Cryo-EM model validation recommendations based on outcomes of the 2019 EMDataResource challenge

This paper describes outcomes of the 2019 Cryo-EM Model Challenge. The goals were to (1) assess the quality of models that can be produced from cryogenic electron microscopy (cryo-EM) maps using current modeling software, (2) evaluate reproducibility of modeling results from different software developers and users and (3) compare performance of current metrics used for model evaluation, particularly Fit-to-Map metrics, with focus on near-atomic resolution. Our findings demonstrate the relatively high accuracy and reproducibility of cryo-EM models derived by 13 participating teams from four benchmark maps, including three forming a resolution series (1.8 to 3.1 Å). The results permit specific recommendations to be made about validating near-atomic cryo-EM structures both in the context of individual experiments and structure data archives such as the Protein Data Bank. We recommend the adoption of multiple scoring parameters to provide full and objective annotation and assessment of the model, reflective of the observed cryo-EM map density

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis.In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo.These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19

Influence of High Voltage Insulator on Pollution Flashover Voltage

Results of pollution flashover voltage measurements and optical observation obtained for high voltage insulators placed in the vertical and the horizontal positions are presented. H was found that the well known difference between flashover voltages measured in tests of insulators placed in these positions was a function of the mean contaminant thickness and the uniformity of layer distribution on the insulators. On the basis of measurements of the ESDD conducted on insulators subjected to prolonged, natural contamination, their self-cleaning, in the vertical and horizontal positions, was determined

Influence of pollution layer thickness on flashover voltage of HV insulators

The pollution characteristics (the relationships of flashover voltage and SDD or maximum current Imax ) for insulators contaminated with uniform or nonuniform coatings with different thickness h are presented. The influence of the power of test voltage supply and the thickness as well uniformity of the pollution layer on obtained results of measurements is assessed. The flashover voltage and current registrations on a cap and pin insulator string are discussed for different thickness of pollution layer

Influence of pollution layer thickness on flashover voltage of HV insulators

The pollution characteristics (the relationships of flashover voltage and SDD or maximum current Imax ) for insulators contaminated with uniform or nonuniform coatings with different thickness h are presented. The influence of the power of test voltage supply and the thickness as well uniformity of the pollution layer on obtained results of measurements is assessed. The flashover voltage and current registrations on a cap and pin insulator string are discussed for different thickness of pollution layer

Initial growth and development of selected lawn varieties of Lolium perenne in various habitat conditions

The study presents the assessment of initial growth and development of three Lolium perenne L. varieties (Natara, Nira and Taya) in two research series, in two habitats: A – in Sosnowica, at the Didactic-Research Station of the Department of Grassland and Landscape Forming, University of Life Sciences in Lublin and B – on the embankment of National Road No. 17 alongside the Piaski-Łopiennik stretch. In laboratory conditions, thousand grain weight (TGW) and grain germination capacity (in %) were assessed, while in field conditions the seedling growth and root elongation rate (mm) were assessed on the 20th, 40th and 60th day from the sowing date. The responses of the studied varieties to soil conditions were different. Regardless of the research series, the fastest seedling growth rate on mineral soil (habitat A) was observed for the Nira variety while on anthropogenic soil with an undeveloped profile (habitat B) – for the Natara variety. Regardless of the soil and weather conditions in both research series, the highest seedlings and longest roots were found in the Nira variety