Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons

Hippocampal GABAergic interneurons are crucial for cortical network function and have been implicated in psychiatric disorders. We show here that Neuregulin 3 (Nrg3), a relatively little investigated low‐affinity ligand, is a functionally dominant interaction partner of ErbB4 in parvalbumin‐positive (PV) interneurons. Nrg3 and ErbB4 are located pre‐ and postsynaptically, respectively, in excitatory synapses on PV interneurons in vivo. Additionally, we show that ablation of Nrg3 results in a similar phenotype as the one described for ErbB4 ablation, including reduced excitatory synapse numbers on PV interneurons, altered short‐term plasticity, and disinhibition of the hippocampal network. In culture, presynaptic Nrg3 increases excitatory synapse numbers on ErbB4⁺ interneurons and affects short‐term plasticity. Nrg3 mutant neurons are poor donors of presynaptic terminals in the presence of competing neurons that produce recombinant Nrg3, and this bias requires postsynaptic ErbB4 but not ErbB4 kinase activity. Furthermore, when presented by non‐neuronal cells, Nrg3 induces postsynaptic membrane specialization. Our data indicate that Nrg3 provides adhesive cues that facilitate excitatory neurons to synapse onto ErbB4⁺ interneurons.     

mIL21-SA双功能融合蛋白锚定治疗膀胱癌实验研究

目的:制备链亲合素标记的鼠白细胞介素21融合蛋白(mIL21-SA),治疗小鼠表浅膀胱癌。方法:构建mIL21-SA-pET21质粒,BL21表达,Ni-NTA纯化,透析复性,Western blot鉴定,MTT法检测其对小鼠胸腺细胞的增殖作用,流式检测其对生物素化的MB49锚定修饰率。建立小鼠MB49表浅膀胱癌模型,将mIL21-SA锚定在小鼠膀胱表面进行治疗并观察小鼠存活时间。60d后对mIL21-SA治疗后存活小鼠进行二次攻击。结果:mIL21-SA可以促进T细胞增殖,且具有SA介导的高效结合已生物素化的MB49表面的功能(修饰率98.74%)。膀胱灌注60d后,mIL21-SA组有10只(10/25)存活,二次攻击后,仍有6只(6/10)存活。与对照组比较均有统计学意义(P<0.05)。结论:该实验研制了具有双重活性的mIL21-SA,mIL21-SA锚定修饰治疗表浅膀胱癌是一种有效的免疫治疗方法。     

Visual stabilization of the eyes in primates

Observers moving through a texture three-dimensional world experience potentially confusing patterns of optic flow. Recent experiments on monkeys and humans have revealed the existence of rapid, yet cortically mediated, reflex eye movements that automatically single out images in the plane of fixation for stabilization and ignore images that are nearer or further.     

Two new cytotypes reinforce that <Emphasis Type="Italic">Micronycteris hirsuta</Emphasis> Peters, 1869 does not represent a monotypic taxon

Background

The genus Micronycteris is a diverse group of phyllostomid bats currently comprising 11 species, with diploid number (2n) ranging from 26 to 40 chromosomes. The karyotypic relationships within Micronycteris and between Micronycteris and other phyllostomids remain poorly understood. The karyotype of Micronycteris hirsuta is of particular interest: three different diploid numbers were reported for this species in South and Central Americas with 2n?=?26, 28 and 30 chromosomes. Although current evidence suggests some geographic differentiation among populations of M. hirsuta based on chromosomal, morphological, and nuclear and mitochondrial DNA markers, the recognition of new species or subspecies has been avoided due to the need for additional data, mainly chromosomal data.

Results

We describe two new cytotypes for Micronycteris hirsuta (MHI) (2n?=?26 and 25, NF?=?32), whose differences in diploid number are interpreted as the products of Robertsonian rearrangements. C-banding revealed a small amount of constitutive heterochromatin at the centromere and the NOR was located in the interstitial portion of the short arm of a second pair, confirmed by FISH. Telomeric probes hybridized to the centromeric regions and weakly to telomeric regions of most chromosomes. The G-banding analysis and chromosome painting with whole chromosome probes from Carollia brevicauda (CBR) and Phyllostomus hastatus (PHA) enabled the establishment of genome-wide homologies between MHI, CBR and PHA.

