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Background The primary pathological alterations of Pendred syndrome are endolymphatic pH acidification and luminal enlargement of the inner ear. However, the molecular contributions of specific cell types remain poorly characterized. Therefore, we aimed to identify pH regulators in pendrin-expressing cells that may contribute to the homeostasis of endolymph pH and define the cellular pathogenic mechanisms that contribute to the dysregulation of cochlear endolymph pH in Slc26a4 −/− mice. Methods We used single-cell RNA sequencing to identify both Slc26a4 -expressing cells and Kcnj10 -expressing cells in wild-type (WT, Slc26a4 +/+ ) and Slc26a4 −/− mice. Bioinformatic analysis of expression data confirmed marker genes defining the different cell types of the stria vascularis. In addition, specific findings were confirmed at the protein level by immunofluorescence. Results We found that spindle cells, which express pendrin, contain extrinsic cellular components, a factor that enables cell-to-cell communication. In addition, the gene expression profile informed the pH of the spindle cells. Compared to WT, the transcriptional profiles in Slc26a4 −/− mice showed downregulation of extracellular exosome-related genes in spindle cells. Immunofluorescence studies in spindle cells of Slc26a4 −/− mice validated the increased expression of the exosome-related protein, annexin A1, and the clathrin-mediated endocytosis-related protein, adaptor protein 2. Conclusion Overall, cell isolation of stria vascularis from WT and Slc26a4 −/− samples combined with cell type-specific transcriptomic analyses revealed pH-dependent alternations in spindle cells and intermediate cells, inspiring further studies into the dysfunctional role of stria vascularis cells in SLC26A4 -related hearing loss.

Autosomal-dominant, early-onset DYT1 dystonia is associated with an in-frame deletion of a glutamic acid codon (ΔE) in the TOR1A gene. The gene product, torsinA, is an evolutionarily conserved AAA+ ATPase. The fact that constitutive secretion from patient fibroblasts is suppressed indicates that the ΔE-torsinA protein influences the cellular secretory machinery. However, which component is affected remains unclear. Prompted by recent reports that abnormal protein trafficking through the Golgi apparatus, the major protein-sorting center of the secretory pathway, is sometimes associated with a morphological change in the Golgi, we evaluated the influence of ΔE-torsinA on this organelle. Specifically, we examined its structure by confocal microscopy, in cultures of striatal, cerebral cortical and hippocampal neurons obtained from wild-type, heterozygous and homozygous ΔE-torsinA knock-in mice. In live neurons, the Golgi was assessed following uptake of a fluorescent ceramide analog, and in fixed neurons it was analyzed by immuno-fluorescence staining for the Golgi-marker GM130. Neither staining method indicated genotype-specific differences in the size, staining intensity, shape or localization of the Golgi. Moreover, no genotype-specific difference was observed as the neurons matured in vitro. These results were supported by a lack of genotype-specific differences in GM130 expression levels, as assessed by Western blotting. The Golgi was also disrupted by treatment with brefeldin A, but no genotype-specific differences were found in the immuno-fluorescence staining intensity of GM130. Overall, our results demonstrate that the ΔE-torsinA protein does not drastically influence Golgi morphology in neurons, irrespective of genotype, brain region (among those tested), or maturation stage in culture. While it remains possible that functional changes in the Golgi exist, our findings imply that any such changes are not severe enough to influence its morphology to a degree detectable by light microscopy.

Background Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear. Methods Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort ( N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores. Results We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all p < 0.05 ), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ( ρ = 0.19 , p = 0.004 ; ρ = 0.2 , p = 0.004 , respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ( t = 4.0 , p = 8.8 × 10 - 5 ), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ( t = - 3.3 , p = 0.001 ). Finally, using the SPARK cohort ( N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ( t = - 2.3 , p = 0.02 , and t = 4.2 , p = 3.2 × 10 - 5 for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: - 0.22 ± 0.05 ; testosterone: - 0.35 ± 0.15 from 0.1%-ile to 99.9%-ile; SHBG: 0.64 ± 0.15 from 0.1%-ile to 99.9%-ile). Limitations In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules. Conclusions These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females.

