Condensation of the fusion focus by the intrinsically disordered region of the formin Fus1 is essential for cell-cell fusion

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Time dependent decline of neutralizing antibody titers in COVID-19 patients from Pune,India and evidence of reinfection

PurposeTo assess modulation of neutralizing antibody titers in COVID-19 patients and understand association of variables such as age, presence of comorbidity, BMI and gender with antibody titers.MethodsPatients (n = 100) diagnosed from 20th March 2020 to 17th August 2020 and treated at two large hospitals from Pune, India were included and followed up (clinical and serologic) for varied periods. IgG-anti-SARS-CoV-2 (Spike protein-based ELISA) and neutralizing antibody titers (NAb, PRNT) were determined in all the samples.ResultsOf the 100 patients enrolled initially (median 60 days of diagnosis), follow up samples were collected from 70 patients (median 106 days of diagnosis). Overall, NAb titers reduced significantly (p < 0.001) and as early as 3–4 months. During two visits, 20% and 7.1% patients reported some symptoms. At the first visit, NAb titers were higher in patients with severe disease (p < 0.001), comorbidities (p < 0.005), age <50 years (p < 0.05) and male gender (p < 0.05). Multivariate analysis identified older age (p < 0.001), duration post-diagnosis and female gender as independent variables influencing NAb titers (negative correlation, p < 0.05). During the follow-up, reduction in NAb titers was recorded in patients with comorbidity (p < 0.05), mild disease (p < 0.05), age <50 years (p < 0.05), higher BMI (p < 0.05) and male gender (p < 0.001). Serology identified six cases of asymptomatic reinfections.ConclusionsDecline of NAb titers was associated with age <50 years, mild disease, comorbidities, higher BMI and male gender. At the time of follow up, 8/70 (11.4%) patients lacked neutralizing antibodies. Evidence of 6 probable asymptomatic reinfections suggests waning of immunity, but, probable protection from clinical disease needing hospitalization.     

Elevated PAF1-RAD52 axis confers chemoresistance to human cancers

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TERRA and RAD51AP1 promote alternative lengthening of telomeres through an R- to D-loop switch

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High risk water pollution hazards affecting Aveiro coastal lagoon (Portugal) – A habitat risk assessment using InVEST

Anthropogenic pressures put at jeopardy ecosystem services (ES) provided by natural habitats. Ecosystem Based Management (EBM) approaches can support policymakers dealing with physical, chemical, and biological stresses caused by high-risk water pollution (HRWP) and sudden-accidental pollution (SAP). The objective of this study is to evaluate how alarming HRWP pressures might become in fragile marine, coastal, estuarine, and freshwater socio-ecological systems (MCEF-SES) surrounded by heavily industrialized and urbanized areas. To this end a spatially explicit analysis, using the InVEST-Habitat Risk Assessment (InVEST-HRA) model in combination with expert judgement from researchers from various fields, is performed. An application is provided for the case of the Ria de Aveiro (RdA) coastal lagoon in Portugal. Results show high spatial variance of HRWP hazards across RdA, with one major multi-layer risk hotspot at the center of the research area and a second patch of multiple risk hotspots towards the North of RdA. Salines emerge as the most threatened habitat followed by Intertidal flats and Saltmarshes. The most significant water pollution risk sources contributing to Salines cumulative risk are Fossil fuel processing, storage and sale units, Industrial units, Aquaculture, and the Marinas. Industries involving dangerous substances in the region threaten primarily Watercourses. This study confirms the InVEST-HRA model in combination with expert judgement is a transparent and easily replicable approach to build ES-based knowledge about habitat risks threatening MCEF-SES in a Natura 2000 site heavily pressured by HRWP hazards. After further valuation analysis, pondering gains and losses from regional development and environmental protection, this knowledge can support the planning and management of coastal areas and the prioritization of pollution abatement interventions. In particular, by estimating the loss that HRWP causes in the value of ecosystem services, defining HRWP abatement policies, assessing the effectiveness, costs and benefits of those abatement policies and, ultimately, evaluating the results for the well-being of local communities through global efficiency analysis, cost-benefit analysis or cost-effectiveness analysis. Hence, it bridges the gap between an informed EBM and the development policies of fragile regions.     

Intravoxel incoherent motion radiomics nomogram for predicting tumor treatment responses in nasopharyngeal carcinoma

BackgroundIntravoxel incoherent motion (IVIM) plays an important role in predicting treatment responses in patient with nasopharyngeal carcinoma (NPC). The goal of this study was to develop and validate a radiomics nomogram based on IVIM parametric maps and clinical data for the prediction of treatment responses in NPC patients.MethodsEighty patients with biopsy-proven NPC were enrolled in this study. Sixty-two patients had complete responses and 18 patients had incomplete responses to treatment. Each patient received a multiple b-value diffusion-weighted imaging (DWI) examination before treatment. Radiomics features were extracted from IVIM parametric maps derived from DWI image. Feature selection was performed by the least absolute shrinkage and selection operator method. Radiomics signature was generated by support vector machine based on the selected features. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) values were used to evaluate the diagnostic performance of radiomics signature. A radiomics nomogram was established by integrating the radiomics signature and clinical data.ResultsThe radiomics signature showed good prognostic performance to predict treatment response in both training (AUC = 0.906, P<0.001) and testing (AUC = 0.850, P<0.001) cohorts. The radiomic nomogram established by integrating the radiomic signature with clinical data significantly outperformed clinical data alone (C-index, 0.929 vs 0.724; P<0.0001).ConclusionsThe IVIM-based radiomics nomogram provided high prognostic ability to treatment responses in patients with NPC. The IVIM-based radiomics signature has the potential to be a new biomarker in prediction of the treatment responses and may affect treatment strategies in patients with NPC.     

Stimulation of lymphocytes from subacute sclerosing panencephalitis patients by defined measles virus antigens

The lymphoproliferative response of human peripheral blood mononuclear cells to different measles virus antigen preparations was studied with lymphocytes from 38 measlesseropositive healthy donors and 4 subacute sclerosing panencephalitis patients. The response was very weak or absent in all of the controls and in three of the subacute sclerosing panencephalitis patients. The fourth subacute sclerosing panencephalitis patient had fluctuating levels of lymphocyte stimulation by measles antigens. The response was very strong for several months and during this time the parameters of the test system were characterized. It was discovered that a membrane preparation of measles-infected cells caused stimulation equal to that of highly purified virions. Purified measles ribonucleoprotein also induced specific stimulation, although lower than that seen with other types of measles antigens. Results of experiments on stimulation kinetics and antigen dose responses were compatible with antigen-specific stimulation. Enriched T cells were more vigorously stimulated than unfractionated peripheral blood mononuclear cells suggesting that this transformation test is specific for T cells.