Neural coding of action in three dimensions: Task- and time-invariant reference frames for visuospatial and motor-related activity in parietal area V6A

Goal-directed movements involve a series of neural computations that compare the sensory representations of goal location and effector position, and transform these into motor commands. Neurons in posterior parietal cortex (PPC) control several effectors (e.g., eye, hand, foot) and encode goal location in a variety of spatial coordinate systems, including those anchored to gaze direction, and to the positions of the head, shoulder, or hand. However, there is little evidence on whether reference frames depend also on the effector and/or type of motor response. We addressed this issue in macaque PPC area V6A, where previous reports using a fixate-to-reach in depth task, from different starting arm positions, indicated that most units use mixed body/hand-centered coordinates. Here, we applied singular value decomposition and gradient analyses to characterize the reference frames in V6A while the animals, instead of arm reaching, performed a nonspatial motor response (hand lift). We found that most neurons used mixed body/hand coordinates, instead of “pure” body-, or hand-centered coordinates. During the task progress the effect of hand position on activity became stronger compared to target location. Activity consistent with body-centered coding was present only in a subset of neurons active early in the task. Applying the same analyses to a population of V6A neurons recorded during the fixate-to-reach task yielded similar results. These findings suggest that V6A neurons use consistent reference frames between spatial and nonspatial motor responses, a functional property that may allow the integration of spatial awareness and movement control.     

Human T-Cell Leukemia Virus Type 1 Envelope Protein: Post-Entry Roles in Viral Pathogenesis

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and fatal CD4⁺ T-cell malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neurological disease. Disease progression in infected individuals is the result of HTLV-1-driven clonal expansion of CD4⁺ T-cells and is generally associated with the activities of the viral oncoproteins Tax and Hbz. A closely related virus, HTLV-2, exhibits similar genomic features and the capacity to transform T-cells, but is non-pathogenic. In vitro, HTLV-1 primarily immortalizes or transforms CD4⁺ T-cells, while HTLV-2 displays a transformation tropism for CD8⁺ T-cells. This distinct tropism is recapitulated in infected people. Through comparative studies, the genetic determinant for this divergent tropism of HTLV-1/2 has been mapped to the viral envelope (Env). In this review, we explore the emerging roles for Env beyond initial viral entry and examine current perspectives on its contributions to HTLV-1-mediated disease development.     

mCD99L2基因沉默对小鼠B淋巴瘤细胞系A20细胞转化为 H/RS样细胞的影响

目的探究mCD99L2基因沉默对小鼠B淋巴瘤细胞系A20细胞转化为H/RS样细胞的影响。方法重组SiRNA表达质粒LV-mCD99L2,体外转染内源性mCD99L2表达阳性的A20细胞,筛选出稳定表达LV质粒的细胞株并扩增培养;采用免疫荧光技术和流式细胞仪检测转化前后两组细胞鼠源CD30表达;透射电镜观察转化后细胞超微结构的形态特点;细胞计数方法动态观测培养细胞干扰组A20-LV-mCD99L2和未经干扰组A20细胞的H/RS样细胞(直径≥25μm)转型率,以人霍奇金淋巴瘤细胞系L428作为对照;采用流式细胞仪检测细胞周期变化。结果获得了稳定表达LV质粒的单克隆细胞株A20-LV-mCD99L2;免疫荧光标记显示转化细胞CD30( );流式细胞仪检测A20-LV-mCD99L2细胞CD30阳性率为54.4%;透射电镜观察转化后细胞核增大,可见单核、双核及多核,核仁明显的H/RS样细胞;干扰组H/RS样细胞的转型率明显高于未经干扰组(P<0.01)。两组处于S期的细胞无明显差异,两组细胞均未见凋亡峰。结论mCD99L2基因沉默可诱导小鼠B淋巴瘤细胞系A20细胞转化为H/RS样细胞。     

脑梗死后出血性转化的研究进展

本文综述了脑梗死后出血性转化的类型和预后以及可能的机制,并讨论了溶栓剂组织型纤溶酶原激活物(t-PA)对脑梗死后出血性转化的影响以及出血性转化的干预措施,为脑梗死的临床治疗和研究提供参考。     

