Molecular details of a starch utilization pathway in the human gut symbiont Eubacterium rectale

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110609/1/mmi12859.pd

A luminosity distribution for kilonovae based on short gamma-ray burst afterglows

The combined detection of a gravitational-wave signal, kilonova, and short gamma-ray burst (sGRB) from GW170817 marked a scientific breakthrough in the field of multi-messenger astronomy. But even before GW170817, there have been a number of sGRBs with possible associated kilonova detections. In this work, we re-examine these "historical" sGRB afterglows with a combination of state-of-the-art afterglow and kilonova models. This allows us to include optical/near-infrared synchrotron emission produced by the sGRB as well as ultraviolet/optical/near-infrared emission powered by the radioactive decay of $r$-process elements (i.e., the kilonova). Fitting the lightcurves, we derive the velocity and the mass distribution as well as the composition of the ejected material. The posteriors on kilonova parameters obtained from the fit were turned into distributions for the peak magnitude of the kilonova emission in different bands and the time at which this peak occurs. From the sGRB with an associated kilonova, we found that the peak magnitude in H bands falls in the range [-16.2, -13.1] ($95\%$ of confidence) and occurs within $0.8-3.6\,\rm days$ after the sGRB prompt emission. In g band instead we obtain a peak magnitude in range [-16.8, -12.3] occurring within the first $18\,\rm hr$ after the sGRB prompt. From the luminosity distributions of GW170817/AT2017gfo, kilonova candidates GRB130603B, GRB050709 and GRB060614 (with the possible inclusion of GRB150101B) and the upper limits from all the other sGRBs not associated with any kilonova detection we obtain for the first time a kilonova luminosity function in different bands.Comment: Published in MNRAS, 24 pages, 14 figure

SusE facilitates starch uptake independent of starch binding in B. thetaiotaomicron

Black and white 8x10 acetate negativehttps://digitalmaine.com/arc_george_french_photos_f/1923/thumbnail.jp

A Cell-Surface GH9 Endo-Glucanase Coordinates with Surface Glycan Binding Proteins to Mediate Xyloglucan Uptake in the Gut Symbiont Bacteroides ovatus

Dietary fiber is an important food source for members of the human gut microbiome. Members of the dominant Bacteroidetes phylum capture diverse polysaccharides via the action of multiple cell surface proteins encoded within Polysaccharide Utilization Loci (PUL). The independent activities of PUL-encoded glycoside hydrolases (GH) and surface glycan-binding proteins (SGBPs) for the harvest of various glycans have been studied in detail, but how these proteins work together to coordinate uptake is poorly understood. Here, we combine genetic and biochemical approaches to discern the interplay between the BoGH9 endoglucanase and the xyloglucan-binding proteins SGBP-A and SGBP-B from the Bacteroides ovatus Xyloglucan Utilization Locus (XyGUL). The expression of BoGH9, a weakly active xyloglucanase in isolation, is required in a strain that expresses a non-binding version of SGBP-A (SGBP-A*). The crystal structure of the BoGH9 enzyme suggests the molecular basis for its robust activity on mixed-linkage β-glucan compared to xyloglucan. Yet, catalytically inactive site-directed mutants of BoGH9 fail to complement the deletion of the active BoGH9 in a SGBP-A* strain. We also find that SGBP-B is needed in an SGBP-A* background to support growth on xyloglucan, but that the non-binding SGBP-B* protein acts in a dominant negative manner to inhibit growth on xyloglucan. We postulate a model whereby the SGBP-A, SGBP-B and BoGH9 work together at the cell surface, likely within a discrete complex, and that xyloglucan binding by SGBP-B and BoGH9 may facilitate the orientation of the xyloglucan for transfer across the outer membrane

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

Ultracontinuous single haplotype genome assemblies for the domestic cat (Felis catus) and Asian leopard cat (Prionailurus bengalensis)

In addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. Previous diploid-based genome assemblies for the domestic cat have served as the primary reference for genomic studies within the cat family. However, these versions suffered from poor resolution of complex and highly repetitive regions, with substantial amounts of unplaced sequence that is polymorphic or copy number variable. We sequenced the genome of a female F1 Bengal hybrid cat, the offspring of a domestic cat (Felis catus) x Asian leopard cat (Prionailurus bengalensis) cross, with PacBio long sequence reads and used Illumina sequence reads from the parents to phase \u3e99.9% of the reads into the two species’ haplotypes. De novo assembly of the phased reads produced highly continuous haploid genome assemblies for the domestic cat and Asian leopard cat, with contig N50 statistics exceeding 83 Mb for both genomes. Whole genome alignments reveal the Felis and Prionailurus genomes are colinear, and the cytogenetic differences between the homologous F1 and E4 chromosomes represent a case of centromere repositioning in the absence of a chromosomal inversion. Both assemblies offer significant improvements over the previous domestic cat reference genome, with a 100% increase in contiguity and the capture of the vast majority of chromosome arms in one or two large contigs. We further demonstrated that comparably accurate F1 haplotype phasing can be achieved with members of the same species when one or both parents of the trio are not available. These novel genome resources will empower studies of feline precision medicine, adaptation and speciation

Lentivirus-mediated gene therapy for Fabry disease

Enzyme and chaperone therapies are used to treat Fabry disease. Such treatments are expensive and require intrusive biweekly infusions; they are also not particularly efficacious. In this pilot, single-arm study (NCT02800070), five adult males with Type 1 (classical) phenotype Fabry disease were infused with autologous lentivirus-transduced, CD34+-selected, hematopoietic stem/progenitor cells engineered to express alpha-galactosidase A (α-gal A). Safety and toxicity are the primary endpoints. The non-myeloablative preparative regimen consisted of intravenous melphalan. No serious adverse events (AEs) are attributable to the investigational product. All patients produced α-gal A to near normal levels within one week. Vector is detected in peripheral blood and bone marrow cells, plasma and leukocytes demonstrate α-gal A activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are seen. While the study and evaluations are still ongoing, the first patient is nearly three years post-infusion. Three patients have elected to discontinue enzyme therapy

A luminosity distribution for kilonovae based on short gamma-ray burst afterglows

The combined detection of a gravitational-wave signal, kilonova, and short gamma-ray burst (sGRB) from GW170817 marked a scientific breakthrough in the field of multimessenger astronomy. But even before GW170817, there have been a number of sGRBs with possible associated kilonova detections. In this work, we re-examine these ‘historical’ sGRB afterglows with a combination of state-of-the-art afterglow and kilonova models. This allows us to include optical/near-infrared synchrotron emission produced by the sGRB as well as ultraviolet/optical/near-infrared emission powered by the radioactive decay of r-process elements (i.e. the kilonova). Fitting the light curves, we derive the velocity and the mass distribution as well as the composition of the ejected material. The posteriors on kilonova parameters obtained from the fit were turned into distributions for the peak magnitude of the kilonova emission in different bands and the time at which this peak occurs. From the sGRB with an associated kilonova, we found that the peak magnitude in H bands falls in the range [−16.2, −13.1] (⁠95 per cent of confidence) and occurs within 0.8−3.6d after the sGRB prompt emission. In g band instead we obtain a peak magnitude in range [−16.8, −12.3] occurring within the first 18 h after the sGRB prompt. From the luminosity distributions of GW170817/AT2017gfo, kilonova candidates GRB130603B, GRB050709, and GRB060614 (with the possible inclusion of GRB150101B, GRB050724A, GRB061201, GRB080905A, GRB150424A, and GRB160821B) and the upper limits from all the other sGRBs not associated with any kilonova detection we obtain for the first time a kilonova luminosity distribution in different bands

Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice?

Background: Aluminium-containing phosphate binders have long been used for treatment of hyperphosphatemia in dialysis patients. Their safety became controversial in the early 1980's after reports of aluminium related neurological and bone disease began to appear. Available historical evidence however, suggests that neurological toxicity may have primarily been caused by excessive exposure to aluminium in dialysis fluid, rather than aluminium-containing oral phosphate binders. Limited evidence suggests that aluminium bone disease may also be on the decline in the era of aluminium removal from dialysis fluid, even with continued use of aluminium binders