecta. Observations of V1663 Aql were obtained starting 9 days after peak brightness and continued for 10 days. We were able to resolve the milliarcsecond-scale emission and follow the expansion of the nova photosphere. When combined with radial-velocity information, these observations can be used to infer the distance to the nova. Finally we have resolved the recurrent nova RS Oph and can draw some preliminary conclusions regarding the emission morphology.Comment: 8 Pages, SPIE Astronomical Telescopes and Instrumentation 2006, Advances in Stellar Interferometery, 6268-16

Quantifying the Origin and Distribution of Intracluster Light in a Fornax-like Cluster

Using a cosmological $N$-body simulation, we investigate the origin and distribution of stars in the intracluster light (ICL) of a Fornax-like cluster. In a dark matter only simulation we identify a halo which, at $z=0$, has $M_200 \simeq 4.1 \times 10^{13}M_{sun}$ and $r_{200} = 700kpc$, and replace infalling subhalos with models that include spheroid and disc components. As they fall into the cluster, the stars in some of these galaxies are stripped from their hosts, and form the ICL. We consider the separate contributions to the ICL from stars which originate in the haloes and the discs of the galaxies. We find that disc ICL stars are more centrally concentrated than halo ICL stars. The majority of the disc ICL stars are associated with one initially disc-dominated galaxy that falls to the centre of the cluster and is heavily disrupted, producing part of the cD galaxy. At radial distances greater than 200kpc, well beyond the stellar envelope of the cD galaxy, stars formerly from the stellar haloes of galaxies dominate the ICL. Therefore at large distances, the ICL population is dominated by older stars.Comment: Paper published as MNRAS , 2017, 467, 4501 This version corrects a small typo in the authors fiel

Fatigue related impairments in oculomotor control are prevented by caffeine

Strenuous exercise can result in an inability of the central nervous system to drive skeletal muscle e ectively, a phenomenon known as central fatigue. The impact of central fatigue on the oculomotor system is currently unexplored. Fatigue that originates in the central nervous system may be related to perturbations in the synthesis and metabolism of several neurotransmitters. In this study we examine central fatigue in the oculomotor system after prolonged exercise. The involvement of central neurotransmission was explored by administering ca eine during exercise. Within a double- blind, randomized, repeated measures, crossover design, 11 cyclists consumed a placebo or ca eine solution during 180 min of stationary cycling. Saccadic eye movements were measured using infra-red oculography. Exercise decreased saccade velocity by 8% (placebo trial). This e ect was reversed by ca eine, whereby velocity was increased by 11% after exercise. A non oculomotor perceptual task (global motion processing) was una ected by exercise. The human oculomotor system is impaired by strenuous exercise of the locomotor system. Ca eine exerts a protective e ect on oculomotor control, which could be related to up-regulated central neurotransmission. In addition, cortical processes supporting global motion perception appear to be robust to fatigue

Anticoagulant rodenticides on our public and community lands: spatial distribution of exposure and poisoning of a rare forest carnivore.

Anticoagulant rodenticide (AR) poisoning has emerged as a significant concern for conservation and management of non-target wildlife. The purpose for these toxicants is to suppress pest populations in agricultural or urban settings. The potential of direct and indirect exposures and illicit use of ARs on public and community forest lands have recently raised concern for fishers (Martes pennanti), a candidate for listing under the federal Endangered Species Act in the Pacific states. In an investigation of threats to fisher population persistence in the two isolated California populations, we investigate the magnitude of this previously undocumented threat to fishers, we tested 58 carcasses for the presence and quantification of ARs, conducted spatial analysis of exposed fishers in an effort to identify potential point sources of AR, and identified fishers that died directly due to AR poisoning. We found 46 of 58 (79%) fishers exposed to an AR with 96% of those individuals having been exposed to one or more second-generation AR compounds. No spatial clustering of AR exposure was detected and the spatial distribution of exposure suggests that AR contamination is widespread within the fisher's range in California, which encompasses mostly public forest and park lands Additionally, we diagnosed four fisher deaths, including a lactating female, that were directly attributed to AR toxicosis and documented the first neonatal or milk transfer of an AR to an altricial fisher kit. These ARs, which some are acutely toxic, pose both a direct mortality or fitness risk to fishers, and a significant indirect risk to these isolated populations. Future research should be directed towards investigating risks to prey populations fishers are dependent on, exposure in other rare forest carnivores, and potential AR point sources such as illegal marijuana cultivation in the range of fishers on California public lands

Patterns of Natural and Human-Caused Mortality Factors of a Rare Forest Carnivore, the Fisher (Pekania pennanti) in California.

