BACKGROUND & AIMS: :The skin as a barrier and immune organ is exposed to omnipresent environmental challenges such as irradiation or chemical and biologic hazards. Neuropeptides released from cutaneous nerves or skin and immune cells in response to noxious stimuli are mandatory for a fine-tuned regulation of cutaneous immune responses and tissue maintenance and repair. They initialize host immune responses, but are equally important for counter regulation of proinflammatory events. Interaction of the nervous and immune systems occurs both locally - at the level of neurogenic inflammation and immunocyte activation - and centrally - by controlling inflammatory pathways such as mononuclear activation or lymphocyte cytokine secretion. Consequently, a deregulated neurogenic immune control results in disease manifestation and frequently accompanies chronic development of cutaneous disorders. The current understanding, therapeutic options, and open questions of the role that neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide, neuropeptide Y, or others play in these events are discussed. Progress in this field will likely result in novel therapies for the management of diseases characterized by deregulated inflammation, tissue remodeling, angiogenesis, and neoplasm.

背景与目标： ：作为屏障和免疫器官的皮肤暴露于无处不在的环境挑战中，例如辐射或化学和生物危害。皮肤神经或皮肤释放的神经肽以及对有害刺激作出反应的免疫细胞对于皮肤免疫反应以及组织维持和修复的微调调节是必不可少的。它们可以启动宿主的免疫反应，但对于调节促炎事件也同样重要。通过控制诸如单核激活或淋巴细胞细胞因子分泌之类的炎症途径，神经和免疫系统的相互作用既在局部发生（在神经源性炎症和免疫细胞激活的水平），也发生在中央。因此，神经源性免疫控制失调导致疾病表现，并经常伴随皮肤疾病的慢性发展。讨论了有关P物质，降钙素基因相关肽，血管活性肠肽/垂体腺苷酸环化酶激活多肽，神经肽Y或其他在这些事件中发挥作用的神经肽的作用的当前理解，治疗选择和开放性问题。该领域的进展可能会导致新的疗法来治疗以炎症失调，组织重塑，血管生成和肿瘤为特征的疾病。

BACKGROUND & AIMS: :Over the past decade, the old idea that the bone marrow contains endothelial cell precursors has become an area of renewed interest. While some still believe that there are no endothelial precursors in the blood, even among those who do, there is no consensus as to what they are or what they do. In this review, we describe the problems in identifying endothelial cells and conclude that expression of endothelial nitric oxide synthase may be the most reliable antigenic indicator of the phenotype. The evidence for two different classes of endothelial precursors is also presented. We suggest that, though there is no single endothelial cell precursor, we may be able to use these phenotypic variations to our advantage in better understanding their biology. We also discuss how a variety of genetic, epigenetic, and methodological differences can account for the seemingly contradictory findings on the physiological relevance of bone marrow-derived precursors in normal vascular maintenance and in response to injury. Data on the impact of tumor type and location on the contribution of bone marrow-derived cells to the tumor vasculature are also presented. These data provide hope that we may ultimately be able to predict those tumors in which bone marrow-derived cells will have a significant contribution and design therapies accordingly. Finally, factors that regulate bone marrow cell recruitment to and function in the endothelium are beginning to be identified, and several of these, including stromal derived factor 1, monocyte chemoattractant factor-1, and vascular endothelial growth factor are discussed.

