483 research outputs found

    Projected Increase of the East Asian Summer Monsoon (Meiyu) in Taiwan by Climate Models With Variable Performance

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    The active phase of the East Asian summer monsoon (EASM) in Taiwan during May and June, known as Meiyu, produces substantial precipitation for water uses in all sectors of society. Following a companion study that analysed the historical increase in the Meiyu precipitation, the present study conducted model evaluation and diagnosis based on the EASM lifecycle over Taiwan. Higher and lower skill groups were identified from 17 Couple Model Intercomparison Project Phase 5 (CMIP5) models, with five models in each group. Despite the difference in model performance, both groups projected a substantial increase in the Meiyu precipitation over Taiwan. In the higher skill group, weak circulation changes and reduced low‐level convergence point to a synoptically unfavourable condition for precipitation. In the lower skill group, intensified low‐level southwesterly winds associated with a deepened upper level trough enhance moisture pooling. Thus, the projected increase in Meiyu precipitation will likely occur through the combined effects of (1) the extension of a strengthened North Pacific anticyclone enhancing southwesterlies; and (2) more systematically, the Clausius–Clapeyron relationship that increases precipitation intensity in a warmer climate. The overall increase in the Meiyu precipitation projected by climate models of variable performance supports the observed tendency toward more intense rainfall in Taiwan and puts its early June 2017 extreme precipitation events into perspective

    Anthropogenic sound exposure-induced stress in captive dolphins and implications for cetacean health

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Yang, W.-C., Chen, C.-F., Chuah, Y.-C., Zhuang, C.-R., Chen, I.-H., Mooney, T. A., Stott, J., Blanchard, M., Jen, I.-F., & Chou, L.-S. Anthropogenic sound exposure-induced stress in captive dolphins and implications for cetacean health. Frontiers in Marine Science, 8,(2021): 606736, https://doi.org/10.3389/fmars.2021.606736.Many cetaceans are exposed to increasing pressure caused by anthropogenic activities in their marine environment. Anthropogenic sound has been recognized as a possible stressor for cetaceans that may have impacts on health. However, the relationship between stress, hormones, and cytokines secretion in cetaceans is complex and not fully understood. Moreover, the effects of stress are often inconsistent because the character, intensity, and duration of the stressors are variable. For a better understanding of how anthropogenic sounds affect the psychophysiology of cetaceans, the present study compared the changes of cortisol concentration and cytokine gene transcriptions in blood samples and behaviors of captive bottlenose dolphins (Tursiops truncatus) after sound exposures. The sound stimuli were 800 Hz pure-tone multiple impulsive sound for 30 min at three different sound levels (estimated mean received SPL: 0, 120, and 140 dB re 1 μPa) that likely cause no permanent and temporary hearing threshold shift in dolphins. Six cytokine genes (IL-2Rα, IL-4, IL-10, IL-12, TNF-α, and IFN-γ) were selected for analysis. Cortisol levels and IL-10 gene transcription increased and IFNγ/IL-10 ratio was lower after a 30-min high-level sound exposure, indicating the sound stimuli used in this study could be a stressor for cetaceans, although only minor behavior changes were observed. This study may shed light on the potential impact of pile driving-like sounds on the endocrine and immune systems in cetaceans and provide imperative information regarding sound exposure for free-ranging cetaceans.This work was supported by the Ministry of Science and Technology in Taiwan (MOST 108-2313-B-002-021 and MOST 109-2628-B-002-028)

    Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

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    X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model

    A zwitterionic interpenetrating network for improving the blood compatibility of polypropylene membranes applied to leukodepletion

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    Although widely used in blood-contacting devices, polypropylene (PP) membranes are prone to biofouling by plasma proteins and blood cells. The present study explores the effect of a surface zwitterionization process on the improvement of the biofouling resistance of PP membranes for leukocyte reduction filters. The modification strategy consists in forming an interpenetrating network of poly(glycidyl methacrylate-co-sulfobetaine methacrylate) (poly(GMA-co-SBMA) around the fibers of coated PP membranes, using a cross-linking agent: ethylenediamine (EDA). It is shown that with EDA, a range of poly(GMA-co-SBMA) concentration (1–5 mg/mL) leads to a 0°-water contact angle and high hydration of the networks without affecting the intrinsic porous structure of the material. Besides, the related membranes show excellent resistance to biofouling by Escherichia coli, fibrinogen, leukocytes, erythrocytes, thrombocytes and cells from whole blood with reductions in adsorption of 97%, 86%, 90%, 95%, 97% and 91%, respectively, compared to unmodified PP. Used in whole blood filtration, it is demonstrated that in the best conditions (5 mg/mL copolymer, with EDA), leukocytes can be efficiently removed (>99.99%) without altering the erythrocytes concentration in the permeate, and that leukodepletion is more efficient than that measured with a commercial hydrophilic PP blood filter (about 50% retention). Physical retention of leukocytes is only efficient if the membrane material is anti-biofouling, and so, does not interact with other blood components able to trigger leukocyte attachment/deformation

