Microtubule-associated protein 1B (MAP1B) is required for dendritic spine development and synaptic maturation

Microtubule-associated protein 1B (MAP1B) is prominently expressed during early stages of neuronal development, and it has been implicated in axonal growth and guidance. MAP1B expression is also found in the adult brain in areas of significant synaptic plasticity. Here, we demonstrate that MAP1B is present in dendritic spines, and we describe a decrease in the density of mature dendritic spines in neurons of MAP1B-deficient mice that was accompanied by an increase in the number of immature filopodia-like protrusions. Although these neurons exhibited normal passive membrane properties and action potential firing, AMPA receptor-mediated synaptic currents were significantly diminished. Moreover, we observed a significant decrease in Rac1 activity and an increase in RhoA activity in the post-synaptic densities of adult MAP1B(+/-) mice when compared with wild type controls. MAP1B(+/-) fractions also exhibited a decrease in phosphorylated cofilin. Taken together, these results indicate a new and important role for MAP1B in the formation and maturation of dendritic spines, possibly through the regulation of the actin cytoskeleton. This activity of MAP1B could contribute to the regulation of synaptic activity and plasticity in the adult brain.     

Functional and structural impact of pirfenidone on the alterations of cardiac disease and diabetes mellitus

A synthetic compound, termed pirfenidone (PFD), is considered promising for the treatment of cardiac disease. It leads to beneficial effects in animal models of diabetes mellitus (DM); as well as in heart attack, atrial fibrillation, muscular dystrophy, and diabetic cardiomyopathy (DC). The latter is a result of alterations linked to metabolic syndrome as they promote cardiac hypertrophy, fibrosis and contractile dysfunction. Although reduced level of fibrosis and stiffness represent an essential step in the mechanism of PFD action, a wide range of functional effects might also contribute to the therapeutic benefits. For example, PFD stimulates L-type voltage-gated Ca²⁺ channels (LTCCs), which are pivotal for a process known as excitation–contraction coupling (ECC). Recent evidence suggests that these two types of actions – namely structural and functional – aid in treating both cardiac disease and DM. This view is supported by the fact that in DC, for example, systolic dysfunction arises from both cardiac stiffness linked to fibrosis and down-regulation of ECC. Thus, not surprisingly, clinical trials have been conducted with PFD in the settings of DM, for treating not only cardiac but also renal disease. This review presents all these concepts, along with the possible mechanisms and pathophysiological consequences.     

5-HT_(1A)受体参与学习记忆的分子机制研究进展

5-HT(五羟色胺)能神经元是起源最早的神经元之一,在传统的神经元形成前,成长中的轴突就可释放5-HT,并且通过5-HT的各种亚型受体来实现不同的功能。近年来,随着5-HT、5-HTRs(五羟色胺受体)的基因克隆及5-HT受体选择性激动剂和拮抗剂的研究发展,5-HT系统在学习记忆中的作用越发明确,许多研究结果表明:5-HT系统在记忆的巩固、短时程记忆(STM)及长时程记忆(LTM)中起重要作用,5-HT1A受体更是在非脊椎动物及哺乳动物的脑中都高度表达,并通过相似的信号转导途径参与学习与记忆的形成和巩固。本文将介绍5-HT1A受体、5-HT1A受体激动剂、5-HT1A受体拮抗剂及其与学习记忆的联系,重点综述5-HT1A受体参与学习记忆的信号转导途径研究进展,讨论5-HT1A受体参与学习记忆的可能性分子神经生物学机制。     

脂肪细胞因子 CTRP4转基因鼠的构建与鉴定

目的：建立人CTRP4基因的转基因小鼠,为脂肪细胞因子CTRP4的体内功能研究奠定基础。方法首先构建人CTRP4的转基因小鼠线性化表达载体,再利用显微注射的方法将载体注射入小鼠受精卵,从而构建人CTRP4的首建鼠（ Founder ）并与野生型小鼠交配繁殖得到F1代阳性小鼠,再通过近亲繁殖与测交的方法,得到CTRP4转基因纯合子小鼠,并通过PCR和western blot 的方法对纯合子小鼠进行鉴定。结果得到人CTRP4转基因小鼠纯合子小鼠两个品系,western blot鉴定该转基因小鼠心脏,肝脏,脑,肾脏等多种组织中均呈现CTRP4高表达。结论成功构建了人CTRP4转基因小鼠纯合子小鼠。     

Multilocus phylogeography of the Patagonian lizard complex Liolaemus kriegi (Iguania: Liolaemini)

This study presents a detailed phylogeographical analysis of one of the most conspicuous groups of lizards in northwestern Patagonia, the Liolaemus kriegi complex. This region is geographically very complex as a result of Andean orogeny and subsequent volcanism coupled with a long history of glaciations and climatic changes. For 247 individuals we sequenced one mitochondrial gene (cytochrome b) and for a subset we sequenced another mitochondrial gene [12S ribosomal RNA (12S)] and two nuclear fragments [kinesin family member 24 (KIF24) and BA3 ribosomal RNA (BA3)]. We obtained gene trees and mitochondrial and nuclear haploytpe networks, and estimated genetic distances between the main lineages and basic molecular diversity indices. We also performed spatial analysis of molecular variance (SAMOVA) and Bayesian Skyline Plot (BSP) analyses, and concordant patterns from different lines of evidence permitted delimitation of seven lineages: two described species, Liolaemus buergeri and Liolaemus tregenzai; four candidate species, Liolaemus sp. A, Liolaemus sp. B, Liolaemus sp. C, and Liolaemus sp. D; and one lineage that includes all individuals from the geographical range of Liolaemus ceii and L. kriegi, referred to as L. kriegi + L. ceii. We discuss the evolutionary processes that may contribute to the origin of these lineages and their taxonomic and conservation implications. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 113 , 256–269.     

