Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut ...environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher's exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19.
We present high-resolution ALMA Band 6 and 7 observations of the tidally disrupted protoplanetary disks of the RW Aurigae binary. Our observations reveal tidal streams in addition to the previously ...observed tidal arm around RW Aur A. The observed configuration of tidal streams surrounding RW Aur A and B is incompatible with a single star-disk tidal encounter, suggesting that the RW Aurigae system has undergone multiple flyby interactions. We also resolve the circumstellar disks around RW Aur A and B, with CO radii of 58 au and 38 au consistent with tidal truncation, and 2.5 times smaller dust emission radii. The disks appear misaligned by 12° or 57°. Using new photometric observations from the American Association of Variable Star Observers (AAVSO) and the All Sky Automated Survey for SuperNovae (ASAS-SN) archives, we have also identified an additional dimming event of the primary that began in late 2017 and is currently ongoing. With over a century of photometric observations, we are beginning to explore the same spatial scales as ALMA.
The yellow colour of durum wheat (Triticum turgidum L. var durum) semolina is due in part to the presence of carotenoid pigments found in the endosperm and is an important end-use quality trait. We ...hypothesized that variation in the genes coding for phytoene synthase (Psy), a critical enzyme in carotenoid biosynthesis, may partially explain the phenotypic variation in endosperm colour observed among durum cultivars. Using rice sequence information, primers were designed to PCR clone and sequence the Psy genes from Kofa (high colour) and W9262-260D3 (medium colour) durum cultivars. Sequencing confirmed the presence of four Psy genes in each parent, corresponding to a two member gene family designated as Psy1-1, Psy1-2 and Psy2-1 and Psy2-2. A genetic map was constructed using 155 F₁-derived doubled haploid lines from the cross W9262-260D3/Kofa with 194 simple sequence repeat and DArT® markers. Using Psy1-1 and Psy2-1 allele-specific markers and chromosome mapping, the Psy1 and Psy2 genes were located to the group 7 and 5 chromosomes, respectively. Four quantitative trait loci (QTL) underlying phenotypic variation in endosperm colour were identified on chromosomes 2A, 4B, 6B, and 7B. The Psy1-1 locus co-segregated with the 7B QTL, demonstrating an association of this gene with phenotypic variation for endosperm colour. This work is the first report of mapping Psy genes and supports the role of Psy1-1 in elevated levels of endosperm colour in durum wheat. This gene is a target for the further development of a molecular marker to enhance selection for endosperm colour in durum wheat breeding programs.
Severe losses attributable to pre-harvest sprouting (PHS) have been reported in Canada in recent years. The genetics of PHS resistance have been more extensively studied in hexaploid wheat and ...generally not using combinations of elite agronomic parents. The objective of our research was to understand the genetic nature of PHS resistance in an elite durum cross. A doubled haploid (DH) population and checks were phenotyped in replicated trials for grain yield and PHS traits over 3 years in western Canada. The response of intact spikes to sprouting conditions, sampled over two development time points, was measured in a rain simulation chamber. The DH population was genotyped with simple sequence repeat and Diversity Arrays Technology markers. Genotypes were a significant source of variation for grain yield and PHS resistance traits in each tested environment. Transgressive segregant DH genotypes were identified for grain yield and PHS resistance measurements. Low or no correlation was detected between grain yield and PHS, while correlation between PHS resistance measurements was moderate. The heritability of PHS resistance was moderate and higher than grain yield. Significant quantitative trait loci with small effect were detected on chromosomes 1A, 1B, 5B, 7A and 7B. Both parents contributed to the PHS resistance. Promising DH genotypes with high and stable grain yield as well as PHS resistance were identified, suggesting that grain yield and PHS can be improved simultaneously in elite genetic materials, and that these DH genotypes will be useful parental material for durum breeding programs.
Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia, and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic ...homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF) 19/15 protein and mRNA levels, and 7α‐hydroxy‐4‐cholesten‐3‐one. Terminal ileal farnesoid X receptor (FXR)‐mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole‐genome sequencing and ultra‐performance liquid chromatography tandem mass spectrometry were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary CA supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy because of elevated bile salt hydrolase‐producing Bacteroidetes. CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. Conclusion: The altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15‐mediated hepatic repression of hepatic bile acid synthesis, resulting in hypercholanemia.
To delineate the frequency, course, risk factors, and neuroanatomy of hemispatial neglect in a large stroke cohort.
One thousand two hundred eighty-one patients with acute stroke were enrolled in a ...multicenter trial of an anticoagulant. Presence and severity of neglect were assessed with the NIH Stroke Scale (NIHSS) neglect item, assessing tactile extinction and visuospatial neglect at entry, daily for 1 week, and at 3 months. Head CT scans were obtained on day 7, and infarct location and size were characterized.
Neglect was common at presentation, occurring in 43% of right brain-lesioned (RBL) patients and 20% of left brain-lesioned (LBL) patients (p < 0.001). At 3 months, neglect was present in 17% of RBL patients and in 5% of LBL patients (p < 0.001). In RBL patients, neglect was most frequently associated with lesions involving the (in descending order) temporal, parietal, frontal, occipital lobes, basal ganglia, and thalamus. Neglect was more common and persistent with cortical than with subcortical lesions. Increasing age was associated with increased risk of neglect in RBL patients, whereas gender and handedness did not significantly affect neglect frequency.
This series confirms that hemispatial neglect may occur with damage to several supratentorial structures but is most common and persistent with lesions of the right temporoparietal cortex. Increasing age is associated with neglect, particularly after right brain lesions. Gender and handedness do not exert a marked effect on the likelihood of the occurrence of neglect.
Congenital myasthenic syndromes are a heterogeneous group of inherited disorders that arise from impaired signal transmission at the neuromuscular synapse. They are characterized by fatigable muscle ...weakness. We performed whole-exome sequencing to determine the underlying defect in a group of individuals with an inherited limb-girdle pattern of myasthenic weakness. We identify DPAGT1 as a gene in which mutations cause a congenital myasthenic syndrome. We describe seven different mutations found in five individuals with DPAGT1 mutations. The affected individuals share a number of common clinical features, including involvement of proximal limb muscles, response to treatment with cholinesterase inhibitors and 3,4-diaminopyridine, and the presence of tubular aggregates in muscle biopsies. Analyses of motor endplates from two of the individuals demonstrate a severe reduction of endplate acetylcholine receptors. DPAGT1 is an essential enzyme catalyzing the first committed step of N-linked protein glycosylation. Our findings underscore the importance of N-linked protein glycosylation for proper functioning of the neuromuscular junction. Using the DPAGT1-specific inhibitor tunicamycin, we show that DPAGT1 is required for efficient glycosylation of acetylcholine-receptor subunits and for efficient export of acetylcholine receptors to the cell surface. We suggest that the primary pathogenic mechanism of DPAGT1 mutations is reduced levels of acetylcholine receptors at the endplate region. These individuals share clinical features similar to those of congenital myasthenic syndrome due to GFPT1 mutations, and their disorder might be part of a larger subgroup comprising the congenital myasthenic syndromes that result from defects in the N-linked glycosylation pathway and that manifest through impaired neuromuscular transmission.