背景与目标： ：在过去的十年中，关于骨髓中含有内皮细胞前体的古老观念已经引起人们的广泛关注。尽管有些人仍然认为血液中没有内皮前体，即使在有血液的人中也没有，但是关于它们是什么或它们的行为尚无共识。在这篇综述中，我们描述了鉴定内皮细胞的问题，并得出结论，内皮一氧化氮合酶的表达可能是最可靠的表型抗原指示剂。还提供了两种不同类别的内皮前体的证据。我们建议，尽管没有单个内皮细胞前体，但我们也许能够利用这些表型变异来更好地了解它们的生物学特性。我们还将讨论各种遗传，表观遗传学和方法学上的差异如何解释在正常血管维持和对损伤的反应中骨髓来源的前体的生理相关性看似矛盾的发现。还提供了有关肿瘤类型和位置对骨髓来源的细胞对肿瘤脉管系统的影响的数据。这些数据提供了希望，使我们最终能够预测那些骨髓来源的细胞将发挥重要作用的肿瘤，并据此设计治疗方法。最后，已经开始确定调节骨髓细胞向内皮募集并在内皮中起作用的因子，并讨论了其中的几种，包括基质衍生因子1，单核细胞趋化因子-1和血管内皮生长因子。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs. We describe how a standard-enabled workflow can be used to produce types of design information, including multiple repositories and software tools exchanging information using a variety of data standards. Recently, the ACS Synthetic Biology journal has recommended the use of SBOL in their publications.

背景与目标： ：合成生物学工作流程由提供有关遗传零件信息的数据存储库，将这些零件组成电路的序列级设计工具，用于描绘这些设计的可视化工具，用于选择要创建系统的零件的遗传设计工具以及建模和仿真组成评估替代设计选择的工具。数据标准可以在这样的工作流程中随时交换信息，从而可以从各种来源连接存储库和工具。本文介绍了一种这样的工作流程，该流程除其他外，利用合成生物学开放语言（SBOL）来描述基因设计，使用系统生物学标记语言对这些设计进行建模，并利用SBOL Visual来可视化这些设计。我们描述了如何使用支持标准的工作流来产生类型的设计信息，包括多个存储库和使用各种数据标准交换信息的软件工具。最近，《 ACS合成生物学》杂志在其出版物中建议使用SBOL。

BACKGROUND & AIMS: :Over the past 50 years, annual killifishes arose as alternative model organisms for studies of vertebrate biology. The annual fish offers exceptional advantages for studies of genetics, genomics, developmental biology, population dynamics, ecology, biogeography, and evolution. They inhabit extremely variable freshwater environments in Africa and South America, have a short lifespan and a set of unique and fascinating developmental characteristics. Embryos survive within the dry substrate during the dry season, whereas the adult population dies. Thus, the survival of the populations is entirely dependent on the buried embryos that hatch the next rainy season. Although Old and New World species share similarities in their life cycle, they also have different adaptive responses associated with climate-related selective pressures. Therefore, contrasting different species from these areas is essential to understand unique adaptations to heterogeneous environment. A network of laboratories (United States, Czech Republic, Italy, Brazil, Chile, and Uruguay) is working and collaborating on many aspects of the biology of annual fishes. Participating researchers share projects and cross-training undergraduate and graduate students. These efforts resulted in two International Symposia (2010 and 2015) that took place in Montevideo and an international book. Herein, we summarize the progress made by this global community of scientists. Developmental Dynamics 246:807-811, 2017. © 2017 Wiley Periodicals, Inc.

背景与目标： ：在过去的50年中，一年生的鳞鱼成为了脊椎动物生物学研究的替代模式生物。一年生鱼类为遗传学，基因组学，发育生物学，种群动态，生态学，生物地理学和进化研究提供了特殊的优势。它们居住在非洲和南美极为不同的淡水环境中，寿命短，并具有一系列独特而引人入胜的发展特征。在干旱季节，胚胎在干燥的基质内存活，而成年种群死亡。因此，种群的生存完全取决于下一个雨季孵化的埋葬胚胎。尽管旧大陆和新大陆物种在生命周期上具有相似之处，但它们也具有与气候相关的选择压力相关的不同适应性反应。因此，对比这些地区的不同物种对于了解对异质环境的独特适应性至关重要。实验室网络（美国，捷克共和国，意大利，巴西，智利和乌拉圭）正在与一年生鱼类生物学的许多方面进行合作。参与研究的人员共享项目，并对本科生和研究生进行交叉培训。这些努力导致在蒙得维的亚举行了两次国际研讨会（2010年和2015年）和一本国际书籍。在此，我们总结了这个全球科学家社区所取得的进展。 Developmental Dynamics 246：807-811，2017.©2017 Wiley Periodicals，Inc.

