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Affiliation involving dysbindin phrase using customized postoperative analysis as well as chemotherapy advantage amid patients along with gastric adenocarcinoma.
BACKGROUND Anti-Mi-2 antibody is a type of myositis-specific autoantibody found in idiopathic inflammatory myopathy patients. OBJECTIVES To investigate the clinical features and long-term outcomes in anti-Mi-2-positive dermatomyositis (DM) patients. MATERIALS AND METHODS Serum anti-Mi-2β antibodies were detected in 357 DM patients by enzyme-linked immunosorbent assays, and possible associated clinical features were investigated based on cross-sectional and longitudinal studies. RESULTS Of the DM patients, 40/357 (11.2%) were positive for anti-Mi-2β antibodies and found to have a significantly higher frequency of V sign (72.5% vs 45.7%; p = 0.001), shawl sign (60.0% vs 35.6%; p = 0.003), and muscle weakness (77.5% vs 57.1%; p = 0.013), but a lower incidence of interstitial lung disease (ILD) (37.5% vs 60.9%; p = 0.005) and malignancy (0% vs 12.0%; p = 0.041) than anti-Mi-2β-negative patients. Anti-Mi-2β antibody levels positively correlated with disease activity. After a median follow-up period of 44 months, 97.0% of patients showed clinical remission. Twenty-six anti-Mi-2β-positive patients had a disease course longer than two years, and 16/26 (61.5%) were monocyclic without relapse. Moreover, five patients (15.1%) were drug-free with complete remission for more than three months. Kaplan-Meier survival curves showed that DM patients with positive anti-Mi-2β had a significantly lower mortality rate compared to anti-Mi-2β-negative patients (log-rank; p = 0.035). Interestingly, anti-Mi-2β antibodies did not disappear in all patients over time. CONCLUSION Anti-Mi-2β antibodies were associated with a subgroup of DM with a low frequency of ILD and malignancy, good treatment response, and favourable outcome. Moreover, anti-Mi-2β levels correlated with disease activity.The development of a polarized neuron relies on the selective transport of proteins to axons and dendrites. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is poorly understood. Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubule-associated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cortex. TTI 101 price This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals. © 2020, He et al.A gene associated with Parkinson's disease regulates mitochondrial homeostasis, thus affecting innate immunity. © 2020, Wallings et al.Human patients carrying PAPP-A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-proliferation transition. Ionocytes, which are normally quiescent, re-enter the cell cycle under low [Ca2+] stress. Genetic deletion of Papp-aa, but not the closely related Papp-ab, abolished ionocyte proliferation and reduced calcified bone mass. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-Akt-Tor signaling in ionocytes. Under low Ca2+ stress, Papp-aa cleaved Igfbp5a. Under normal conditions, however, Papp-aa proteinase activity was suppressed and IGFs were sequestered in the IGF/Igfbp complex. Pharmacological disruption of the IGF/Igfbp complex or adding free IGF1 activated IGF signaling and promoted ionocyte proliferation. These findings suggest that Papp-aa-mediated local Igfbp5a cleavage functions as a [Ca2+]-regulated molecular switch linking IGF signaling to bone calcification by stimulating epithelial cell quiescence-proliferation transition under low Ca2+ stress. © 2020, Liu et al.Malaria remains at the forefront of scientific research and global political and funding agendas. link2 Malaria models have consistently oversimplified how mass interventions are implemented. Here, we present an individual based, spatially explicit model of P. falciparum malaria transmission that includes all the programmatic implementation details of mass drug administration (MDA) campaigns. We uncover how the impact of MDA campaigns is determined by the interaction between implementation logistics, patterns of human mobility and how transmission risk is distributed over space. Our results indicate that malaria elimination is only realistically achievable in settings with very low prevalence and can be hindered by spatial heterogeneities in risk. In highly mobile populations, accelerating MDA implementation increases likelihood of elimination; if populations are more static, deploying less teams would be cost optimal. We conclude that mass drug interventions can be an invaluable tool towards malaria elimination in low endemicity areas, specifically when paired with effective vector control. © 2020, Gao et al.The genus Lactobacillus comprises 261 species (at March 2020) that are extremely diverse at phenotypic, ecological and genotypic levels. This study evaluated the taxonomy of Lactobacillaceae and Leuconostocaceae on the basis of whole genome sequences. Parameters that were evaluated included core genome phylogeny, (conserved) pairwise average amino acid identity, clade-specific signature