Gene Structure Evolution of the Na+-Ca2+ Exchanger (NCX) Family

<p>Abstract</p> <p>Background</p> <p>The Na⁺-Ca²⁺exchanger (NCX) is an important regulator of cytosolic Ca²⁺levels. Many of its structural features are highly conserved across a wide range of species. Invertebrates have a single <it>NCX </it>gene, whereas vertebrate species have multiple <it>NCX </it>genes as a result of at least two duplication events. To examine the molecular evolution of <it>NCX </it>genes and understand the role of duplicated genes in the evolution of the vertebrate <it>NCX </it>gene family, we carried out phylogenetic analyses of <it>NCX </it>genes and compared <it>NCX </it>gene structures from sequenced genomes and individual clones.</p> <p>Results</p> <p>A single <it>NCX </it>in invertebrates and the protochordate <it>Ciona</it>, and the presence of at least four <it>NCX </it>genes in the genomes of teleosts, an amphibian, and a reptile suggest that a four member gene family arose in a basal vertebrate. Extensive examination of mammalian and avian genomes and synteny analysis argue that <it>NCX4 </it>may be lost in these lineages. Duplicates for <it>NCX1</it>, <it>NCX2</it>, and <it>NCX4 </it>were found in all sequenced teleost genomes. The presence of seven genes encoding <it>NCX </it>homologs may provide teleosts with the functional specialization analogous to the alternate splicing strategy seen with the three <it>NCX </it>mammalian homologs.</p> <p>Conclusion</p> <p>We have demonstrated that <it>NCX4 </it>is present in teleost, amphibian and reptilian species but has been secondarily and independently lost in mammals and birds. Comparative studies on conserved vertebrate homologs have provided a possible evolutionary route taken by gene duplicates subfunctionalization by minimizing homolog number.</p

Gas Clumping in the Outskirts of Galaxy Clusters, an Assessment of the Sensitivity of STAR-X

In the outskirts of galaxy clusters, entropy profiles measured from X-ray observations of the hot intracluster medium (ICM) drops off unexpectedly. One possible explanation for this effect is gas clumping, where pockets of cooler and denser structures within the ICM are present. Current observatories are unable to directly detect these hypothetical gas clumps. One of the science drivers of the proposed STAR-X observatory is to resolve these or similar structures. Its high spatial resolution, large effective area, and low instrumental background make STAR-X ideal for directly detecting and characterizing clumps and diffuse emission in cluster outskirts. The aim of this work is to simulate observations of clumping in clusters to determine how well STAR-X will be able to detect clumps, as well as what clumping properties reproduce observed entropy profiles. This is achieved by using yt, pyXSIM, SOXS, and other tools to inject ideally modeled clumps into three-dimensional models derived from actual clusters using their observed profiles from other X-ray missions. Radial temperature and surface brightness profiles are then extracted from mock observations using concentric annuli. We find that in simulated observations for STAR-X, a parameter space of clump properties exists where gas clumps can be successfully identified using wavdetect and masked, and are able to recover the true cluster profiles. This demonstrates that STAR-X could be capable of detecting substructure in the outskirts of nearby clusters and that the properties of both the outskirts and the clumps will be revealed.Comment: This is a pre-copyedited, author-produced PDF of an article accepted for publication in RAS Techniques and Instruments (RASTI) following peer review. The version of record is available online at: https://academic.oup.com/rasti/article/doi/10.1093/rasti/rzad042/725882

ARHGEF9 disease: Phenotype clarification and genotype-phenotype correlation.

ObjectiveWe aimed to generate a review and description of the phenotypic and genotypic spectra of ARHGEF9 mutations.MethodsPatients with mutations or chromosomal disruptions affecting ARHGEF9 were identified through our clinics and review of the literature. Detailed medical history and examination findings were obtained via a standardized questionnaire, or if this was not possible by reviewing the published phenotypic features.ResultsA total of 18 patients (including 5 females) were identified. Six had de novo, 5 had maternally inherited mutations, and 7 had chromosomal disruptions. All females had strongly skewed X-inactivation in favor of the abnormal X-chromosome. Symptoms presented in early childhood with delayed motor development alone or in combination with seizures. Intellectual disability was severe in most and moderate in patients with milder mutations. Males with severe intellectual disability had severe, often intractable, epilepsy and exhibited a particular facial dysmorphism. Patients with mutations in exon 9 affecting the protein's PH domain did not develop epilepsy.ConclusionsARHGEF9 encodes a crucial neuronal synaptic protein; loss of function of which results in severe intellectual disability, epilepsy, and a particular facial dysmorphism. Loss of only the protein's PH domain function is associated with the absence of epilepsy

Diagnostic accuracy of Doppler ultrasound technique of the penile arteries in correlation to selective arteriography

