Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10⁻⁵) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.     

Active control of locomotion facilitates nonvisual navigation.

In some navigation tasks, participants are more accurate if they view the environment beforehand. To characterize the benefits associated with visual previews, 32 blindfolded participants were guided along simple paths and asked to walk unassisted to a specified destination (e.g., the origin). Paths were completed without vision, with or without a visual preview of the environment. Previews did not necessarily improve nonvisual navigation. When previewed landmarks stood near the origin or at off-path locations, they provided little benefit; by contrast, when they specified intermediate destinations (thereby increasing the degree of active control), performance was greatly enhanced. The results suggest that the benefit of a visual preview stems from the information it supplies for actively controlled locomotion. Accuracy in reaching the final destination, however, is strongly contingent upon the destination's location during the preview. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Haptic integration of planar size with hardness, texture, and planar contour.

Three experiments involving a total of 75 college students investigated the role of size information in haptic classification of custom-made planar objects when size covaries with hardness, texture, or planar contour. Exp 1 showed facilitation of classification by redundant (RD) size and shape cues, indicating the coprocessing of size and shape. Exps 2 and 3 used a withdrawal paradigm: Classification trials began with 2 RD properties, and 1 was then held constant (withdrawn). Exp 2 showed that when size and shape were RD, withdrawal of either impaired responses, whereas when size was RD with texture or hardness, only size withdrawal had an effect. Exp 3 demonstrated that this size weighting was not restricted to a single procedure for exploration. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial updating of locations specified by 3-D sound and spatial language.

Blind and blindfolded sighted observers were presented with auditory stimuli specifying target locations. The stimulus was either sound from a loudspeaker or spatial language (e.g., "2 o'clock, 16 ft"). On each trial, an observer attempted to walk to the target location along a direct or indirect path. The ability to mentally keep track of the target location without concurrent perceptual information about it (spatial updating) was assessed in terms of the separation between the stopping points for the 2 paths. Updating performance was very nearly the same for the 2 modalities, indicating that once an internal representation of a location has been determined, subsequent updating performance is nearly independent of the modality used to specify the representation. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Synthesis and Antiplasmodial Activity of Novel Chloroquine Analogues with Bulky Basic Side Chains

Chloroquine is commonly used in the treatment and prevention of malaria, but Plasmodium falciparum, the main species responsible for malaria‐related deaths, has developed resistance against this drug. Twenty‐seven novel chloroquine (CQ) analogues characterized by a side chain terminated with a bulky basic head group, i.e., octahydro‐2H‐quinolizine and 1,2,3,4,5,6‐hexahydro‐1,5‐methano‐8H‐pyrido[1,2‐a][1,5]diazocin‐8‐one, were synthesized and tested for activity against D‐10 (CQ‐susceptible) and W‐2 (CQ‐resistant) strains of P. falciparum. Most compounds were found to be active against both strains with nanomolar or sub‐micromolar IC₅₀ values. Eleven compounds were found to be 2.7‐ to 13.4‐fold more potent than CQ against the W‐2 strain; among them, four cytisine derivatives appear to be of particular interest, as they combine high potency with low cytotoxicity against two human cell lines (HMEC‐1 and HepG2) along with easier synthetic accessibility. Replacement of the 4‐NH group with a sulfur bridge maintained antiplasmodial activity at a lower level, but produced an improvement in the resistance factor. These compounds warrant further investigation as potential drugs for use in the fight against malaria.     

Integration of InGaP/GaAs/Ge triple‐junction solar cells on deeply patterned silicon substrates

We report preliminary results on InGaP/InGaAs/Ge photovoltaic cells for concentrated terrestrial applications, monolithically integrated on engineered Si(001) substrates. Cells deposited on planar Ge/Si(001) epilayers, grown by plasma‐enhanced chemical vapor deposition, provide good efficiency and spectral response, despite the small thickness of the Ge epilayers and a threading dislocation density as large as 10⁷/cm². The presence of microcracks generated by the thermal misfit is compensated by a dense collection grid that avoids insulated areas. In order to avoid the excessive shadowing introduced by the use of a dense grid, the crack density needs to be lowered. Here, we show that deep patterning of the Si substrate in blocks can be an option, provided that a continuous Ge layer is formed at the top, and it is suitably planarized before the metalorganic chemical vapor deposition. The crack density is effectively decreased, despite that the efficiency is also lowered with respect to unpatterned devices. The reasons of this efficiency reduction are discussed, and a strategy for improvement is proposed and explored. Full morphological analysis of the coalesced Ge blocks is reported, and the final devices are tested under concentrated AM1.5D spectrum. Copyright © 2016 John Wiley & Sons, Ltd.     

Yeast vectors for the integration/expression of any sequence at the TYR1 locus

We have constructed new yeast vectors for targeted integration and conditional expression of any sequence at the Saccharomyces cerevisiae TYR1 locus which becomes disrupted. We show that vector integration is not neutral, causing prototrophy for tyrosine and auxotrophy for the vector's selectable marker (uracil or leucine, depending on the vector used). This feature allows a double screening of transformed yeast cells, improving the identification of colonies with the desired chromosomal structure. The GAL10 gene promoter has been added to drive conditional expression of cloned sequences. Using these vectors, chromosomal structure verification of recombinant clones is no longer necessary, since the noise of non-homologous recombination, as well as spontaneous reversion of the selected phenotype, can easily be identified. The ability of the vector to conditionally control gene expression has been confirmed using the gene for the green fluorescent protein (GFP) as a reporter.