Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

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Reproducibility of non-fasting plasma metabolomics measurements across processing delays

Introduction

Processing delays after blood collection is a common pre-analytical condition in large epidemiologic studies. It is critical to evaluate the suitability of blood samples with processing delays for metabolomics analysis as it is a potential source of variation that could attenuate associations between metabolites and disease outcomes.

Objectives

We aimed to evaluate the reproducibility of metabolites over extended processing delays up to 48 h. We also aimed to test the reproducibility of the metabolomics platform.

Methods

Blood samples were collected from 18 healthy volunteers. Blood was stored in the refrigerator and processed for plasma at 0, 15, 30, and 48 h after collection. Plasma samples were metabolically profiled using an untargeted, ultrahigh performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) platform. Reproducibility of 1012 metabolites over processing delays and reproducibility of the platform were determined by intraclass correlation coefficients (ICCs) with variance components estimated from mixed-effects models.

Results

The majority of metabolites (approximately 70% of 1012) were highly reproducible (ICCs?≥?0.75) over 15-, 30- or 48-h processing delays. Nucleotides, energy-related metabolites, peptides, and carbohydrates were most affected by processing delays. The platform was highly reproducible with a median technical ICC of 0.84 (interquartile range 0.68–0.93).

Conclusion

Most metabolites measured by the UPLC–MS/MS platform show acceptable reproducibility up to 48-h processing delays. Metabolites of certain pathways need to be interpreted cautiously in relation to outcomes in epidemiologic studies with prolonged processing delays.

     

Length‐weight and length‐length relationships of four small fishes from the Atrai River,Dinajpur, Bangladesh

Length‐weight (LWRs) and length‐length relationships (LLRs) were determined for four fish species collected from the Atari River in Dinajpur of Bangladesh. Sampling took place monthly between January and June 2016, using seine nets of commercial fishermen (mesh size 4 mm). In LWRs (r² > .927, p < .05), slope (b) was estimated as 3.191, 2.992, 3.217 and 3.109 for Acanthocobitis botia, Botia lohachata, Canthophrys gongota and Chanda nama, respectively. In LLRs (r² > .812, p < .05), lengths i.e. TL, SL, HL and FL were highly correlated. The present study on these species would be the baseline for FishBase dataset.     

Gamma radiation and interspecific hybridization in jute ( Corchorus capsularis L. and C. olitorius L.)

Although numerous attempts have been made during the last five decades, no hybrids combining the qualities of the two commercially most important species have been released so far. Dry seeds of Corchorus capsularis L. var. D-154 and Corchorus olitorius L. var. C.G. were irradiated with gamma rays of various intensities from 70 Kr. to 100 Kr. and were sown in the field. Abnormal plants of the first generation showing bilobed and crinkled characters in their leaves induced by gamma rays were chosen as male parents. 300 crosses of different combinations were made. In all 120 fruits developed into maturity. All the seeds failed to germinate except those from the crosses ♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) and ♀ D-154 (0 Kr.) × ♂ C.G. (70 Kr.). F₁ plants from the cross ♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) inherited the bilobed character of the male parent whereas the plants from the other cross failed to show any sign of inheritance of the male parent. This indicated that the plants from the cross ♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) were hybrids. These hybrids attained a greater height than the controls and were highly fertile.     

Sulfonamidolactam inhibitors of coagulation factor Xa

As part of an effort to identify novel backups for previously reported pyrazole-based coagulation Factor Xa inhibitors, the pyrazole 5-carboxamide moiety was replaced by 3-(sulfonylamino)-2-piperidone. This led to the identification of a structurally diverse chemotype that was further optimized to incorporate neutral or weakly basic aryl and heteroaryl P1 groups while maintaining good potency versus Factor Xa. Substitution at the sulfonamide nitrogen provided further improvements in potency and as did introduction of alternate P4 moieties.     

Antifouling activity of the sponge metabolite agelasine D and synthesised analogs on Balanus improvisus

This study reports a screening study for antifouling (AF) activity of the natural compound agelasine D isolated from marine sponges of the genus Agelas and 20 synthesised analogs of agelasines and agelasimines. Agelasine D, together with two of the analogs, ie AV1003A and AKB695, displayed a strong inhibitory effect on settlement of Balanus improvisus cypris larvae. Agelasine D had an EC50 value of 0.11 microM while the two analogs AV1033A and AKB695 had EC50 values of 0.23 and 0.3 microM, respectively. None of these three compounds affected larval mortality as was the case with several of the analogs tested. Moreover, the effect of AV1033A and AKB695 was reversible. When cyprids after 24 h exposure to the compounds were transferred to fresh seawater, the settlement frequency compared with the controls was completely recovered. The properties of the agelasine D analogs AV1003A and AKB695 make them highly attractive candidates as AF agents in future marine coatings.     