CT微血管表面通透性参数在检测缺血性脑卒中出血性转化中的应用

目的探讨CT灌注(CT perfusion,CTP)成像获得的脑组织局部微血管表面通透性(permeability surface,PS)参数在预测急性缺血性脑卒中后出血性转化中的应用价值。方法回顾性分析发病3~8h内急性缺血性脑卒中患者的影像学资料,所有患者均进行CTP检查。根据随访CT或MRI影像判断有无发生出血性转化(hemorrhagic transforma-tion,HT),分为出血组(PSHT)及未出血组(PSNo-HT)。采用Mann-Whitney U检验比较PSHT及PSNo-HT两者相应临床及影像学参数之间的差异。采用受试者工作曲线(receiver operating characteristic,ROC)分析相对表面通透性(rPS)值预测HT的敏感度及特异性。结果 26例患者进行入院CTP检查的患者中11例发生HT。PSHT组与PSNo-HT组患者的rPS值之间差异有统计学意义(P<0.05),两组患者的年龄、发病时间、rCBV及rCBF的差异无统计学意义(P值均>0.05)。ROC分析显示:rPS阈值为5.81时,预测HT的敏感性及特异性分别为90.91%、87.50%。结论动态CTP成像获得的PS参数图能够判断哪些患者易发生HT,在指导急性缺血性脑卒中患者的临床治疗方面有较高的应用价值。     

人胚胎发育过程中间充质干祖细胞与造血细胞间的起源关系探讨

目的探讨人胚胎发育过程中间充质干祖细胞(MSPCs)与造血细胞间的起源关系。方法取发育不同时间药流胚胎,分离不同造血组织消化成单个细胞,于高增殖潜能集落形成细胞(HPP-CFC)培养体系培养10~14 d,倒置显微镜下挑取直径大于0.5 mm的HPP-CFC集落于液体培养体系进行二次培养,对二次培养中出现的贴壁细胞进行扩增并鉴定其细胞表面分子的表达,于不同分化体系鉴定其是否具有MSPCs的分化特性。结果本研究总结了胚胎发育不同时期主动脉-性腺-中肾(AGM)区、卵黄囊、胎肝等不同部位包括HPP-CFC在内的各类造血前体细胞的发育动态,发现从28体节开始,一定比例的AGM区HPP-CFC除能够分化产生造血细胞外,其来源的贴壁细胞具有MSPCs的分化功能,贴壁细胞在淋巴母细胞转化实验中可抑制T细胞的增殖。结论人胚胎AGM区内,部分MSPCs和造血细胞起源于共同前体。     

The dual role of martensitic transformation in fatigue crack growth

Deformation-induced martensitic transformation (DIMT) has been used for designing high-performance alloys to prevent structural failure under static loads. Its effectiveness against fatigue, however, is unclear. This limits the application of DIMT for parts that are exposed to variable loads, although such scenarios are the rule and not the exception for structural failure. Here we reveal the dual role of DIMT in fatigue crack growth through in situ observations. Two antagonistic fatigue mechanisms mediated by DIMT are identified, namely, transformation-mediated crack arresting, which prevents crack growth, and transformation-mediated crack coalescence, which promotes crack growth. Both mechanisms are due to the hardness and brittleness of martensite as a transformation product, rather than to the actual transformation process itself. In fatigue crack growth, the prevalence of one mechanism over the other critically depends on the crack size and the mechanical stability of the parent austenite phase. Elucidating the two mechanisms and their interplay allows for the microstructure design and safe use of metastable alloys that experience fatigue loads. The findings also generally reveal how metastable alloy microstructures must be designed for materials to be fatigue-resistant.

Deformation-induced martensitic transformation (DIMT) (1, 2) has been used as an effective strengthening mechanism to design strong and ductile alloys for engineering applications. For instance, the use of the transformation-induced plasticity (TRIP) effect (3, 4) to overcome the strength–ductility trade-off (5) has enabled many high-performance alloys, such as advanced steels (6, 7), titanium alloys (8), and high-entropy alloys (9). Yet, such design concepts are based on the assumption of flaw-free alloys subjected to static loads. However, the damage tolerance of real engineering materials critically depends on their resistance to small flaws under variable loading conditions (10–12), which, if not properly considered, may lead to unexpected fatigue failure and catastrophic accidents. In this regard, a comprehensive understanding of the role of DIMT in fatigue crack growth is still missing. This limits the application of DIMT in many key engineered systems requiring high fatigue reliability, such as trains, airplanes, spacecraft, and power plants.The complexity of this topic is reflected by the many mechanisms (13–15) that have been proposed so far on the possible influence of DIMT on fatigue crack growth. A recognized beneficial effect of DIMT is transformation-induced crack closure (TICC) (16). It is conventionally understood as a kind of crack closure similar to the classic plasticity-induced crack closure (17), in which the TRIP effect effectively contributes to the residual tensile deformation that is remaining in the crack wake. This gives rise to premature contact between the crack faces and results in a reduction in the effective crack driving force. Detailed theoretical and experimental studies (18–21) have revealed another main reason for this effect. It is the compressive residual stress generated by DIMT at the crack tip, which can locally compensate the far-field tensile stress. Another common explanation for crack retardation suggests that the occurrence of DIMT at the crack tip absorbs strain energy that would otherwise be available for crack growth. This effect is referred to as transformation-induced energy absorption (TIEA) (22, 23). It has also been shown that the DIMT can lead to crack path deflection, an effect referred to as transformation-induced crack deflection (TICD) (21, 24, 25). This mechanism leads to a zigzag crack path, which decelerates crack growth compared to a flat path (26). In addition, it can also increase the roughness level of crack surfaces, which in turn contributes to roughness-induced crack closure (RICC) (14, 27). In contrast to these effects that can reduce the crack growth rate, other studies (28, 29) have shown detrimental effects of DIMT. One of the main concerns is the brittleness of the fresh martensite that is formed as a transformation product at the crack tip (14, 21). This effect reduces the fracture toughness of the material (22), as brittle martensite is liable to crack initiation (18, 30). In this work, we investigate the effect of DIMT on fatigue crack growth in a model medium-Mn TRIP steel by conducting in situ fatigue tests in a scanning electron microscope (SEM). This allows capturing the detailed crack growth process and its interactions with the evolving microstructure. The study demonstrates both the beneficial and adverse effects of DIMT on fatigue crack growth. An unexpected finding is that these effects do not depend on the transformation process itself but on the characteristics of the transformation product, i.e., the hard and brittle martensite. They also show a strong dependence on the crack size and the mechanical stability of the host phase against transformation. These observations allow us to better understand and reconcile the sometimes contradictory fatigue phenomena that were reported for alloys with metastable phases. More specifically, we find that for different loading scenarios and alloy stabilities, different fatigue mechanisms can prevail during the different crack growth stages. These findings thus provide an in-depth understanding of the role of DIMT in fatigue crack growth. They also open up new pathways for designing fatigue-resistant alloys through optimal use of DIMT.     