Initial studies with high resolution TEM and electron energy loss spectroscopy studies of ferritin cores extracted from brains of patients with progressive supranuclear palsy and Alzheimer disease.

Studies of crystallographic structure and composition of core nanocrystals of ferritin bound to aberrant tau filaments extracted from progressive supranuclear Palsy (PSP) and Alzheimer disease (AD) brain tissues were performed using high resolution transmission electron microscopy (HRTEM) and electron energy loss spectroscopy (EELS). The results were compared with those obtained from synthetic Fe3O4 crystal (magnetite) and horse spleen ferritin cores. Core dimensions of ferritin molecules from PSP and AD were similar to those found in normal brain. Ferritin cores nanocrystals in AD seems to have less ordered structure than in PSP. Some nanocrystals did not have the hexagonal ferrihydrite structure generally found in healthy ferritin but rather a cubic structure similar to magnetite, a crystalline form in which both Fe2+ and Fe3+ are present. The presence of ferrous ion, Fe2+, may indicate some dysfunction in these pathological ferritins that might contribute to production of free radicals via the Fenton reaction involved in neurodegeneration.     

内蒙古草原人类福祉与生态系统服务及其动态变化——以锡林郭勒草原为例

以锡林郭勒盟为研究区域,建立人类福祉评价指标体系,通过牧户问卷调查了解牧户对草原生态系统服务和福祉变化的认识,结合当地的自然环境、生态环境和社会经济等多方面的多年统计数据,采用专家打分法对牧民各福祉指标打分,对2001年和2010年牧民福祉变化进行了评估和分析。结果表明:收入、道路覆盖率、农村合作医疗保险和文化教育方面对牧民福祉变化贡献最大;生产资料持续供给能力下降是导致收入减少的主要方面;旗县的犯罪率,环境空气质量,饮食结构,离婚率等是导致牧民福祉下降的主要方面。有关研究结果为提高锡林郭勒盟人类福祉、生态保护和区域可持续发展政策制定提供科学依据。     

Paracoccidioidomycosis in people living with HIV/AIDS: A historical retrospective cohort study in a national reference center for infectious diseases,Rio de Janeiro,Brazil

Paracoccidioidomycosis (PCM) is one of the main endemic systemic mycoses in Latin America, usually occurring in rural areas. When PCM occurs simultaneously with underlying immunosuppressive conditions, it can present as an opportunistic disease. Between 2000 and 2017, literature reported around 200 PCM cases in people living with HIV/AIDS (PLWHA). To address research gaps on this co-infection and to study its possible temporal changes in the last decade, we performed an active co-infection case search on the HIV/AIDS and PCM cohorts from a Brazilian reference center database from 1989 to 2019. We found 20 PLWHA among 684 PCM patients (2.92%), predominantly male (70.0%) and urban workers (80.0%). The median age of patients was higher in the 2010–2019 decade (p = 0.006). The occurrence of PCM in PLWHA was lower when compared with other fungal diseases. Although 50.0% of the patients had already been diagnosed with HIV infection and presented CD4+ T cell counts greater than 200/mm³ at the time of PCM diagnosis, the suspicion of immunosuppression in the context of atypical and more severe clinical forms of PCM revealed the diagnosis of HIV infection in 35.0% of the patients. Two (10.0%) patients had an evolution compatible with immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy (ART).We highlight the importance of considering a PCM diagnosis in PLWHA to prevent a late-onset treatment and progression to severe manifestations and unfavorable outcomes. In addition, HIV investigation is recommended in PCM patients, especially those with atypical and more severe clinical presentations.     

若尔盖人-狼冲突现状与管理研究

大中型食肉动物肇事事件导致人类与野生动物关系恶化,给生物多样性保护工作带来巨大的挑战。若尔盖湿地是我国三大湿地之一,湿地、草原分布广泛,生物多样性丰富,畜牧业发达,但近年来狼(Canis lupus)捕杀牲畜的肇事事件时有发生。为了解若尔盖野生狼肇事件的空间分布以及牧民对人-狼冲突管理的看法,本研究于2022年对若尔盖县13个乡镇83个行政村进行走访调查。结果表明：(1)多数受访者(66.0%)认为在过去5年内,若尔盖县野生狼数量有所增加;(2)狼肇事事件具有明显的空间分异性,最严重的是包座乡。包座乡临近山区,该区域牧场面积广阔、牧民饲养牲畜数量多等原因导致该镇发生狼肇事事件较多;(3)对于狼肇事,绝大多数牧民(85.0%)更希望采取经济补偿或者驱赶措施,只有少数牧民(9.4%)希望采取捕杀的措施;(4)影响牧民对狼肇事管理措施的偏好因子中,受教育程度、年龄、民族以及被杀牲畜数量有显著影响。建议加强狼种群监测管理,采取措施减少狼捕杀牲畜,优化补偿机制,缓解当地牧民与狼之间的矛盾。本研究为当前若尔盖县野生动物保护和管理决策提供了依据,对其他地区大型食肉动物与当地居民冲突管理具有借鉴意义。     

The removal of the carboxy-terminal region of tubulin favors its vinblastine-induced aggregation into spiral-like structures

Vinblastine induces brain tubulin to assemble into spirals. This process is stimulated by microtubule-associated proteins (MAPs) which copolymerize with brain microtubules assembled in vitro. When the carboxy terminal of tubulin is removed by subtilisin digestion, vinblastine readily induces the aggregation of tubulin into spiral-like or circular structures, even in the absence of MAPs. These results suggest that in the absence of MAPs, the carboxy-terminal domain of tubulin may inhibit vinblastine-induced polymerization of tubulin into spiral-like structures.