    Metabolic syndrome and abdominal fat are associated with inflammation, but not with clinical outcomes, in peritoneal dialysis patients

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    BACKGROUND: In the general population, metabolic syndrome (MetS) is correlated with visceral fat and a risk factor for cardiovascular disease (CVD); however, little is known about the significance of abdominal fat and its association with inflammation and medication use in peritoneal dialysis (PD) patients. We investigated the relationship of visceral fat area (VFA) with C-reactive protein (CRP) levels and medication use in PD patients and followed their clinical outcomes. METHODS: In a prospective study from February 2009 to February 2012, we assessed diabetes mellitus (DM) status, clinical and PD-associated characteristics, medication use, CRP levels, components of MetS, and VFA in 183 PD patients. These patients were categorized into 3 groups based on MetS and DM status: non-MetS (group 1, n = 73), MetS (group 2, n = 65), and DM (group 3, n = 45). VFA was evaluated by computed tomography (CT) and corrected for body mass index (BMI). RESULTS: Patients in group 1 had smaller VFAs than patients in groups 2 and 3 (3.2 ± 1.8, 4.6 ± 1.9, and 4.9 ± 2.0 cm(2)/[kg/m(2)], respectively, P < 0.05) and lower CRP levels (0.97 ± 2.31, 1.27 ± 2.57, and 1.11 ± 1.35 mg/dL, respectively, P < 0.05). VFA increased with the number of criteria met for MetS. After adjusting for age, body weight, and sex, CRP and albumin levels functioned as independent positive predictors of VFA; on other hand, the use of renin-angiotensin system blockers was inversely correlated with VFA in PD patients without DM. In the survival analysis, DM patients (group 3) had the poorest survival among the 3 groups, but no significant differences were found between groups 1 and 2. CONCLUSION: This study showed that VFA and MetS are associated with CRP levels but cannot predict survival in PD patients without DM. The complex relationship of nutritional parameters to VFA and MetS may explain these results. The type of antihypertensive medication used was also associated with the VFA. The mechanisms behind these findings warrant further investigation

    High yield expression in a recombinant E. coli of a codon optimized chicken anemia virus capsid protein VP1 useful for vaccine development

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    <p>Abstract</p> <p>Background</p> <p>Chicken anemia virus (CAV), the causative agent chicken anemia, is the only member of the genus <it>Gyrovirus </it>of the <it>Circoviridae </it>family. CAV is an immune suppressive virus and causes anemia, lymph organ atrophy and immunodeficiency. The production and biochemical characterization of VP1 protein and its use in a subunit vaccine or as part of a diagnostic kit would be useful to CAV infection prevention.</p> <p>Results</p> <p>Significantly increased expression of the recombinant full-length VP1 capsid protein from chicken anemia virus was demonstrated using an <it>E. coli </it>expression system. The VP1 gene was cloned into various different expression vectors and then these were expressed in a number of different <it>E. coli </it>strains. The expression of CAV VP1 in <it>E. coli </it>was significantly increased when VP1 was fused with GST protein rather than a His-tag. By optimizing the various rare amino acid codons within the N-terminus of the VP1 protein, the expression level of the VP1 protein in <it>E. coli </it>BL21(DE3)-pLysS was further increased significantly. The highest protein expression level obtained was 17.5 g/L per liter of bacterial culture after induction with 0.1 mM IPTG for 2 h. After purification by GST affinity chromatography, the purified full-length VP1 protein produced in this way was demonstrated to have good antigenicity and was able to be recognized by CAV-positive chicken serum in an ELISA assay.</p> <p>Conclusions</p> <p>Purified recombinant VP1 protein with the gene's codons optimized in the N-terminal region has potential as chimeric protein that, when expressed in <it>E. coli</it>, may be useful in the future for the development of subunit vaccines and diagnostic tests.</p

    Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis

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    BackgroundBreast cancer is the most common cancer type that affects women. In hormone receptor–positive (HR+), human epidermal growth factor receptor 2−negative (HER2–) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population.MethodologyThis is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment.ResultsPIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR−/HER2+ subtype and 42% of patients with HR+/HER2– postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2– premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort.ConclusionA high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes
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