DYT1 dystonia is the most common hereditary form of primary torsion dystonia. This autosomal-dominant disorder is characterized by involuntary muscle contractions that cause sustained twisting and repetitive movements. It is caused by an in-frame deletion in the TOR1A gene, leading to the deletion of a glutamic acid residue in the torsinA protein. Heterozygous knock-in mice, which reproduce the genetic mutation in human patients, have abnormalities in synaptic transmission at the principal GABAergic neurons in the striatum, a brain structure that is involved in the execution and modulation of motor activity. However, whether this mutation affects the excitability of striatal GABAergic neurons has not been investigated in this animal model. Here, we examined the excitability of cultured striatal neurons obtained from heterozygous knock-in mice, using calcium imaging as indirect readout. Immunofluorescence revealed that more than 97% of these neurons are positive for a marker of GABAergic neurons, and that more than 92% are also positive for a marker of medium spiny neurons, indicating that these are mixed cultures of mostly medium spiny neurons and a few (~5%) GABAergic interneurons. When these neurons were depolarized by field stimulation, the calcium concentration in the dendrites increased rapidly and then decayed slowly. The amplitudes of calcium transients were larger in heterozygous neurons than in wild-type neurons, resulting in ~15% increase in cumulative calcium transients during a train of stimuli. However, there was no change in other parameters of calcium dynamics. Given that calcium dynamics reflect neuronal excitability, these results suggest that the mutation only slightly increases the excitability of striatal GABAergic neurons in DYT1 dystonia.

Eight lichen species, Cetraria aculeata, Cladonia furcata, Pseudephebe pubescens, Sphaerophorus globosus, Stereocaulon alpinum, Umbilicaria antarctica, Usnea antarctica and Usnea aurantiacoatra, were collected from King George Island, maritime Antarctica, for the evaluation of antioxidant activities. Anti-linoleic acid peroxidation activity, free radical scavenging activity, reducing power and superoxide anion scavenging activity were assessed of methanol and acetone extract of the lichens in vitro. Extract of Umbilicaria antarctica, Cladonia furcata, Sphaerophorus globosus and Usnea antarctica were found to have strong in vitro antioxidant properties. In general, acetone extract exhibited stronger activities than methanol extract. The activity-guided bioautographic TLC and HPLC analysis demonstrated that lecanoric acid was the main antioxidant compound in the acetone extract of Umbilicaria antarctica, the most potent antioxidant lichen species among the test species. The results suggested that several Antarctic lichens and their substances can be used as novel bioresources of natural antioxidants.

Bryophytes comprise one of the richest microfungal microhabitats in the Antarctic environment. The maritime Antarctic is very vulnerable to rapid environmental change caused by global warming. The aim of this study was to investigate the importance of bryophytes as a microhabitat for fungal species in the maritime Antarctic by surveying endophytic fungal diversity from several bryophytes including Andreaea sp., Barbilophozia hatcheri , Chorisodontium aciphyllum , Polytrichum alpinum , Polytrichum strictum , Sanionia uncinata , and Warnstorfia sarmentosa . We collected 13 bryophyte samples at four localities on Barton Peninsula, King George Island. In total, 31 endophytic fungi morphotypes were isolated from bryophyte tissues by a thorough surface sterilization method. Using internal transcribed spacer sequence analysis, 16 endophytic fungal strains belonging to Ascomycota (12), Basidiomycota (1), Oomycota (1), and Zygomycota (2) phyla were obtained. Our results suggest the presence of a diverse range of fungal species even in a very limited area, and those bryophytes play an important role in conserving fungal diversity in this harsh environment. Growth rate measurements at a wide range of temperatures confirmed that most of the fungal strains were both mesophilic and psychrotolerant. This is the first report of endophytic fungi in Antarctic moss tissue by fluorescence in situ hybridization.