BACKGROUND & AIMS: :We are developing biocompatible small-calibre vascular substitutes based on polymeric scaffolds that incorporate cell-matrix signals to enhance vascular cell attachment and function. Our graft scaffold comprises an outer electrostatically spun porous polyurethane layer seeded with smooth muscle cells, and a luminal polycaprolactone layer for endothelial cell attachment. Vascular cell adhesion properties of three vascular elastic fibre molecules, tropoelastin, fibrillin-1 and fibulin-5, have been defined, and adhesion fragments optimized. These fragments are being used to coat the scaffolds to enhance luminal endothelial cell attachment, and to regulate smooth muscle cell attachment and function. Tropoelastin-based cell seeding materials are also being developed. In this way, vascular cell-matrix biology is enhancing graft design.

背景与目标： ：我们正在开发基于高分子支架的生物相容性小口径血管替代品，该替代品结合了细胞基质信号以增强血管细胞的附着和功能。我们的移植支架包括一个外层静电纺丝的多孔聚氨酯层，其上植入了平滑肌细胞，以及一个内腔聚己内酯层，用于内皮细胞的附着。已经定义了三种血管弹性纤维分子（原弹性蛋白，原纤维蛋白-1和纤维蛋白-5）的血管细胞粘附特性，并优化了粘附片段。这些片段被用于包被支架以增强管腔内皮细胞的附着，并调节平滑肌细胞的附着和功能。基于弹性蛋白的细胞接种材料也在开发中。这样，血管细胞基质生物学正在增强移植物设计。

BACKGROUND & AIMS: :Arf and Rab proteins, members of small GTPases superfamily, localize to specific subcellular compartments and regulate intracellular trafficking. To carry out their cellular functions, Arfs/Rabs interact with numerous and structurally diverse effector proteins. Over the years, a number of Arf/Rab:effector complexes have been crystallized and their structures reveal shared binding modes including α-helical packing, β-β complementation, and heterotetrameric assemblies. We review available structural information and provide a framework for in-depth analysis of complexes. The unifying features that we identify are organized into a classification scheme for different modes of Arf/Rab:effector interactions, which includes "all-α-helical," "mixed α-helical," "β-β zipping," and "bivalent" modes of binding. Additionally, we highlight structural determinants that are the basis of effector specificity. We conclude by expanding on functional implications that are emerging from available structural information under our proposed classification scheme.

背景与目标： ：Arf和Rab蛋白是小GTPases超家族的成员，位于特定的亚细胞区室并调节细胞内运输。为了执行其细胞功能，Alfs / Rabs与众多结构上不同的效应蛋白相互作用。多年来，许多Arf / Rab：效应复合物已经结晶，其结构揭示了共享的结合模式，包括α-螺旋堆积，β-β互补和异四聚体组装。我们审查可用的结构信息，并提供用于复杂物深入分析的框架。我们确定的统一特征被组织为针对Arf / Rab：effector相互作用的不同模式的分类方案，其中包括“全α螺旋”，“混合α螺旋”，“β-β拉链”和“二价” ”的绑定方式。此外，我们重点介绍了结构决定子，这些决定子是效应子特异性的基础。最后，我们将对提议的分类方案下从可用结构信息中产生的功能含义进行扩展。

