Identifying a dynamic transcriptomic landscape of the cynomolgus macaque placenta during pregnancy at single-cell resolution

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A systemic insight into astrocytoma biology across different grades

Astrocytomas are the most common type of brain tumors, which originate from glial cells, and are classified into specific grades based on their histopathological behavior. To develop precise therapeutic strategies for the disease, it is important to identify the molecular signatures specific to each grade as well as the key factors responsible for the transition from one grade to the next. In this study, we have taken a systems approach to investigate the gene expression profiles of each grades of the disease by mapping shortest paths of gene interaction in each grade and also between one grade and the next. Module core genes govern the topology of these networks and serve as important functional players in each grade as well as help in grade transition events. Shortlisted among these module core genes are well-characterized players of glioma as well as novel molecules (32 grade-specific genes and 15 grade transition–specific genes), which influence important prooncogenic functions but have not been linked to glioma biology yet. These module core genes provide interesting insight into the biology of astrocytic tumors and are potential therapeutic targets for astrocytoma.     

A New Catalog of Structural Variants in 1,301 A. thaliana Lines from Africa,Eurasia, and North America Reveals a Signature of Balancing Selection at Defense Response Genes

Genomic variation in the model plant Arabidopsis thaliana has been extensively used to understand evolutionary processes in natural populations, mainly focusing on single-nucleotide polymorphisms. Conversely, structural variation has been largely ignored in spite of its potential to dramatically affect phenotype. Here, we identify 155,440 indels and structural variants ranging in size from 1 bp to 10 kb, including presence/absence variants (PAVs), inversions, and tandem duplications in 1,301 A. thaliana natural accessions from Morocco, Madeira, Europe, Asia, and North America. We show evidence for strong purifying selection on PAVs in genes, in particular for housekeeping genes and homeobox genes, and we find that PAVs are concentrated in defense-related genes (R-genes, secondary metabolites) and F-box genes. This implies the presence of a “core” genome underlying basic cellular processes and a “flexible” genome that includes genes that may be important in spatially or temporally varying selection. Further, we find an excess of intermediate frequency PAVs in defense response genes in nearly all populations studied, consistent with a history of balancing selection on this class of genes. Finally, we find that PAVs in genes involved in the cold requirement for flowering (vernalization) and drought response are strongly associated with temperature at the sites of origin.     

Unveiling an abundant core microbiota in the human adult colon by a phylogroup-independent searching approach

The potential presence of widespread and stable bacterial core phylogroups in the human colon has promoted considerable attention. Despite major efforts, no such phylogroups have yet been identified. Therefore, using a novel phylogroup- and tree-independent approach, we present a reanalysis of 1 114 722 V2 region and 71 550 near full-length 16S rRNA sequences from a total of 210 human beings, with widespread geographic origin, ethnic background and diet, in addition to a wide range of other mammals. We found two highly prevalent core phylogroups (cores 1 and 2), belonging to the clostridial family Lachnospiraceae. These core phylogroups showed a log-normal distribution among human individuals, while non-core phylogroups showed more skewed distributions towards individuals with low levels compared with the log-normal distribution. Molecular clock analyses suggest that core 2 co-evolved with the radiation of vertebrates, while core 1 co-evolved with the mammals. Taken together, the stability, prevalence and potential functionality support the fact that the identified core phylogroups are pivotal in maintaining gut homeostasis and health.     

Oxysterols in cap and core of human advanced atherosclerotic lesions

Objective: Different parts of the advanced atherosclerotic lesion have characteristic differences in lipid content, but the distribution of lipid oxidation products has not been reported. This study provides novel data on oxysterol and hydroxyoctadecadienoic acids quantification in core versus cap. It compares the lipid composition of core and cap to assess the topographical distribution of evidence of lipid oxidation.

Methods: Lipids and oxidised lipids were analysed by gas chromatography (GC) and GC-mass spectrometry (GC-MS) in samples of human atheromatous lipid core and fibrous cap of individual advanced atherosclerotic plaques (Stary, Type V) in necropsy samples.

Results: The total lipid was of course massively greater in the core than in the cap. The oxidation products, cholest-5-en-3β,26-diol (26-OH-CHOL) and cholest-5-en-3β,7β-diol (7β-OH-CHOL) were detected in all the samples. 26-OH-CHOL was more abundant in the core than in the cap when related both to wet weight and to cholesterol. 7β-OH-CHOL levels were significantly higher in the core than in the cap when related to wet weight but not when related to cholesterol. Because the processing included a sodium borohydride reduction step, the 7β-OH-CHOL detected could partly originate from 7-ketocholesterol or 7-hydroperoxy-cholesterol. Several isomeric hydroxyoctadecadienoic acids were detected in both core and cap, more in the cap when related to cholesterol content. Most of the components of the cap showed a high degree of cross-correlation on linear regression analysis, but cross-correlations were weaker for the core. The core samples contained a larger proportion of linoleate relative to oleate than the fibrous cap.

Conclusion: The findings suggest that the different lipid and oxidised lipid contents of cap and core may be due to variations in oxidative activity in different parts of the lesion.     

Inhibition of the elongation step of protein synthesis by vaccinia virus

Vaccinia cores inhibit translation in cell-free protein synthesis systems at two stages: initiation; and, as shown here, elongation. The former effect tends to obscure the latter. Elongation control could, however, be revealed as follows: when, in a reticulocyte of L-cell lysate, initiation was blocked by a drug (edein), the residual [35S]methionine incorporation was severely reduced by the subsequent addition of vaccinia cores. The elongation block could also be demonstrated by analysis of ribosome profiles: treatment with edein alone permitted ribosomal run-off; treatment with either the elongation inhibition anisomycin or with cores preserved the polyribosomes.     

Physiological significance of 3-h bright and dim light exposure prior to taking a bath for core and forehead skin temperatures and heart rate during 1-h bathing of 38.5°C

1. The study investigated the effect of exposure to 3-h bright light (2500 lx) or dim light (200 lx) just prior to taking a hot bath upon thermophysiological responses during the 1-h bath (at 38.5°C water temperature). 2. Core and forehead skin temperature increases during the bath were significantly lower after bright than after dim light exposure. 3. Heart rate during the bath was significantly lower after exposure to bright light than dim light. 4. These results are discussed in terms of a reduced set-point of core temperature due to a probable higher secretion of melatonin under the bright light condition.     

Molecular links between the E2 envelope glycoprotein and nucleocapsid core in Sindbis virus

A three-dimensional reconstruction of Sindbis virus at 7.0 Å resolution presented here provides a detailed view of the virion structure and includes structural evidence for key interactions that occur between the capsid protein (CP) and transmembrane (TM) glycoproteins E1 and E2. Based on crystal structures of component proteins and homology modeling, we constructed a nearly complete, pseudo-atomic model of the virus. Notably, this includes identification of the 33-residue cytoplasmic domain of E2 (cdE2), which follows a path from the E2 TM helix to the CP where it enters and exits the CP hydrophobic pocket and then folds back to contact the viral membrane. Modeling analysis identified three major contact regions between cdE2 and CP, and the roles of specific residues were probed by molecular genetics. This identified R393 and E395 of cdE2 and Y162 and K252 of CP as critical for virus assembly. The N-termini of the CPs form a contiguous network that interconnects 12 pentameric and 30 hexameric CP capsomers. A single glycoprotein spike cross-links three neighboring CP capsomers as might occur during initiation of virus budding.