Identification of amino acid residues critical for the B cell growth-promoting activity of HIV-1 matrix protein p17 variants

Background

HIV-1 matrix protein p17 variants (vp17s) detected in HIV-1-infected patients with non-Hodgkin's lymphoma (HIV-NHL) display, differently from the wild-type protein (refp17), B cell growth-promoting activity. Biophysical analysis revealed that vp17s are destabilized as compared to refp17, motivating us to explore structure-function relationships.

No evidence of inbreeding depression in fast declining herds of migratory caribou

Identifying inbreeding depression early in small and declining populations is essential for management and conservation decisions. Correlations between heterozygosity and fitness (HFCs) provide a way to identify inbreeding depression without prior knowledge of kinship among individuals. In Northern Quebec and Labrador, the size of two herds of migratory caribou (Rivière‐George, RG and Rivière‐aux‐Feuilles, RAF) has declined by one to two orders of magnitude in the last three decades. This raises the question of a possible increase in inbreeding depression originating from, and possibly contributing to, the demographic decline in those populations. Here, we tested for the association of genomic inbreeding indices (estimated with 22,073 SNPs) with body mass and survival in 400 caribou sampled in RG and RAF herds between 1996 and 2016. We found no association of individual heterozygosity or inbreeding coefficient with body mass or annual survival. Furthermore, those genomic inbreeding indices remained stable over the period monitored. These results suggest that the rapid and intense demographic decline of the herds did not cause inbreeding depression in those populations. Although we found no evidence for HFCs, if demographic decline continues, it is possible that such inbreeding depression would be triggered.     

脱氧雪腐镰刀菌烯醇对K~＋刺激的小麦根质膜ATP酶活性、K~＋吸收、外渗及再分配的影响

１０－８ｍｏｌ／Ｌ的ＤＯＮ毒素加入小麦根质膜制剂中可促进Ｋ＋刺激的ＡＴＰ酶活力,１０－６ｍｏｌ／Ｌ开始呈抑制效应,抑制程度随ＤＯＮ浓度加大而提高。根尖（５ｃｍ）离体根段于０．５ｍｍｏｌ／Ｌ的ＫＣｌ中,１０－８ｍｏｌ／Ｌ的ＤＯＮ能促进根段Ｋ＋吸收,１０－６ｍｏｌ／Ｌ以上浓度则Ｋ＋吸收呈抑制,１０－２ｍｏｌ／Ｌ浓度下根段的净吸收为负值,表明组织中Ｋ＋大量外渗。根段置蒸馏水中６ｈ,４ｍｍｏｌ／Ｌ的ＤＯＮ即导致振段Ｋ＋渗漏。用ＤＯＮ处理整株小麦根,浓度在０．２５ｍｍｏｌ／Ｌ以上可促进Ｋ＋从植株其它部位向根运输,而浓度在８ｍｍｏｌ／Ｌ时即抑制Ｋ＋向根富集,且根内Ｋ＋明显渗漏。     

Novel histone modifications in microglia derived from a mouse model of chronic pain

As the resident immune cells in the central nervous system, microglia play an important role in the maintenance of its homeostasis. Dysregulation of microglia has been associated with the development and maintenance of chronic pain. However, the relevant molecular pathways remain poorly defined. In this study, we used a mass spectrometry-based proteomic approach to screen potential changes of histone protein modifications in microglia isolated from the brain of control and cisplatin-induced neuropathic pain adult C57BL/6J male mice. We identified several novel microglial histone modifications associated with pain, including statistically significantly decreased histone H3.1 lysine 27 mono-methylation (H3.1K27me1, 54.8% of control) and H3 lysine 56 tri-methylation (7.5% of control), as well as a trend suggesting increased H3 tyrosine 41 nitration. We further investigated the functional role of H3.1K27me1 and found that treatment of cultured microglial cells for 4 consecutive days with 1–10 μM of NCDM-64, a potent and selective inhibitor of lysine demethylase 7A, an enzyme responsible for the demethylation of H3K27me1, dose-dependently elevated its levels with a greater than a two-fold increase observed at 10 μM compared to vehicle-treated control cells. Moreover, pretreatment of mice with NCDM-64 (10 or 25 mg/kg/day, i.p.) prior to cisplatin treatment prevented the development of neuropathic pain in mice. The identification of specific chromatin marks in microglia associated with chronic pain may yield critical insight into the contribution of microglia to the development and maintenance of pain, and opens new avenues for the development of novel nonopioid therapeutics for the effective management of chronic pain.     

Two closely linked tomato HKT coding genes are positional candidates for the major tomato QTL involved in Na+/K+ homeostasis

The location of major quantitative trait loci (QTL) contributing to stem and leaf [Na⁺] and [K⁺] was previously reported in chromosome 7 using two connected populations of recombinant inbred lines (RILs) of tomato. HKT1;1 and HKT1;2, two tomato Na⁺‐selective class I‐HKT transporters, were found to be closely linked, where the maximum logarithm of odds (LOD) score for these QTLs located. When a chromosome 7 linkage map based on 278 single‐nucleotide polymorphisms (SNPs) was used, the maximum LOD score position was only 35 kb from HKT1;1 and HKT1;2. Their expression patterns and phenotypic effects were further investigated in two near‐isogenic lines (NILs): 157‐14 (double homozygote for the cheesmaniae alleles) and 157‐17 (double homozygote for the lycopersicum alleles). The expression pattern for the HKT1;1 and HKT1;2 alleles was complex, possibly because of differences in their promoter sequences. High salinity had very little effect on root dry and fresh weight and consequently on the plant dry weight of NIL 157‐14 in comparison with 157‐17. A significant difference between NILs was also found for [K⁺] and the [Na⁺]/[K⁺] ratio in leaf and stem but not for [Na⁺] arising a disagreement with the corresponding RIL population. Their association with leaf [Na⁺] and salt tolerance in tomato is also discussed.     