BACKGROUND & AIMS: :Integrin-linked kinase (ILK) has been implicated in the pathogenesis of proteinuria and congenital nephrotic syndrome. However, the function of ILK in glomerular podocyte in a physiologic setting remains unknown. In this study, a mouse model was generated in which ILK gene was selectively disrupted in podocytes by using the Cre-LoxP system. Podocyte-specific ablation of ILK resulted in heavy albuminuria, glomerulosclerosis, and kidney failure, which led to animal death beginning at 10 wk of age. Podocyte detachment and apoptosis were not observed at 4 wk of age, when albuminuria became prominent, indicating that they are not the initial cause of proteinuria. Electron microscopy revealed an early foot process effacement, as well as morphologic abnormality, in ILK-deficient podocytes. ILK deficiency caused an aberrant distribution of nephrin and alpha-actinin-4 in podocytes, whereas the localization of podocin and synaptopodin remained relatively intact. Co-immunoprecipitation demonstrated that ILK physically interacted with nephrin to form a ternary complex, and alpha-actinin-4 participated in ILK/nephrin complex formation. Therefore, ILK plays an essential role in specifying nephrin and alpha-actinin-4 distribution and in maintaining the slit diaphragm integrity and podocyte architecture. These results also illustrate that the integrin and slit diaphragm signals in podocytes are intrinsically coupled through an ILK-dependent mechanism.

背景与目标： 整联蛋白连接激酶（ILK）已被证明与蛋白尿和先天性肾病综合征的发病机制有关。然而，在生理环境中ILK在肾小球足细胞中的功能仍是未知的。在这项研究中，生成了小鼠模型，其中通过使用Cre-LoxP系统选择性地破坏了足细胞中的ILK基因。 ILK的足细胞特异性消融导致严重的蛋白尿，肾小球硬化和肾衰竭，从而导致动物从10周龄开始死亡。当蛋白尿变得突出时，在4周龄时未观察到足细胞脱离和凋亡，这表明它们不是蛋白尿的最初原因。电子显微镜检查显示，ILK缺陷足细胞有早期足突消失和形态异常。 ILK缺乏引起足细胞中nephrin和α-actinin-4的异常分布，而podocin和synaptopodin的定位仍然相对完整。免疫共沉淀表明ILK与nephrin物理相互作用形成三元复合物，而alpha-actinin-4参与了ILK / nephrin复合物的形成。因此，ILK在指定nephrin和α-actinin-4分布以及维持缝隙隔膜完整性和足细胞结构方面起着至关重要的作用。这些结果还表明，足细胞中的整联蛋白和裂膜信号是通过ILK依赖性机制固有地偶联的。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :The chemistry and biology of organic natural guanidines are reviewed, including the isolation, structure determination, synthesis, biosynthesis and biological activities of alkaloids, non-ribosomal peptides, guanidine-bearing terpenes, polyketides and shikimic acid derivatives from natural sources.

背景与目标： ：综述了有机天然胍的化学和生物学，包括天然来源生物碱，非核糖体肽，带有胍的萜烯，聚酮化合物和sh草酸衍生物的分离，结构测定，合成，生物合成和生物活性。

BACKGROUND & AIMS: :The present study focused on spermatophore structure, transfer, and subsequent destination inside bloodfeeding females of the species Triatoma infestans and Rhodnius neglectus. The morphology of the spermatophore differed between the species studied, such that in T. infestans, the shape was ovaloid, whereas in R. neglectus, the shape resembled a rod. Structures' spine-like cuticulars distributed across the inner surface of the vagina of both species were observed; however, the role of these cuticulars is unknown in Triatominae. In both species, there was an opening in the spermatophore exactly where the common oviduct is connected, thereby making it possible to confirm that the process of spermatozoid migration takes place through this opening. The results obtained show that the spermatophores of T. infestans and R. neglectus differ in size, shape, and structure. Therefore, they can be used as taxonomic markers and may provide information regarding physiology and evolution.

