如何将小胶质细胞向有益功能重编程

小胶质细胞是一种非神经起源的脑细胞,它可以协调对各种损伤的炎症反应,包括围产期脑中的缺氧/缺血或母体/胎儿感染。实验研究已经证明小胶质细胞能够识别病原体或受损细胞,从而激活细胞毒性反应,从而加剧脑损伤。然而,小胶质细胞在对损伤的反应中显示出巨大的可塑性,并且还可以促进炎症和组织再生的消退。尽管小胶质细胞在脑病理学中起着关键作用,对于控制小胶质细胞不同表型的细胞机制的研究却才刚刚崭露头角。这篇文章回顾了推动小胶质细胞向有益功能发展的新兴策略,总结了涉及表型转换潜在的分子机制的研究。这些方法包括使用药理学试剂,细胞因子,脂质信使或微小RNA,以及免疫调节细胞的营养方法或疗法来处理小胶质细胞。对小胶质细胞向促再生功能重编程相关的分子机制的分析指出,能量代谢在塑造小胶质细胞功能中起到核心作用。因此,可以通过调控代谢途径,来预防炎性小胶质细胞的有害作用并控制脑病症中的过度炎症反应。

Retinoid receptor-related orphan receptor alpha： a key gene setting brain circuits

The retinoid receptor-related orphan receptor alpha（RORα） is thought to act as a constitutive activator of transcription by binding to the ROR response element（RORE） of target genes. Several mouse models in which RORα is defective have revealed the decisive roles of RORα on the development, maturation and neuroprotection of various cerebral regions including the cerebellar and somatosensory systems. We have recently shown that RORα is needed for accurate thalamic sensory system organization and somatosensory cortex development. The phenotype of various RORα deficient mice models（staggerer mutant or mouse lacking RORα in specific somatosensory regions） is, in part, reminiscent of what has been described in mice lacking thyroid hormone triiodothyronine（T3）. As in in vitro studies or in other models, our studies strongly suggest that the T3/RORα-pathway, among others, is in part responsible for the staggerer phenotype. We have indeed identified some genes that were both regulated by T3 and RORα and that are known to be implicated in the cerebellar or somatosensory system development. Moreover, several groups have shown that RORα is at the crossroad of many biological processes and pathologies, including psychiatric and degenerative disorders. In particular, defective RORα-signalling has been demonstrated in humans to be associated with the emergence of autistic-like disorders. We believe that determining the appropriate amount of RORα activity could be crucial in detecting and preventing the emergence of specific brain diseases.

Sorafenib Acts through VEGFR-2 Inhibition in a Metastatic Clear-Cell Sarcoma of the Kidney

We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.

Diet Composition of the Salamander Lyciasalamandra luschani basoglui on the Greek Island of Kastellorizo in the Southeast Aegean Sea

The diet composition of the Lycian salamander Lyciasalamandra luschani basoglui across both age and sex groups was studied. Specimens were collected from a small island in the Southeast Aegean Sea. The dominant prey group of juveniles consisted of Collembola, while Coleoptera dominated the diet of males and females. The number and size of prey items consumed by males and females of L. luschani basoglui were quite similar, while juveniles ate fewer items of much smaller size. The numerical abundance along with the four measures of the size of prey permitted discrimination among males, females and juveniles. Although discrimination between adults and juveniles is expected due to dissimilarity in body size, discrimination between males and females remains inexplicable despite their similarity in body size. Future studies should be focused on understanding how and why prey choice differs between sexes in L. luschani basoglui.

Nerves and hydrogen peroxide： how old enemies become new friends

ROS and nerves play together during the regeneration process： For many years, the role of reactive oxygen species （ROS） in neurobiology has mainly focused on its pathological implications in neurodegenerative diseases. Contrasting with this view, ROS were recently put forward as key positive signals for axon growth and repair, highlighting beneficial functions of ROS signalling in the vertebrate adult brain （Borquez et al., 2016）.

Combined effect of <i>CYP2C9</i>and <i>VKORC1</i>polymorphisms on warfarin maintenance dose in Omani patients

Excepting host genetic factors, other influences on the pharmacokinetic and pharmacodynamic behavior of warfarin are subject to variations during the treatment despite attempts to stabilize the INR. In 214 Omani patients on warfarin therapy, we evaluated the extent of influence of known genetic predictors of warfarin dose variability, namely CYP2C9, CYP4F2 and VKORC1 gene polymorphisms in a genetically heterogeneous patient population. When patients were stratified according to their daily warfarin maintenance dose (to maintain INR between 2 and 3) into “low dose” (sensitive), “medium dose” (intermediate) and “high dose” (resistance) groups, overall, seven patients with three or four mutant alleles fell in the sensitive group and consequently 25% (7 out of 28) of at risk patients for over anticoagulation can be recognized by prospective pharmacogenetic testing in this patient population. Pre-prescription genotyping of these loci prior to therapy initiation will therefore benefit a small fraction of this population.

Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by resequencing.RESULTS:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD marker.Using the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in MORC4.The association between the CLDN2 marker and CD was not replicated in the familybased study.Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

Effect of SOD1 Overexpression on the 20S Proteasome during Aging

Metabolism of oxygen derivatives has been shown to be altered in Down syndrome (DS) due to the overexpression of the Cu/Zn superoxide dismutase gene ( SOD-1) on chromosome 21. Transgenic mice for the human SOD1 gene (h SOD1) exhibit some features of the syndrome. Oxidation of proteins and oxidative stress are involved in normal and pathological aging. The proteasome is an adaptative system to eliminate the modified proteins which can be deleterious. As SOD1 overexpression has been shown to be either deleterious or protective according to tissues and paradigms, we have measured in function of age the 20S proteasome activities in neural tissues (cerebral hemisphere, cerebellum and cortex) and in the thymus and the heart from control and transgenic mice. Indeed, although SOD1 overexpression is very deleterious in thymus and heart, it has little effect in cerebral hemisphere and cortex depending on the proteolytic activity measured. Conversely in the cerebellum the three proteolytic activities decrease dramatically in transgenic old mice while it was not modified in control mice during aging. The results of this study suggest that some phenotypes of DS present in thymus, heart and neural tissues of h SOD1 transgenic mice might be partially due to the modulation of the 20S proteasome expression during aging.

HLA and lung transplantation

Lung transplantation is increasingly practiced for patients with end-stage lung disease.The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies,mainly directed against the protein products of the HLA complex of the organ donor.While the association between antibody mediated rejection and ailograft damage has been well established in renal and heart transplantation,it has not yet been well characterized in lung transplantation.This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class Ⅰ and Ⅱ antigens.The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or de novo posttransplant circulating antibodies.Finally,potential mechanisms,which may act individually or in combination,of antibody mediated damage to solid organ transplants are considered.

法国网络文学研究

法国本土网络文学刚刚起步,其现状如何?本文将首先概述网络对法国当代文学生产的影响,然后介绍一些特定网站(法国网络小说的创作平台与中国网络小说的法译网站)的形成及运作,最终从理论层面展望未来的法国网络文学研究。

A Formal Passage From a System of Boltzmann Equations for Mixtures Towards a Vlasov-Euler System of Compressible Fluids

A formal asymptotics leading from a system of Boltzmann equations for mixtures towards either Vlasov-Navier-Stokes or Vlasov-Stokes equations of incompressible fluids was established by the same authors and Etienne Bernard in: A Derivation of the Vlasov-Navier-Stokes Model for Aerosol Flows from Kinetic Theory Commun. Math. Sci., 15: 1703–1741(2017) and A Derivation of the Vlasov-Stokes System for Aerosol Flows from the Kinetic Theory of Binary Gas Mixtures. KRM, 11: 43–69(2018). With the same starting point but with a different scaling, we establish here a formal asymptotics leading to the Vlasov-Euler system of compressible fluids. Explicit formulas for the coupling terms are obtained in two typical situations: for elastic hard spheres on one hand, and for collisions corresponding to the inelastic interaction with a macroscopic dust speck on the other hand.

Theranostics:纳米热疗法或可软化肿瘤,提高癌症靶向疗法的治疗效率

肿瘤的机械阻力和标准疗法的附带损伤往往会阻碍抵御癌症的效果，近日，来自法国国家健康与医学研究所等机构的研究人员通过对肿瘤加热成功软化了恶性肿瘤，这种方法称之为纳米热疗法，其能够让肿瘤对治疗制剂更加敏感，相关研究刊登于国际杂志Theranostics上。

Design,synthesis and bioactivity of chalcones and its analogues

The Vernohia anthelmintica L.＇s extract is one of the most popular Uygur medicines used for vitiligo. It is believed that the chalcone compounds of the plant play an important role in the treatment since they may activate tyrosinase and improve melanin production. In this study, twenty-one chalcones and nine analogues were synthesized in view of three different components of chalcone（A, B ring and a,b-unsaturated carbonyl）. After biological evaluation of their activity on tyrosinase in cell-free systems,the result showed that most compounds（except polyhydroxy chalcones） possess activator effect on the tyrosinase, especially for 13a–15a, 20 a and 1b, which bearing a comparable activity to the positive control8-MOP. SAR of these tyrosinase activator was summed up for the first time as well. Finally, compound 13 a was found to increase melanin contents and tyrosinase activity 1.75 and 1.3 fold, respectively, compared with that of untreated murine B16 cells at the concentration of 40 mg/m L.