Behrenshvidberg7895

An amendment to this paper has been published and can be accessed via a link at the top of the paper.Ventriculomegaly with cystic kidney disease (VMCKD) is a rare and severe disorder characterized by cerebral ventriculomegaly, greatly elevated maternal serum alpha-fetoprotein (MSAFP) or amniotic fluid alpha-fetoprotein (AFAFP) levels and kidney disease similar to Finnish congenital nephrosis. Recessive mutations in the CRB2 (NM_173689) gene have been shown to cause the syndrome. Here, we described a nonconsanguineous Chinese family with two fetuses affected with VMCKD. A novel compound heterozygous mutation was identified in the CRB2 gene with co-segregation. One mutation [c.1960G>C (p.A654P)] was inherited from the father, while another mutation [c.3078_c.3093delGGCGCGGCCCCGGCCC (p.L1026Lfs*110)] was inherited from the mother. Preimplantation genetic testing for monogenic disease (PGT-M) was performed for the carrier couple with full informed consent and successfully blocked the inheritance of the disease. Our study has important implications on molecular diagnosis and genetic counseling for VMCKD and extends the mutation spectrum in CRB2 gene.To define the relationship between the survival motor neuron 1 gene (SMN1) and SMN2, and explore the variability of these two genes within the generations, SMN1 and SMN2 copy numbers were determined for 227 SMA families. The association analysis indicated that there was a negative correlation between the copy number of SMN1 and SMN2 (Spearman = -0.472, P  less then  0.001) in 227 SMA children and 454 of their parents. The average SMN copies from father and mother in each SMA family were used to represent the copy number in the parent's generation. Subsequently, SMN transmission analysis showed that the similar distribution trend of SMN1 and SMN2 copy number was not only in the SMA children and their parents' generation but also in the non-SMA families. Moreover, when the SMN2 copy number was one in the parent's generation, 75% of their SMA children had type I and 25% of them had type II/III. However, when the SMN2 copies were three in the parent's generation, all of their SMA children were type II/III. Therefore, the diversity of SMN copies was mostly inherited and the SMN2 copy number in the parent's generation could predict the disease severity of SMA children to some extent.Hatching out from the zona pellucida (ZP) is a crucial step for blastocyst implantation and development. However, it is still unknown whether the location of the hatching site relative to the inner cell mass (ICM) affects embryo implantation and foetal development. Here, we classified hatching blastocysts into three categories, 0° ≤ θ ≤ 30°, 30°  less then  θ ≤ 60°, and 60°  less then  θ ≤ 90°, in which θ is determined based on the relative position of the hatching site to the arc midpoint of the ICM. Non-surgical embryo transfer (NSET) devices were employed to evaluate blastocyst implantation and embryo development. Of 1,827 hatching blastocysts, 43.84%, 30.60%, and 21.67% were categorized as 30°  less then  θ ≤ 60°, 0° ≤ θ ≤ 30°, and 60°  less then  θ ≤ 90°, respectively. Embryos with different hatching sites showed no distinct differences in blastocyst implantation; surrogate female pregnancy; embryo development to term; litter size, or offspring survival, gender, or body weight. Our results indicate that mouse blastocyst hatching site is not randomly distributed. Embryo implantation and development are not correlated with the blastocyst hatching site in mice. Thus, assessment of the blastocyst hatching site should not be recommended to evaluate mouse blastocyst implantation and developmental potential.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Idiopathic portal hypertension (IPH) mimics liver cirrhosis in many aspects, and no efficient imaging method to differentiate the two diseases has been reported to date. In this study, the imaging and pathological characteristics were analysed for both IPH and cirrhosis. From January 2015 to March 2019, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) images and pathological results from 16 IPH and 16 liver cirrhosis patients, as well as imaging results of 16 normal patients as a control group, were retrospectively reviewed. The age of the patients was 39 ± 20 years. There was a significant difference in the mean lumen diameter, wall thickness and ratio of thickness to diameter between the IPH and liver cirrhosis patients in the main and sagittal portal veins (P  less then  0.05), as well as in the lumen diameter and ratio of thickness to diameter between the IPH and liver cirrhosis patients in the Segment 3 (S3) portal vein (P  less then  0.05). In IPH patients, the main imaging changes were portal vein wall thickening, stenosis or occlusion, a low enhancement area along the portal vein in the delay phase in contrast-enhanced imaging, and a non-homogeneous change in T1WI. The corresponding pathological changes included interlobular vein thickening, stenosis, occlusion, portal area fibrosis, and atrophy or apoptosis of hepatocytes. The main imaging characteristic of liver cirrhosis was a nodular change in T1WI, and the related pathological change was pseudolobule formation. The imaging characteristics of IPH include thickening of the portal vein vascular wall, stenosis of the portal vein lumen and the absence of diffuse cirrhosis-like nodules. These imaging features have a definite pathological basis and could help make differential diagnoses between IPH and cirrhosis.