Conclusions

The karyotypes of Brazilian specimens of Micronycteris hirsuta described here are new to Micronycteris and reinforce that M. hirsuta does not represent a monotypic taxon. Our results corroborate the hypothesis of karyotypic megaevolution within Micronycteris, and strong evidence for this is that the entire chromosome complement of M. hirsuta was shown to be derivative with respect to species compared in this study.

     

Conditional and unconditional QTL mapping of drought-tolerance-related traits of wheat seedling using two related RIL populations

For discovering the quantitative trait loci (QTLs) contributing to early seedling growth and drought tolerance during germination, conditional and unconditional analyses of 12 traits of wheat seedlings: coleoptile length, seedling height, longest root length, root number, seedling fresh weight, stem and leaves fresh weight, root fresh weight, seedling dry weight, stem and leaves dry weight, root dry weight, root to shoot fresh weight ratio, root-to-shoot dry weight ratio, were conducted under two water conditions using two F_8:9 recombinant inbred line (RIL) populations. The results of unconditional analysis are as follows: 88 QTLs accounting for 3.33–77.01% of the phenotypic variations were detected on chromosomes 1A, 1B, 1D, 2A, 2B, 2D, 3A, 3B, 4A, 4B, 4D, 5A, 5B, 5D, 6A, 6B, 6D, 7A, 7B and 7D. Among these QTLs, 19 were main-effect QTLs with a contribution rate greater than 10%. The results of the conditional QTL analysis of 12 traits under osmotic stress on normal water conditions were as follows: altogether 22 QTLs concerned with drought tolerance were detected on chromosomes 1B, 2A, 2B, 3B, 4A, 5D, 6A, 6D, 7B, and 7D. Of these QTLs, six were main-effect QTLs. These 22 QTLs were all special loci directly concerned with drought tolerance and most of them could not be detected by unconditional analysis. The finding of these QTLs has an important significance for fine-mapping technique, map-based cloning, and molecular marker-assisted selection of early seedling traits, such as growth and drought tolerance.     

Wheat kernel dimensions: how do they contribute to kernel weight at an individual QTL level?

Kernel dimensions (KD) contribute greatly to thousand-kernel weight (TKW) in wheat. In the present study, quantitative trait loci (QTL) for TKW, kernel length (KL), kernel width (KW) and kernel diameter ratio (KDR) were detected by both conditional and unconditional QTL mapping methods. Two related F(8:9) recombinant inbred line (RIL) populations, comprising 485 and 229 lines, respectively, were used in this study, and the trait phenotypes were evaluated in four environments. Unconditional QTL mapping analysis detected 77 additive QTL for four traits in two populations. Of these, 24 QTL were verified in at least three trials, and five of them were major QTL, thus being of great value for marker assisted selection in breeding programmes. Conditional QTL mapping analysis, compared with unconditional QTL mapping analysis, resulted in reduction in the number of QTL for TKW due to the elimination of TKW variations caused by its conditional traits; based on which we first dissected genetic control system involved in the synthetic process between TKW and KD at an individual QTL level. Results indicated that, at the QTL level, KW had the strongest influence on TKW, followed by KL, and KDR had the lowest level contribution to TKW. In addition, the present study proved that it is not all-inclusive to determine genetic relationships of a pairwise QTL for two related/causal traits based on whether they were co-located. Thus, conditional QTL mapping method should be used to evaluate possible genetic relationships of two related/causal traits.     

