A novel liver specific isoform of the rat LAR transcript is expressed as a truncated isoform encoded from a 5'UTR located within intron 11

Background  

The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage.     

哈尔滨西郊赤狐冬季巢区的初步研究

本文利用雪地跟踪方法对哈尔滨西郊5只赤狐在1985-1986年冬季的巢区做了观察。结果表明,5只狐对巢区内各部分使用的强度是不等的,对巢区中部的某些地块使用强度要高于对外围的使用,并具有明显的方向性。5个巢区的平均活动半径为320±68米至557±82米,面积为1.44-4.O9平方公里,线性指数为1.079至2。5只狐相邻距离约1000米。     

Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns

Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS₁₀) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10⁻¹¹; N = 467). A higher GRS₁₀ was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS₁₀ and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation.     

Two distinct conformational states define the interaction of human RAD51‐ATP with single‐stranded DNA

An essential mechanism for repairing DNA double‐strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein filament on single‐stranded DNA, promoting DNA‐strand exchange. Here, we study the interaction of hRAD51 with single‐stranded DNA using a single‐molecule approach. We show that ATP‐bound hRAD51 filaments can exist in two different states with different contour lengths and with a free‐energy difference of ~4 k_BT per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly‐competent ADP‐bound configuration. In agreement with the single‐molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51‐ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51‐ATP filaments can exist in two interconvertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange.     

Nonglucosylated oligosaccharides are transferred to protein in MI8-5 Chinese hamster ovary cells

A CHO mutant MI8-5 was found to synthesize Man9-GlcNAc2-P-P-dolichol rather than Glc3Man9GlcNAc2-P-P-dolichol as the oligosaccharide-lipid intermediate in N-glycosylation of proteins. MI8-5 cells were incubated with labeled mevalonate, and the prenol was found to be dolichol. The mannose-labeled oligosaccharide released from oligosaccharide-lipid of MI8-5 cells was analyzed by HPLC and alpha-mannosidase treatment, and the data were consistent with a structure of Man9GlcNAc2. In addition, MI8-5 cells did not incorporate radioactivity into oligosaccharide- lipid during an incubation with tritiated galactose, again consistent with MI8-5 cells synthesizing an unglucosylated oligosaccharide-lipid. MI8-5 cells had parental levels of glucosylphosphoryldolichol synthase activity. However, in two different assays, MI8-5 cells lacked dolichol- P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase activity. MI8-5 cells were found to synthesize glucosylated oligosaccharide after they were transfected with Saccharomyces cerevisiae ALG 6, the gene for dolichol-P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase. MI8-5 cells were found to incorporate mannose into protein 2-fold slower than parental cells and to approximately a 2-fold lesser extent.      

Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution

The fetal globin genes G gamma and A gamma from one chromosome of a chimpanzee (Pan troglodytes) were sequenced and found to be closely similar to the corresponding genes of man and the gorilla. These genes contain identical promoter and termination signals and have exons 1 and 2 separated by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G gamma and A gamma, respectively). Each intron 2 has a stretch of simple sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The two chimpanzee genes encode polypeptide chains that differ only at position 136 (glycine in G gamma and alanine in A gamma) and that are identical to the corresponding human chains, which have aspartic acid at position 73 and lysine at 104 in contrast to glycine and arginine at these respective positions of the gorilla A gamma chain. Phylogenetic analysis by the parsimony method revealed four silent (synonymous) base substitutions in evolutionary descent of the chimpanzee G gamma and A gamma codons and none in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla) coding sequences evolved at one-tenth the average mammalian rate for nonsynonymous and one-fourth that for synonymous substitutions. Three sequence regions that were affected by gene conversions between chimpanzee G gamma and A gamma loci were identified: one extended 3' of the hot spot with G gamma replaced by the A gamma sequence, another extended 5' of the hot spot with A gamma replaced by G gamma, and the third conversion extended from the 5' flanking to the 5' end of intron 2, with G gamma replaced here by the A gamma sequence. A conversion similar to this third one has occurred independently in the descent of the gorilla genes. The four previously identified conversions, labeled C1-C4 (Scott et al. 1984), were substantiated with the addition of the chimpanzee genes to our analysis (C1 being shared by all three hominines and C2, C3, and C4 being found only in humans). Thus, the fetal genes from all three of these hominine species have been active in gene conversions during the descent of each species.