The role of tumor necrosis factor-α for interleukin-10 production by murine dendritic cells

In the present study, we examined the role of tumor necrosis factor (TNF) in interleukin (IL)-10 production by dendritic cells (DCs) using bone-marrow derived DCs from wild type (WT) and TNF-α knockout (TNF-α^−/−) mice. Toll-like receptor (TLR) stimulation induced substantial level of IL-10 production by WT DCs, but significantly low level of IL-10 production by TNF-α^−/− DCs. In contrast, no significant difference was detected in IL-12 p40 production between WT and TNF-α^−/− DCs. Addition of TNF-α during TLR stimulation recovered the impaired ability of TNF-α^−/− DCs for IL-10 production. This recovery appeared to be associated with an activation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol 3-kinase/Akt following the TNF-α addition. Blocking these kinases significantly inhibited IL-10 production by TNF-α^−/− DCs stimulated with TLR ligands plus TNF-α. Thus, TNF-α may be a key molecule to regulate the balance between anti-inflammatory versus inflammatory cytokine production in DCs.     

Detection and validation of EST‐derived SNPs for poplar leaf rust Melampsora medusae f. sp. deltoidae

We report the discovery, characterization and validation of 118 single nucleotide polymorphisms (SNPs) for poplar leaf rust Melampsora medusae f. sp. deltoidae identified using a gene‐targeted approach in an expressed sequence tag (EST) library. We developed a genotyping assay using the iPLEX? primer extension method for two multiplex assays of 28 and 22 SNPs.     

至少6个突变基因型冬虫夏草菌在冬虫夏草子座中表达的动态变化

本研究检测了在冬虫夏草成熟过程中突变基因型冬虫夏草菌在子座中表达的动态变化。根据冬虫夏草菌基因内转录间隔区(ITS)序列中大量散在的点突变,设计了8个单核苷酸多态性(SNP)延伸引物,采用SNP质谱基因分型法测定各个SNP位点的单核苷酸延伸反应,观察冬虫夏草子座中转换突变和颠换突变基因型菌在冬虫夏草成熟过程中表达的动态变化。其中5个SNP延伸引物(067721-211,067721-240,067721-477,067721-531和067721-581)位于rDNA ITS1和ITS2段,用于区分GC和AT偏倚基因型,但不区分2个AT偏倚基因型。另外3个延伸引物(067740-324,067740-328和067740-360)位于rDNA 5.8S段,用于区分2个AT基因型。采用PCR+EcoRⅠ限制性酶切法检验2个GC偏倚基因型冬虫夏草菌在冬虫夏草成熟过程中表达的动态变化。结果表明:冬虫夏草子座rDNA ITS1-5.8S-ITS2片段的8个SNP位点的质谱图谱显示冬虫夏草子座中存在至少5个冬虫夏草菌转换突变和颠换突变等位基因。它们的表达在冬虫夏草成熟过程中呈现动态变化。067721-211和067721-477位点的AT偏倚型等位基因的峰高明显高于GC偏倚型;随着冬虫夏草的成熟,这2个位点的AT型等位基因峰高大幅度下降。SNP质谱图不仅显示转换突变的等位基因,颠换突变等位基因也有很高的检出率,它们的峰高在一些位点甚至超过GC和AT基因型等位基因;随着冬虫夏草的成熟,颠换突变等位基因的检出率和峰高趋于下降。在区分2个AT偏倚基因型的研究中,AB067744和AB067740 2个基因型的等位基因同时存在于未成熟冬虫夏草子座中。随着冬虫夏草的成熟,AB067744基因型等位基因的峰高明显降低,而AB067740基因型等位基因的峰高明显升高。PCR产物EcoRⅠ酶切试验发现子座中存在2组GC偏倚型菌,具有完全不同的成熟模式。综上,冬虫夏草子座中存在至少6个突变基因型冬虫夏草菌,其表达随着冬虫夏草的成熟呈现动态变化。这些突变基因型菌表达的动态变化对于冬虫夏草子座的萌发和成熟具有重要菌物学意义。     

低氧及酸化胁迫对大黄鱼幼鱼离子调节与鳃组织结构的影响

为探讨大黄鱼幼鱼在低氧及酸化胁迫下机体离子调节情况,本研究探讨了低氧(溶解氧量DO 3.5 mg·L-1,pH 8.1)、酸化(DO 7.0 mg·L-1,pH 7.35)以及低氧酸化协同胁迫(DO3.5 mg·L-1,pH 7.35)对大黄鱼幼鱼鳃组织结构以及离子调节相关生理指标的影响.结果 表明:低氧胁迫下,大黄鱼...     

A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet–Biedl syndrome in a Pakistani family

Bardet–Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet–Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet–Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet–Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease. Homozygous regions obtained from SNP array depicted three known genes BBS10, BBS14 and BBS2. Bidirectional sequencing of all coding exons by traditional sequencing of all these three genes showed a homozygous deletion of 10 nucleotides (c.1958_1967del), in BBS10 in both affected brothers. The segregation analysis revealed that the parents, paternal grandfather, maternal grandmother and an unaffected sister were heterozygous for the deletion. Such a large deletion in BBS10 has not been reported previously in any population and is likely to be contributing to the phenotype of Bardet–Biedl Syndrome in this family.