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Impaired thermoregulation and lowered average daily gains (ADG) result when livestock graze toxic endophyte (Epichloë coenophialum)-infected tall fescue (E+) and are hallmark signs of fescue toxicosis (FT), a disease exacerbated by increased temperature and humidity (+temperature-humidity index; +THI). We previously reported FT is associated with metabolic and microbiota perturbations under thermoneutral conditions; here, we assessed the influence of E+ grazing and +THI on the microbiotametabolome interactions. Using high-resolution metabolomics and 16S rRNA gene sequencing, plasma/urine metabolomes and the fecal microbiota of Angus steers grazing non-toxic or E+ tall fescue were evaluated in the context of +THI. E+ grazing affected the fecal microbiota profile; +THI conditions modulated the microbiota only in E+ steers. E+ also perturbed many metabolic pathways, namely amino acid and inflammation-related metabolism; +THI affected these pathways only in E+ steers. Integrative analyses revealed the E+ microbiota correlated and co-varied with the metabolomes in a THI-dependent manner. selleck inhibitor Operational taxonomic units in the families Peptococcaceae, Clostridiaceae, and Ruminococcaceae correlated with production parameters (e.g., ADG) and with multiple plasma/urine metabolic features, providing putative FT biomarkers and/or targets for the development of FT therapeutics. Overall, this study suggests that E+ grazing increases Angus steer susceptibility to +THI, and offers possible targets for FT interventions.Minimal hepatic encephalopathy (MHE) is characterized by diffuse abnormalities in cerebral structure, such as reduced cortical thickness and altered brain parenchymal volume. This study tested the potential of gray matter (GM) volumetry to differentiate between cirrhotic patients with and without MHE using a support vector machine (SVM) learning method. High-resolution, T1-weighted magnetic resonance images were acquired from 24 cirrhotic patients with MHE and 29 cirrhotic patients without MHE (NHE). Voxel-based morphometry was conducted to evaluate the GM volume (GMV) for each subject. An SVM classifier was employed to explore the ability of the GMV measurement to diagnose MHE, and the leave-one-out cross-validation method was used to assess classification accuracy. The SVM algorithm based on GM volumetry achieved a classification accuracy of 83.02%, with a sensitivity of 83.33% and a specificity of 82.76%. The majority of the most discriminative GMVs were located in the bilateral frontal lobe, bilateral lentiform nucleus, bilateral thalamus, bilateral sensorimotor areas, bilateral visual regions, bilateral temporal lobe, bilateral cerebellum, left inferior parietal lobe, and right precuneus/posterior cingulate gyrus. Our results suggest that SVM analysis based on GM volumetry has the potential to help diagnose MHE in cirrhotic patients.Refractory functional dyspepsia (RFD) is characterized by symptoms persistence in spite of medical treatment or H. pylori eradication. No study has yet investigated the presence of gluten-dependent RFD as a clinical presentation of Non-Celiac Gluten Sensitivity (NCGS). Patients with RFD, in whom celiac disease, wheat allergy and H. pylori infection had been ruled out, followed a six weeks long gluten-free diet (GFD). Symptoms were evaluated by means of visual analogue scales; patients with ≥30% improvement in at least one of the reported symptoms after GFD underwent a double-blind placebo controlled gluten challenge. Subjects were randomly divided in two groups and symptoms were evaluated after the gluten/placebo challenge. GFD responders were further followed on for 3 months to evaluate the relationship between symptoms and gluten consumption. Out of 77 patients with RFD, 50 (65%) did not respond to GFD; 27 (35%) cases showed gastrointestinal symptoms improvement while on GFD; after blind gluten ingestion, symptoms recurred in 5 cases (6.4% of patients with RFD, 18% of GFD responders) suggesting the presence of NCGS. Furthermore, such extra-intestinal symptoms as fatigue and weakness (P = 0.000), musculo-skeletal pain (P = 0.000) and headache (P = 0.002) improved in NCGS patients on GFD. Because of the high prevalence of NCGS among patients with RFD, a diagnostic/therapeutic roadmap evaluating the effect of GFD in patients with RFD seems a reasonable (and simple) approach.An amendment to this paper has been published and can be accessed via a link at the top of the paper.During this paper, we improved the compressive strength of cementitious matrix based on ion exchanging resin (IER) at 12% and formulated by the modified novolac epoxy polymer surfactant (NEPS) at various percentages (0, 1, 2, 3, 4 and 5%). The results show that the introduction of 1% and 2% of NEPS in the cementitious matrix with 12% of IER increases the compressive strength compared to that of the basic matrix (from 7 to 90 days). However, the formulations 3, 4 and 5% show the compressive strength is less than that of the basic matrix (from 28 to 90 days).Kinases are involved in numerous critical cell signaling processes, and dysregulation in kinase signaling is implicated in many types of human cancers. In this study, we applied a parallel-reaction monitoring (PRM)-based targeted proteomic method to assess kinome reprogramming during melanoma metastasis in three pairs of matched primary/metastatic human melanoma cell lines. Around 300 kinases were detected in each pair of cell lines, and the results showed that Janus kinase 3 (JAK3) was with reduced expression in the metastatic lines of all three pairs of melanoma cells. Interrogation of The Cancer Genome Atlas (TCGA) data showed that reduced expression of JAK3 is correlated with poorer prognosis in melanoma patients. Additionally, metastatic human melanoma cells/tissues exhibited diminished levels of JAK3 mRNA relative to primary melanoma cells/tissues. Moreover, JAK3 suppresses the migration and invasion of cultured melanoma cells by modulating the activities of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9).