The current cut-off value for diagnosing exercise-induced bronchoconstriction (EIB) in adults—percent fall in FEV 1 (ΔFEV 1 ) ≥ 10% after exercise challenge test (ECT)—has low specificity and weak evidences. Therefore, this study aimed to identify the cut-off value for EIB that provides the highest diagnostic sensitivity and specificity. Participants who underwent the ECT between 2007 and 2018 were categorized according to ΔFEV 1 : definite EIB (ΔFEV 1 ≥ 15%), borderline (10% ≤ ΔFEV 1 < 15%), and normal (ΔFEV 1 < 10%). Distinct characteristics of the definite EIB group were identified and explored in the borderline EIB group. A receiver operating characteristic curve was plotted to determine the optimal cut-off value. Of 128 patients, 60 were grouped as the definite EIB group, 23 as the borderline group, and 45 as the normal group. All participants were men, with a median age of 20 years (interquartile range [IQR:] 19–23 years). The definite EIB group exhibited wheezing on auscultation ( P < 0.001), ΔFEV 1 /FVC ≥ 10% ( P < 0.001), and ΔFEF 25–75% ≥ 25% ( P < 0.001) compared to other groups. Eight (8/23, 34.8%) patients in the borderline group had at least one of these features, but the trend was more similar to that of the normal group than the definite EIB group. A cut-off value of ΔFEV 1 ≥ 13.5% had a sensitivity of 98.5% and specificity of 93.5% for EIB. Wheezing on auscultation, ΔFEV 1 /FVC ≥ 10%, and ΔFEF 25–75% ≥ 25% after ECT may be useful for the diagnosis of EIB, particularly in individuals with a ΔFEV 1 of 10–15%. For EIB, a higher cut-off value, possibly ΔFEV 1 ≥ 13.5%, should be considered as the diagnostic criterion.

Brassica rapa (chinese cabbage) is one of the main vegetable crops grown in Asian countries. Pectobacterium carotovorum subsp. carotovorum causes severe economic loss in this crop as well as in other Brassica crops through soft rot disease. Cysteine proteases like bromelain, papain or ficin show toxic effects to herbivorous insects and pathogenic bacteria. They have been known to be critical factors in plant defence mechanisms. The current study investigated the effect of bromelain gene (BL1) of pineapple (Ananas comosus L. Merrill) on enhancing resistance to soft rot in transgenic Brassica rapa ‘Seoulbaechu’. Three homozygous T₂ lines were inoculated with Pectobacterium carotovorum subsp. carotovorum and BL8-2 line showed the lowest rate of infected leaves (RIL) in both wound inoculation and non-wound inoculation, when the non-infected line showed 100 % RIL in both cases. The highest expression of BL1 gene was also observed in BL8-2 homozygous line. Thus, the over-expressed BL1 gene conferred enhanced resistance to soft rot in Brassica rapa.

Efficient control of Xanthomonas arboricola pv. pruni , the causal agent of bacterial spot on stone fruit, requires a sensitive and reliable diagnostic tool. A PCR detection method that utilizes primers to target the hrp gene cluster region was developed in this study. The nucleotide sequence of the PCR product amplified with primers specific for the hrp region of the xanthomonads and genomic DNA of X. arboricola pv. pruni was determined, and the sequence was aligned with that of X. campestris pv. campestris , which was obtained from the GenBank database. On the basis of the sequence of the amplified hrp region, a PCR primer set of XapF/R specific to X. arboricola pv. pruni was designed. This primer set yielded a 243-bp product from the genomic DNA of X. aboricola pv. pruni strains, but no products from other 21 strains of Xanthomonas or from two epiphytic bacterial species. Southern blot hybridization with the probe derived from the PCR product with the primer set and X. aboricola pv. pruni DNA confirmed the PCR results. The Xap primer system was successfully applied to detect the pathogen from infected peach fruits. When it was applied in field samples, the primer set was proved as a reliable diagnostic tool for specific detection of X. aboricola pv. pruni from peach orchards.

Eleven species are recognized of which C. bogilana and C. subflavorubescens are described here as new to science while nine species (C. cinnabarina, C. decipiens, C. ferruginea, C. inconspecta, C. pellodella, C. scopularis, C. stantonii, C. squamosa and C. subsoluta) are reported for the first time for South Korea. Both new species are peculiar due to their secondary chemistry; anthraquinones along with atranorin, gyrophoric acid and lecanoric acid in C. bogilana, and gyrophoric acid together with anthraquinones in C. subflavorubescens.