Detecting and Characterizing Mg ii Absorption in DESI Survey Validation Quasar Spectra

We present findings of the detection of Magnesium II (Mg ii, λ = 2796, 2803 Å) absorbers from the early data release of the Dark Energy Spectroscopic Instrument (DESI). DESI is projected to obtain spectroscopy of approximately 3 million quasars (QSOs), of which over 99% are anticipated to be at redshifts greater than z > 0.3, such that DESI would be able to observe an associated or intervening Mg ii absorber illuminated by the background QSO. We have developed an autonomous supplementary spectral pipeline that detects these systems through an initial line-fitting process and then confirms the line properties using a Markov Chain Monte Carlo sampler. Based upon a visual inspection of the resulting systems, we estimate that this sample has a purity greater than 99%. We have also investigated the completeness of our sample in regard to both the signal-to-noise properties of the input spectra and the rest-frame equivalent width (W 0) of the absorber systems. From a parent catalog containing 83,207 quasars, we detect a total of 23,921 Mg ii absorption systems following a series of quality cuts. Extrapolating from this occurrence rate of 28.8% implies a catalog at the completion of the five-year DESI survey that will contain over eight hundred thousand Mg ii absorbers. The cataloging of these systems will enable significant further research because they carry information regarding circumgalactic medium environments, the distribution of intervening galaxies, and the growth of metallicity across the redshift range 0.3 ≤ z < 2.5

T Cell-Dependence of Lassa Fever Pathogenesis

Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development

Performance of the Quasar Spectral Templates for the Dark Energy Spectroscopic Instrument

Millions of quasar spectra will be collected by the Dark Energy Spectroscopic Instrument (DESI), leading to a fourfold increase in the number of known quasars. High-accuracy quasar classification is essential to tighten constraints on cosmological parameters measured at the highest redshifts DESI observes (z > 2.0). We present spectral templates for identification and redshift estimation of quasars in the DESI Year 1 data release. The quasar templates are comprised of two quasar eigenspectra sets, trained on spectra from the Sloan Digital Sky Survey. The sets are specialized to reconstruct quasar spectral variation observed over separate yet overlapping redshift ranges and, together, are capable of identifying DESI quasars from 0.05 < z < 7.0. The new quasar templates show significant improvement over the previous DESI quasar templates regarding catastrophic failure rates, redshift precision and accuracy, quasar completeness, and the contamination fraction in the final quasar sample

Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure.

OBJECTIVE: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP). METHODS: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses. RESULTS: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction < 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSION: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings

The Interaction between the First Transmembrane Domain and the Thumb of ASIC1a Is Critical for Its N-Glycosylation and Trafficking

Acid-sensing ion channel-1a (ASIC1a), the primary proton receptor in the brain, contributes to multiple diseases including stroke, epilepsy and multiple sclerosis. Thus, a better understanding of its biogenesis will provide important insights into the regulation of ASIC1a in diseases. Interestingly, ASIC1a contains a large, yet well organized ectodomain, which suggests the hypothesis that correct formation of domain-domain interactions at the extracellular side is a key regulatory step for ASIC1a maturation and trafficking. We tested this hypothesis here by focusing on the interaction between the first transmembrane domain (TM1) and the thumb of ASIC1a, an interaction known to be critical in channel gating. We mutated Tyr71 and Trp287, two key residues involved in the TM1-thumb interaction in mouse ASIC1a, and found that both Y71G and W287G decreased synaptic targeting and surface expression of ASIC1a. These defects were likely due to altered folding; both mutants showed increased resistance to tryptic cleavage, suggesting a change in conformation. Moreover, both mutants lacked the maturation of N-linked glycans through mid to late Golgi. These data suggest that disrupting the interaction between TM1 and thumb alters ASIC1a folding, impedes its glycosylation and reduces its trafficking. Moreover, reducing the culture temperature, an approach commonly used to facilitate protein folding, increased ASIC1a glycosylation, surface expression, current density and slowed the rate of desensitization. These results suggest that correct folding of extracellular ectodomain plays a critical role in ASIC1a biogenesis and function

The Target-selection Pipeline for the Dark Energy Spectroscopic Instrument

In 2021 May, the Dark Energy Spectroscopic Instrument (DESI) began a 5 yr survey of approximately 50 million total extragalactic and Galactic targets. The primary DESI dark-time targets are emission line galaxies, luminous red galaxies, and quasars. In bright time, DESI will focus on two surveys known as the Bright Galaxy Survey and the Milky Way Survey. DESI also observes a selection of “secondary” targets for bespoke science goals. This paper gives an overview of the publicly available pipeline (desitarget) used to process targets for DESI observations. Highlights include details of the different DESI survey targeting phases, the targeting ID (TARGETID) used to define unique targets, the bitmasks used to indicate a particular type of target, the data model and structure of DESI targeting files, and examples of how to access and use the desitarget code base. This paper will also describe “supporting” DESI target classes, such as standard stars, sky locations, and random catalogs that mimic the angular selection function of DESI targets. The DESI target-selection pipeline is complex and sizable; this paper attempts to summarize the most salient information required to understand and work with DESI targeting data

Target Selection and Validation of DESI Quasars

The Dark Energy Spectroscopic Instrument (DESI) survey will measure large-scale structures using quasars as direct tracers of dark matter in the redshift range 0.9 2.1. We present several methods to select candidate quasars for DESI, using input photometric imaging in three optical bands (g, r, z) from the DESI Legacy Imaging Surveys and two infrared bands (W1, W2) from the Wide-field Infrared Survey Explorer. These methods were extensively tested during the Survey Validation of DESI. In this paper, we report on the results obtained with the different methods and present the selection we optimized for the DESI main survey. The final quasar target selection is based on a random forest algorithm and selects quasars in the magnitude range of 16.5 2.1), exceeding the project requirements by 20%. The redshift distribution of the selected quasars is in excellent agreement with quasar luminosity function predictions

Diabetic Kidney Disease in FVB/NJ Akita Mice: Temporal Pattern of Kidney Injury and Urinary Nephrin Excretion

Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process