Leaf rust (Puccinia triticina Eriks.), stripe rust (Puccinia striiformis f. tritici Eriks.) and stem rust (Puccinia graminis f. sp. tritici) cause major production losses in durum wheat (Triticum ...turgidum L. var. durum). The objective of this research was to identify and map leaf, stripe and stem rust resistance loci from the French cultivar Sachem and Canadian cultivar Strongfield. A doubled haploid population from Sachem/Strongfield and parents were phenotyped for seedling reaction to leaf rust races BBG/BN and BBG/BP and adult plant response was determined in three field rust nurseries near El Batan, Obregon and Toluca, Mexico. Stripe rust response was recorded in 2009 and 2011 nurseries near Toluca and near Njoro, Kenya in 2010. Response to stem rust was recorded in field nurseries near Njoro, Kenya, in 2010 and 2011. Sachem was resistant to leaf, stripe and stem rust. A major leaf rust quantitative trait locus (QTL) was identified on chromosome 7B at Xgwm146 in Sachem. In the same region on 7B, a stripe rust QTL was identified in Strongfield. Leaf and stripe rust QTL around DArT marker wPt3451 were identified on chromosome 1B. On chromosome 2B, a significant leaf rust QTL was detected conferred by Strongfield, and at the same QTL, a Yr gene derived from Sachem conferred resistance. Significant stem rust resistance QTL were detected on chromosome 4B. Consistent interactions among loci for resistance to each rust type across nurseries were detected, especially for leaf rust QTL on 7B. Sachem and Strongfield offer useful sources of rust resistance genes for durum rust breeding.
Preharvest sprouting reduces grain quality and lowers grade. Characterization of preharvest sprouting resistance is important in selection in breeding for transgressive segregation and understanding ...the genetics of the trait for identifying QTL. Methods of measuring dormancy and other factors contributing to preharvest sprouting resistance are varied. The objective of this study was to demonstrate the requirement of multiple methods of measurement over multiple durations of germination to maximize understanding of transgressive segregation and QTL for preharvest sprouting resistance within a segregating durum wheat population grown in multiple environments. Ninety-eight durum wheat (
Triticum turgidum
L. var.
durum
) recombinant inbred lines (RIL) from a cross of a minimally dormant line, Sentry, by a moderately dormant line, Kyle, and controls were grown in replicated field tests in 1996, 1997 and 1998 and in a growth chamber trial in 1998. Preharvest sprouting was measured from intact spikes as sprouting index or from hand threshed grain as germination index (GI), germination resistance (GR), and percent germination (PG). The threshed grain measures were evaluated using counts at 7, 14 and 21 days intervals from the start of germination. Correlations performed on the measure type and duration using lines within the RIL population showed some discontinuity across environments, type of measure and duration of measure, with counts at extended intervals for PG producing the lowest correlations. The number of transgressive segregant lines varied with environment, duration and type of measure. Different QTL were identified by different types of measures and duration of counts. GI calculated for 7, 14 and 21 days germination count intervals and GR calculated for 21 days identified a highly significant QTL on chromosome1A (
QPhsd
.
spa
.-
1A
.
1
). GR calculated for 7 days identified a highly significant QTL on 2A (
QPhsd
.
spa
.-
2A
.
1
) in two different environments, and GI calculated for 21 days and PG at 7 days identified the same highly significant QTL on chromosome 7B (
QPhsd
.
spa
.-
7B
.
1
). The results indicated that multiple measures and durations of measure intervals must be applied to results collected across different environments to maximize the identification of QTL and transgressive segregants of the population segregating for preharvest sprouting resistance.
Levels of the heavy metal cadmium (Cd) in food products are a food safety concern. Grain Cd is higher in durum (Triticum turgidum L. var. durum) than in common wheat, so reduction of Cd in durum ...grain is a priority of breeding programs. Previous research demonstrated that a single dominant gene, Cdu1, confers the low grain Cd phenotype, but the map location of the gene is not known. A doubled haploid population segregating for Cd concentration, developed from the cross of W9262-260D3 (a Kyle*2/Biodur inbred selection with low Cd uptake) and Kofa (high Cd uptake) and mapped with microsatellite markers, was used to locate Cdu1. Grain Cd concentration was determined by standard laboratory methods on field grain samples in 2000 and 2001. The Cd concentration segregated bimodally, allowing Cdu1 to be mapped qualitatively as well as quantitatively with quantitative trait locus analysis. The Cdu1 gene mapped to the long arm of chromosome 5B.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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