背景与目标： ：本研究的重点是三生无芒藻和疏叶红景天的雌性吸血雌性内的精子结构，转移和随后的目的。在所研究的物种之间，精子细胞的形态有所不同，因此在T. infestans中，形状为椭圆形，而在R. neglectus中，形状类似于杆状。观察到结构的脊柱状表皮分布在两个物种的阴道内表面上。然而，这些表皮的作用在Triatominae中是未知的。在这两个物种中，精子的确切开口都与普通输卵管相连，因此可以确认精子迁移过程是通过该开口进行的。获得的结果表明，T。infestans和R. neglectus的精原细胞在大小，形状和结构上都不同。因此，它们可以用作分类标记，并可以提供有关生理和进化的信息。

BACKGROUND & AIMS: :Hybrid breeding in wheat (Triticum aestivum L.) has the potential to deliver major yield increases. This is a requisite to guarantee food security for increasing population demands and to counterbalance the effects of extreme environmental conditions. Successful hybrid breeding in wheat relies on forced outcrossing while preventing self-pollination. To achieve this, research has been directed towards identifying and improving fertility control systems. To maximise cross-pollination and seed set, however, fertility control systems need to be complemented by breeding phenotypically distinct male and female lines. This review summarises existing and novel male sterility systems for wheat hybridisation. We also consider the genetic resources that can be used to alter wheat's floral development and spike morphology, with a focus on the genetic variation already available. Exploiting these resources can lead to enhanced outcrossing, a key requirement in the progress towards hybrid wheat breeding.

背景与目标： ：小麦（Triticum aestivum L.）的杂交育种有可能带来大幅增产。这是保证粮食安全以增加人口需求并平衡极端环境条件的影响的必要条件。小麦成功的杂交育种依赖于强制杂交，同时防止自花授粉。为了实现这一目标，研究一直致力于识别和改善生育控制系统。但是，为了使异花授粉和种子结实最大化，育种控制系统需要通过育成表型不同的雄性和雌性品系来补充。这篇综述总结了用于小麦杂交的现有和新颖的雄性不育系统。我们还考虑了可用于改变小麦花序发育和穗状形态的遗传资源，重点是现有的遗传变异。开发这些资源可以提高杂交效率，这是杂交小麦育种进展的关键要求。

BACKGROUND & AIMS: Background:Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders. Results:This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value < 0.05. The expression profiling and the functional enrichment analysis revealed the role of these genes in cell communication, signal transduction, and immune response. The protein-protein interaction showed the functional association of the source genes (CTNNB1, NNMT, PTCH1, CALD1, CXCL14, CXCL8, and TNFAIP3) with the target proteins, such as AXIN, MAPK, IL6, STAT, APC, GSK3B, and SHH. Conclusion:The integrated pathway analysis indicated the role of these genes in important physiological responses, such as cell cycle regulation, WNT, hedgehog, MAPK, and calcium signaling pathways during colorectal cancer. These pathways are involved in cell proliferation, chemotaxis, cellular growth, differentiation, tissue patterning, and cytokine production. The study shows the regulatory role of these genes in colorectal cancer and the pathways that can be effected after the dysregulation of these genes.

背景与目标： 背景：结直肠癌是世界范围内最常见的癌症，与疾病相关的死亡率很高。它是男女中第三大最常见的癌症，并且是全球因癌症而导致死亡的第二大原因。它是一种复杂且致命的疾病，由一组分子异质性疾病组成。
结果：本研究通过差异表达分析，系统生物学和蛋白质组学分析鉴定了CRC的潜在生物标志物。分析了十个公开可用的微阵列数据集，并从p值<0.05的差异表达基因列表中鉴定了七个潜在的生物标记。表达谱和功能富集分析揭示了这些基因在细胞通讯，信号转导和免疫应答中的作用。蛋白质相互作用显示源基因（CTNNB1，NNMT，PTCH1，CALD1，CXCL14，CXCL8和TNFAIP3）与目标蛋白质（例如AXIN，MAPK，IL6，STAT，APC，GSK3B和SHH）之间存在功能关联。
结论：综合通路分析表明这些基因在大肠癌的重要生理反应中的作用，例如细胞周期调控，WNT，刺猬，MAPK和钙信号通路。这些途径涉及细胞增殖，趋化性，细胞生长，分化，组织模式和细胞因子产生。研究表明这些基因在结直肠癌中的调节作用以及这些基因失调后可能发生的途径。