End joining at Caenorhabditis elegans telomeres

Critically shortened telomeres can be subjected to DNA repair events that generate end-to-end chromosome fusions. The resulting dicentric chromosomes can enter breakage–fusion–bridge cycles, thereby impeding elucidation of the structures of the initial fusion events and a mechanistic understanding of their genesis. Current models for the molecular basis of fusion of critically shortened, uncapped telomeres rely on PCR assays that typically capture fusion breakpoints created by direct ligation of chromosome ends. Here we use independent approaches that rely on distinctive features of Caenorhabditis elegans to study the frequency of direct end-to-end chromosome fusion in telomerase mutants: (1) holocentric chromosomes that allow for genetic isolation of stable end-to-end fusions and (2) unique subtelomeric sequences that allow for thorough PCR analysis of samples of genomic DNA harboring multiple end-to-end fusions. Surprisingly, only a minority of end-to-end fusion events resulted from direct end joining with no additional genome rearrangements. We also demonstrate that deficiency for the C. elegans Ku DNA repair heterodimer does not affect telomere length or cause synthetic effects in the absence of telomerase.     

Genomic analysis of adaptive differentiation in Drosophila melanogaster

Drosophila melanogaster shows clinal variation along latitudinal transects on multiple continents for several phenotypes, allozyme variants, sequence variants, and chromosome inversions. Previous investigation suggests that many such clines are due to spatially varying selection rather than demographic history, but the genomic extent of such selection is unknown. To map differentiation throughout the genome, we hybridized DNA from temperate and subtropical populations to Affymetrix tiling arrays. The dense genomic sampling of variants and low level of linkage disequilibrium in D. melanogaster enabled identification of many small, differentiated regions. Many regions are differentiated in parallel in the United States and Australia, strongly supporting the idea that they are influenced by spatially varying selection. Genomic differentiation is distributed nonrandomly with respect to gene function, even in regions differentiated on only one continent, providing further evidence for the role of selection. These data provide candidate genes for phenotypes known to vary clinally and implicate interesting new processes in genotype-by-environment interactions, including chorion proteins, proteins regulating meiotic recombination and segregation, gustatory and olfactory receptors, and proteins affecting synaptic function and behavior. This portrait of differentiation provides a genomic perspective on adaptation and the maintenance of variation through spatially varying selection.     

PARC6, a novel chloroplast division factor, influences FtsZ assembly and is required for recruitment of PDV1 during chloroplast division in Arabidopsis

Chloroplast division in plant cells is accomplished through the coordinated action of the tubulin-like FtsZ ring inside the organelle and the dynamin-like ARC5 ring outside the organelle. This coordination is facilitated by ARC6, an inner envelope protein required for both assembly of FtsZ and recruitment of ARC5. Recently, we showed that ARC6 specifies the mid-plastid positioning of the outer envelope proteins PDV1 and PDV2, which have parallel functions in dynamin recruitment. PDV2 positioning involves direct ARC6–PDV2 interaction, but PDV1 and ARC6 do not interact indicating that an additional factor functions downstream of ARC6 to position PDV1. Here, we show that PARC6 (paralog of ARC6), an ARC6-like protein unique to vascular plants, fulfills this role. Like ARC6, PARC6 is an inner envelope protein with its N-terminus exposed to the stroma and Arabidopsis parc6 mutants exhibit defects of chloroplast and FtsZ filament morphology. However, whereas ARC6 promotes FtsZ assembly, PARC6 appears to inhibit FtsZ assembly, suggesting that ARC6 and PARC6 function as antagonistic regulators of FtsZ dynamics. The FtsZ inhibitory activity of PARC6 may involve its interaction with the FtsZ-positioning factor ARC3. A PARC6–GFP fusion protein localizes both to the mid-plastid and to a single spot at one pole, reminiscent of the localization of ARC3, PDV1 and ARC5. Although PARC6 localizes PDV1, it is not required for PDV2 localization or ARC5 recruitment. Our findings indicate that PARC6, like ARC6, plays a role in coordinating the internal and external components of the chloroplast division complex, but that PARC6 has evolved distinct functions in the division process.