Wildlife populations of conservation concern are limited in distribution, population size and persistence by various factors, including mortality. The fisher (Pekania pennanti), a North American mid-sized carnivore whose range in the western Pacific United States has retracted considerably in the past century, was proposed for threatened status protection in late 2014 under the United States Endangered Species Act by the United States Fish and Wildlife Service in its West Coast Distinct Population Segment. We investigated mortality in 167 fishers from two genetically and geographically distinct sub-populations in California within this West Coast Distinct Population Segment using a combination of gross necropsy, histology, toxicology and molecular methods. Overall, predation (70%), natural disease (16%), toxicant poisoning (10%) and, less commonly, vehicular strike (2%) and other anthropogenic causes (2%) were causes of mortality observed. We documented both an increase in mortality to (57% increase) and exposure (6%) from pesticides in fishers in just the past three years, highlighting further that toxicants from marijuana cultivation still pose a threat. Additionally, exposure to multiple rodenticides significantly increased the likelihood of mortality from rodenticide poisoning. Poisoning was significantly more common in male than female fishers and was 7 times more likely than disease to kill males. Based on necropsy findings, suspected causes of mortality based on field evidence alone tended to underestimate the frequency of disease-related mortalities. This study is the first comprehensive investigation of mortality causes of fishers and provides essential information to assist in the conservation of this species

Variable expression and silencing of CRISPR-Cas9 targeted transgenes identifies the AAVS1 locus as not an entirely safe harbour

Background: Diseases such as hypertrophic cardiomyopathy (HCM) can lead to severe outcomes including sudden death. The generation of human induced pluripotent stem cell (hiPSC) reporter lines can be useful for disease modelling and drug screening by providing physiologically relevant in vitro models of disease. The AAVS1 locus is cited as a safe harbour that is permissive for stable transgene expression, and hence is favoured for creating gene targeted reporter lines. Methods: We generated hiPSC reporters using a plasmid-based CRISPR/Cas9 nickase strategy. The first intron of PPP1R12C, the AAVS1 locus, was targeted with constructs expressing a genetically encoded calcium indicator (R-GECO1.0) or HOXA9-T2A-mScarlet reporter under the control of a pCAG or inducible pTRE promoter, respectively. Transgene expression was compared between clones before, during and/or after directed differentiation to mesodermal lineages. Results: Successful targeting to AAVS1 was confirmed by PCR and sequencing. Of 24 hiPSC clones targeted with pCAG-R-GECO1.0, only 20 expressed the transgene and in these, the percentage of positive cells ranged from 0% to 99.5%. Differentiation of a subset of clones produced cardiomyocytes, wherein the percentage of cells positive for R-GECO1.0 ranged from 2.1% to 93.1%. In the highest expressing R-GECO1.0 clones, transgene silencing occurred during cardiomyocyte differentiation causing a decrease in expression from 98.93% to 1.3%. In HOXA9-T2A-mScarlet hiPSC reporter lines directed towards mesoderm lineages, doxycycline induced a peak in transgene expression after two days but this reduced by up to ten-thousand-fold over the next 8-10 days. Nevertheless, for R-GECO1.0 lines differentiated into cardiomyocytes, transgene expression was rescued by continuous puromycin drug selection, which allowed the Ca 2+ responses associated with HCM to be investigated in vitro using single cell analysis. Conclusions: Targeted knock-ins to AAVS1 can be used to create reporter lines but variability between clones and transgene silencing requires careful attention by researchers seeking robust reporter gene expression