新肾病1号方调控miR-199b-5p抑制肾小管上皮间充质转化改善肾纤维化的作用研究

目的 研究miR-199b-5p在新肾病1号方抗肾纤维化中的作用。方法 36只大鼠随机分为假手术组、模型组及新肾病1号方低、中、高剂量（9.69、19.38、38.76 g/kg）组和氯沙坦（50 mg/kg）组,每组6只。除假手术组外,其余各组采用左侧单侧输尿管梗阻方法建立大鼠肾纤维化模型,给予药物干预14 d后,检测各组大鼠肾功能;苏木素-伊红（HE）和Masson染色观察肾脏组织病理变化;对假手术组、模型组和新肾病1号方高剂量组大鼠肾脏组织进行miRNA测序,筛选差异表达miRNAs,qRT-PCR验证,并进行靶基因的基因本体（gene ontology,GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析,生物信息学分析miRNAs与上皮间质转化（epithelial-mesenchymal transition,EMT）、肾纤维化的关联性。免疫荧光法和Western blotting检测肾组织EMT相关蛋白表达情况。结果 与模型组比较,新肾病1号方组大鼠血清肌酐（serum creatin...     

基于少阴热化证浅析水热互结型狼疮肾炎

对于本文所述水热互结型狼疮肾炎,是以普遍认可的《金匮要略》中的"阳毒"为基础的一种分型,既往中医与本文所述相关疾病有很多,如"肾痹""赤丹"等,但少有人从六经辨证的角度去分析该病.现代中医对于狼疮肾炎有多种辨证方法.其中脏腑辨证多认为该病根源在肾,气血津液辨证多认为由热毒侵入血分所致,八纲辨证多认为该病以阴虚为主.而本...     

Cell transformation induces a cytoplasmic Ca2+ oscillator in Madin-Darby canine kidney cells

Alkaline stress transforms Madin-Darby canine kidney (MDCK) cells as indicated by loss of epithelial structure, multilayer cell growth and formation of foci. In the present study we report that transformed MDCK cells (MDCK-F cells) exhibit spontaneous and lasting oscillations of intracellular Ca²⁺ concentration ([Ca²⁺]_i), which are absent in non-transformed cells. Oscillations, as revealed by Fura-2 video imaging, were due to the activity of an inositol 1,4,5-trisphosphate-(InsP ₃)-sensitive Ca²⁺ store since their frequency was dependent on bradykinin concentration and they were abolished by the phosphoinositidase C inhibitor U73122. Moreover, blockers of the cytoplasmic Ca²⁺-ATPase, thapsigargin and 2,5-di-(tetr-butyl)-1,4-benzohydroquinone inhibited oscillatory activity. In contrast, neither injection of ruthenium red, ryanodine nor caffeine had any effect on oscillations. Analysis of the spatial distribution of [Ca²⁺]_i showed that Ca²⁺ transients originated from an initiation site constant for a given cell and spread through the cell as an advancing Ca²⁺ wave. Oscillations started in a random manner from single cells and spread over neighbouring cells, suggesting a kind of intercellular communication. We conclude that MDCK-F cells have acquired the ability for endogenous Ca²⁺ release through transformation. Oscillations are primarily due to the activity of an InsP ₃-sensitive cytosolic Ca²⁺ oscillator.