genes, physiological criteria and the ecology of the organisms. Based on this polyphasic approach, we propose reclassification of the genus Lactobacillus into 25 genera including the emended genus Lactobacillus, which includes host-adapted organisms that have been referred to as the Lactobacillus delbrueckii group, Paralactobacillus and 23 novel genera for which the names Holzapfelia, Amylolactobacillus, Bombilactobacillus, Companilactobacillus, Lapidilactobacillus, Agrilactobacillus, Schleiferilactobacillus, Loigolactobacilus, Lacticaseibacillus, Latilactobacillus, Dellaglioa, Liquorilactobacillus, Ligilactobacillus, Lactiplantibacillus, Furfurilactobacillus, Paucilactobacillus, Limosilactobacillus, Fructilactobacillus, Acetilactobacillus, Apilactobacillus, Levilactobacillus, Secundilactobacillus and Lentilactobacillus are proposed. We also propose to emend the description of the family Lactobacillaceae to include all genera that were previously included in families Lactobacillaceae and Leuconostocaceae. The generic term 'lactobacilli' will remain useful to designate all organisms that were classified as Lactobacillaceae until 2020. This reclassification reflects the phylogenetic position of the micro-organisms, and groups lactobacilli into robust clades with shared ecological and metabolic properties, as exemplified for the emended genus Lactobacillus encompassing species adapted to vertebrates (such as Lactobacillus delbrueckii, Lactobacillus iners, Lactobacillus crispatus, Lactobacillus jensensii, Lactobacillus johnsonii and Lactobacillus acidophilus) or invertebrates (such as Lactobacillus apis and Lactobacillus bombicola).A Gram-stain-positive, motile, rod-shaped bacterium, designated strain LAM7113T, was isolated from soil sample collected from a birch forest in Xinjiang Uygur Autonomous Region, PR China. Strain LAM7113T grew optimally at pH 8.0, 30 °C and in the presence of 1.0 % NaCl (w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain LAM7113T was closely related to members of the genus Paenibacillus, with the highest similarity to Paenibacillus baekrokdamisoli Back-11T (96.2 %). The genomic DNA G+C content was 43.4 mol%. The values of average nucleotide identity and DNA-DNA hybridization were 66.1 and 27.0 %, respectively, by comparing the draft genome sequences of strain LAM7113T and P. baekrokdamisoli Back-11T. Anteiso-C15 0 and iso-C15 0 were identified as the major cellular fatty acids. Menaquinone-7 was detected as the predominant respiratory quinone. The major polar lipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, three unidentified aminophospholipids, three unidentified glycolipids, one unidentified phospholipid and two unknown polar lipids. link3 Based on its phenotypic, phylogenetic and chemotaxonomic characteristics, strain LAM7113T is proposed to represent a novel species of the genus Paenibacillus with the name Paenibacillus solisilvae sp. nov. The type strain is LAM7113T (=CGMCC 1.16619T=JCM 32513T).Bi-allelic pathogenic variants in genes of the EIF2B family are responsible for Childhood Ataxia with Central nervous system Hypomyelination/Vanishing White Matter disease, a progressive neurodegenerative disorder of the central white matter. Only seven molecularly proven cases with antenatal onset have been reported so far. We report for the first time the neuropathological findings obtained from two foetuses harbouring deleterious variants in the EIF2B5 gene who presented in utero growth retardation and microcephaly with simplified gyral pattern that led to a medical termination of the pregnancy at 27 and 32 weeks of gestation. Neuropathological examination confirmed microcephaly with delayed gyration, periventricular pseudo-cysts and severe cerebellar hypoplasia. Histologically, the cerebellar cortex was immature, the dentate nuclei were fragmented and myelin stains revealed almost no myelination of the infratentorial structures. Bergmann glia was virtually absent associated to a drastic decreased number of mature astrocytes in the cerebellar white matter, multiple nestin-positive immature astrocytes as well as increased numbers of PDGRFα-positive oligodendrocyte precursors. Whole exome sequencing performed in the two foetuses and their parents allowed the identification of two EIF2B5 compound heterozygous variants in the two foetuses c.468C > G p.Ile156Met and c.1165G > A p.Val389Met, the parents being heterozygous carriers. These variants are absent in the genome Aggregation Database (gnomAD r2.0.2). Contrary to the variant Ile156Met already described in a patient with CACH syndrome, the variant p.Val389Met is novel and predicted to be deleterious using several softwares. Neuropathological findings further expand the phenotypic spectrum of the disease that very likely occurs during early gestation and may manifest from the second half of pregnancy by a severe impairment of cerebral and cerebellar development.BACKGROUND Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes.
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