新生隐球菌转录共激活因子MBF1基因的鉴定与敲除

目的构建新生隐球菌转录共激活因子MBF1基因缺陷菌株。方法采用套叠PCR方法 ,构建含有抗性基因NEO以及靶基因上下游同源DNA片段的基因敲除框,通过基因枪将重组片段转化入新生隐球菌,应用PCR筛选和DNA序列测序方法对基因突变株进行鉴定与验证。结果成功构建了新生隐球菌基因突变株mbf1裣。结论通过基因突变株mbf1裣的构建,为深入研究新生隐球菌转录辅助因子Mbf1的功能机制奠定基础。     

SIRAC: Supervised Identification of Regions of Aberration in aCGH datasets

Background  

Array comparative genome hybridization (aCGH) provides information about genomic aberrations. Alterations in the DNA copy number may cause the cell to malfunction, leading to cancer. Therefore, the identification of DNA amplifications or deletions across tumors may reveal key genes involved in cancer and improve our understanding of the underlying biological processes associated with the disease.     

Nitric oxide-dependent inhibition of alveolar fluid clearance in hydrostatic lung edema

Formation of cardiogenic pulmonary edema in acute left heart failure is traditionally attributed to increased fluid filtration from pulmonary capillaries and subsequent alveolar flooding. Here, we demonstrate that hydrostatic edema formation at moderately elevated vascular pressures is predominantly caused by an inhibition of alveolar fluid reabsorption, which is mediated by endothelial-derived nitric oxide (NO). In isolated rat lungs, we quantified fluid fluxes into and out of the alveolar space and endothelial NO production by a two-compartmental double-indicator dilution technique and in situ fluorescence imaging, respectively. Elevation of hydrostatic pressure induced Ca(2+)-dependent endothelial NO production and caused a net fluid shift into the alveolar space, which was predominantly attributable to impaired fluid reabsorption. Inhibition of NO production or soluble guanylate cyclase reconstituted alveolar fluid reabsorption, whereas fluid clearance was blocked by exogenous NO donors or cGMP analogs. In isolated mouse lungs, hydrostatic edema formation was attenuated by NO synthase inhibition. Similarly, edema formation was decreased in isolated mouse lungs of endothelial NO synthase-deficient mice. Chronic heart failure results in endothelial dysfunction and preservation of alveolar fluid reabsorption. These findings identify impaired alveolar fluid clearance as an important mechanism in the pathogenesis of hydrostatic lung edema. This effect is mediated by endothelial-derived NO acting as an intercompartmental signaling molecule at the alveolo-capillary barrier.     

Mitochondrial DNA sequence variation in the spruce budworm species complex (Choristoneura: Lepidoptera)

A combination of polymerase-chain-reaction amplification and automated DNA sequencing was used to survey variation in a species complex of pest insects, the spruce budworms (Choristoneura fumiferana species group), and an outgroup species, C. rosaceana. We sequenced an mtDNA region of 1,573 bp that extends from the middle of cytochrome oxidase subunit I (COI) through tRNA leucine (UUR) to the end of cytochrome oxidase subunit II. In addition, we examined levels of intraspecific variation within a 470-bp region of the COI gene. Choristoneura fumiferana clearly represented the oldest lineage within its species group, with 2.7%-2.9% sequence divergence from the other species. In contrast, the four remaining species (C. pinus, C. biennis, C. occidentalis, and C. orae) had closely related or identical mtDNA, with < 1% divergence among most of their haplotypes. Despite its older lineage and widespread geographic distribution, C. fumiferana showed significantly lower intraspecific genetic diversity than did C. occidentalis. Choristoneura orae shared haplotypes with C. occidentalis and C. biennis, and species-level separation of these three species was not supported. Two divergent, uncommon haplotypes were also found in C. occidentalis and C. biennis. The divergent haplotype in C. biennis had an unusually high number of inferred amino acid replacements, suggesting selective differences between mitochondrial DNA haplotypes. Transition:transversion ratios in Choristoneura paralleled those found in Drosophila; transition:transversion ratios were highest in closely related sequences but decreased with increasing sequence divergence. Nucleotide composition showed an A+T bias that was near the high end of the range known for insects. This work illustrates the potential utility of direct DNA sequencing in assessing population structures, species limits, and phylogenetic relationships among organisms that have not previously been subjected to DNA analysis.