In 63% of 265 patients with erectile dysfunction a relevant arterial inflow disturbance was found by Doppler ultrasound examination. Correlation between Doppler and arteriography in 58 patients showed an accuracy of 95% in detecting penile arteries and an accuracy of 91% in discovering a pathological arterial pattern (arterial anomaly or arteriosclerotic obstruction). In 15 patients the arterial inflow was measured additionally by Doppler ultrasound technique after intracavernosal injection of vasoactive drugs (IIVD) (7.5 mg papaverine and 0.25 mg phentolamine). This technique proved to be more reliable than in the flaccid state and markedly facilitated localization and assessment of pathological changes of the cavernosal arteries

Analysis of five deep-sequenced trio-genomes of the Peninsular Malaysia Orang Asli and North Borneo populations

BackgroundRecent advances in genomic technologies have facilitated genome-wide investigation of human genetic variations. However, most efforts have focused on the major populations, yet trio genomes of indigenous populations from Southeast Asia have been under-investigated.ResultsWe analyzed the whole-genome deep sequencing data (30x) of five native trios from Peninsular Malaysia and North Borneo, and characterized the genomic variants, including single nucleotide variants (SNVs), small insertions and deletions (indels) and copy number variants (CNVs). We discovered approximately 6.9 million SNVs, 1.2 million indels, and 9000 CNVs in the 15 samples, of which 2.7% SNVs, 2.3% indels and 22% CNVs were novel, implying the insufficient coverage of population diversity in existing databases. We identified a higher proportion of novel variants in the Orang Asli (OA) samples, i.e., the indigenous people from Peninsular Malaysia, than that of the North Bornean (NB) samples, likely due to more complex demographic history and long-time isolation of the OA groups. We used the pedigree information to identify de novo variants and estimated the autosomal mutation rates to be 0.81x10(-8) - 1.33x10(-8), 1.0x10(-9) - 2.9x10(-9), and 0.001 per site per generation for SNVs, indels, and CNVs, respectively. The trio-genomes also allowed for haplotype phasing with high accuracy, which serves as references to the future genomic studies of OA and NB populations. In addition, high-frequency inherited CNVs specific to OA or NB were identified. One example is a 50-kb duplication in DEFA1B detected only in the Negrito trios, implying plausible effects on host defense against the exposure of diverse microbial in tropical rainforest environment of these hunter-gatherers. The CNVs shared between OA and NB groups were much fewer than those specific to each group. Nevertheless, we identified a 142-kb duplication in AMY1A in all the 15 samples, and this gene is associated with the high-starch diet. Moreover, novel insertions shared with archaic hominids were identified in our samples.ConclusionOur study presents a full catalogue of the genome variants of the native Malaysian populations, which is a complement of the genome diversity in Southeast Asians. It implies specific population history of the native inhabitants, and demonstrated the necessity of more genome sequencing efforts on the multi-ethnic native groups of Malaysia and Southeast Asia

Gemini Planet Imager Observational Calibrations VI: Photometric and Spectroscopic Calibration for the Integral Field Spectrograph

The Gemini Planet Imager (GPI) is a new facility instrument for the Gemini Observatory designed to provide direct detection and characterization of planets and debris disks around stars in the solar neighborhood. In addition to its extreme adaptive optics and corona graphic systems which give access to high angular resolution and high-contrast imaging capabilities, GPI contains an integral field spectrograph providing low resolution spectroscopy across five bands between 0.95 and 2.5 $\mu$m. This paper describes the sequence of processing steps required for the spectro-photometric calibration of GPI science data, and the necessary calibration files. Based on calibration observations of the white dwarf HD 8049B we estimate that the systematic error in spectra extracted from GPI observations is less than 5%. The flux ratio of the occulted star and fiducial satellite spots within coronagraphic GPI observations, required to estimate the magnitude difference between a target and any resolved companions, was measured in the $H$-band to be $\Delta m = 9.23\pm0.06$ in laboratory measurements and $\Delta m = 9.39\pm 0.11$ using on-sky observations. Laboratory measurements for the $Y$, $J$, $K1$ and $K2$ filters are also presented. The total throughput of GPI, Gemini South and the atmosphere of the Earth was also measured in each photometric passband, with a typical throughput in $H$-band of 18% in the non-coronagraphic mode, with some variation observed over the six-month period for which observations were available. We also report ongoing development and improvement of the data cube extraction algorithm.Comment: 15 pages, 6 figures. Proceedings of the SPIE, 9147-30

The Role of Stress in Understanding Differences in Sedentary Behavior in Hispanic/Latino Adults: Results from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study

Chronic stress and/or lifetime traumatic stress can create a self-reinforcing cycle of unhealthy behaviors, such as overeating and sedentary behavior, that can lead to further increases in stress. This study examined the relationship between stress and sedentary behavior in a sample of Hispanic/Latino adults (N = 4244) from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study