BACKGROUND & AIMS: PURPOSE OF REVIEW:Defective cell-mediated immunity is a major risk factor for cryptococcosis, a fatal disease if untreated. Cryptococcal meningitis (CM), the main presentation of disseminated disease, occurs through hematogenous spread to the brain from primary pulmonary foci, facilitated by yeast virulence factors. We revisit remarkable recent improvements in the prevention, diagnosis and management of CM. RECENT FINDINGS:Cryptococcal antigen (CrAg), main capsular polysaccharide of Cryptococcus spp. is detectable in blood and cerebrospinal fluid of infected patients with point of care lateral flow assays. Recent World Health Organization guidelines recommend 7-day amphotericin B plus flucytosine, then 7-day high dose (1200 mg/day) fluconazole for induction treatment of HIV-associated CM. Management of raised intracranial pressure, a consequence of CM, should rely mainly on daily therapeutic lumbar punctures until normalisation. In HIV-associated CM, following introduction of antifungal therapy, (re)initiation of antiretroviral therapy should be delayed by 4-6 weeks to prevent immune reconstitution inflammatory syndrome, common in CM. CM is a fatal disease whose diagnosis has recently been simplified. Treatment should always include antifungal combination therapy and management of raised intracranial pressure. Screening for immune deficiency should be mandatory in all patients with cryptococcosis.

背景与目标： 审查目的：细胞介导的免疫缺陷是隐球菌病的主要危险因素，隐球菌病是未经治疗的致命疾病。隐球菌性脑膜炎（CM）是弥漫性疾病的主要表现形式，通过血源性扩散从原发性肺病灶扩散到大脑，并受到酵母毒力因子的促进。我们回顾了最近在CM的预防，诊断和管理方面的显着改善。
最新发现：隐球菌抗原（CrAg），隐球菌的主要荚膜多糖。通过即时护理侧向流动检测，可以在感染患者的血液和脑脊液中检测到。世界卫生组织最近的指南建议使用7天的两性霉素B加氟胞嘧啶，然后7天的大剂量（1200毫克/天）氟康唑来诱导治疗与HIV相关的CM。 CM引起的颅内压升高的管理应主要依靠每日治疗性腰椎穿刺直至恢复正常。在与HIV相关的CM中，在引入抗真菌治疗后，应将（重新）开始抗逆转录病毒治疗推迟4-6周，以防止CM中常见的免疫重建炎症综合症。 CM是一种致命疾病，最近已简化了诊断。治疗应始终包括抗真菌药物联合治疗和颅内压升高的治疗。在所有隐球菌病患者中，必须对免疫缺陷进行筛查。

BACKGROUND & AIMS: :There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liver disease (NAFLD). In particular, there is a need for diagnostic and prognostic tools, as well as predictive biomarkers that reflect the efficacy of interventions, as described by the BEST criteria (Biomarkers, EndpointS, and other Tools Resource). This review covers the various liver collagens, their functional role in tissue homeostasis and delineates the common nomenclature for biomarkers based on BEST criteria. It addresses the common confounders affecting serological biomarkers, and describes defined collagen epitope biomarkers that originate from the dynamic processes of extracellular matrix (ECM) remodelling during liver injury.

背景与目标： ：对能够安全，可重复地预测纤维化阶段和慢性肝病（CLD）结局的高质量液体生物标志物的需求未得到满足。由于诸如非酒精性脂肪肝疾病（NAFLD）之类的疾病在全球的普遍流行，因此对此类标记物的需求日益增加。特别是，需要一种诊断和预后工具，以及反映干预效果的预测性生物标志物，如BEST标准（生物标志物，EndpointS和其他工具资源）所述。这篇综述涵盖了各种肝脏胶原蛋白，它们在组织体内稳态中的功能作用，并根据BEST标准描述了生物标志物的常用命名法。它解决了影响血清生物标志物的常见混杂因素，并描述了确定的胶原蛋白表位生物标志物，其起源于肝损伤期间细胞外基质（ECM）重塑的动态过程。