Molecular Mechanisms Underlying Motor Axon Guidance in Drosophila

Decoding the molecular mechanisms underlying axon guidance is key to precise understanding of how complex neural circuits form during neural development. Although substantial progress has been made over the last three decades in identifying numerous axon guidance molecules and their functional roles, little is known about how these guidance molecules collaborate to steer growth cones to their correct targets. Recent studies in Drosophila point to the importance of the combinatorial action of guidance molecules, and further show that selective fasciculation and defasciculation at specific choice points serve as a fundamental strategy for motor axon guidance. Here, I discuss how attractive and repulsive guidance cues cooperate to ensure the recognition of specific choice points that are inextricably linked to selective fasciculation and defasciculation, and correct pathfinding decision-making.     

Dominant Effects of the Diet on the Microbiome and the Local and Systemic Immune Response in Mice

Outside the nutrition community the effects of diet on immune-mediated diseases and experimental outcomes have not been appreciated. Investigators that study immune-mediated diseases and/or the microbiome have overlooked the potential of diet to impact disease phenotype. We aimed to determine the effects of diet on the bacterial microbiota and immune-mediated diseases. Three different laboratory diets were fed to wild-type mice for 2 weeks and resulted in three distinct susceptibilities to dextran sodium sulfate (DSS)-induced colitis. Examination of the fecal microbiota demonstrated a diet-mediated effect on the bacteria found there. Broad-spectrum antibiotics disturbed the gut microbiome and partially eliminated the diet-mediated changes in DSS susceptibility. Dietary changes 2 days after DSS treatment were protective and suggested that the diet-mediated effect occurred quickly. There were no diet-mediated effects on DSS susceptibility in germ-free mice. In addition, the diet-mediated effects were evident in a gastrointestinal infection model (Citrobacter rodentium) and in experimental autoimmune encephalomyelitis. Taken together, our study demonstrates a dominant effect of diet on immune-mediated diseases that act rapidly by changing the microbiota. These findings highlight the potential of using dietary manipulation to control the microbiome and prevent/treat immune-mediated disease.     

Mechanisms Underlying Robustness and Tunability in a Plant Immune Signaling Network

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二甲双胍抗肿瘤作用及其分子机制的研究进展

二甲双胍是全球范围内治疗2型糖尿病最常用的药物之一,具有使用方便、疗效好、价格低廉且毒副作用小等优点。近年来大量的流行病学研究及体内外实验研究发现二甲双胍能够用于多种肿瘤的治疗及预防,然而其分子机制尚不十分明确;主要包括调节体内胰岛素/IGF-1轴、激活AMPK信号通路、调控micro RNAs的表达、活化Caspase分子、阻断AGEs-RAGE系统等,这些机制为将来二甲双胍应用于肿瘤的预防及临床治疗提供了重要的理论依据。本文针对糖尿病治疗药物二甲双胍在抗肿瘤中的作用及其分子机制进行全面综述。     

Mechanisms Underlying the Anti-Tumoral Effects of Citrus bergamia Juice

Based on the growing deal of data concerning the biological activity of flavonoid-rich natural products, the aim of the present study was to explore in vitro the potential anti-tumoral activity of Citrus Bergamia (bergamot) juice (BJ), determining its molecular interaction with cancer cells. Here we show that BJ reduced growth rate of different cancer cell lines, with the maximal growth inhibition observed in neuroblastoma cells (SH-SY5Y) after 72 hs of exposure to 5% BJ. The SH-SY5Y antiproliferative effect elicited by BJ was not due to a cytotoxic action and it did not induce apoptosis. Instead, BJ stimulated the arrest in the G1 phase of cell cycle and determined a modification in cellular morphology, causing a marked increase of detached cells. The inhibition of adhesive capacity on different physiologic substrates and on endothelial cells monolayer were correlated with an impairment of actin filaments, a reduction in the expression of the active form of focal adhesion kinase (FAK) that in turn caused inhibition of cell migration. In parallel, BJ seemed to hinder the association between the neural cell adhesion molecule (NCAM) and FAK. Our data suggest a mechanisms through which BJ can inhibit important molecular pathways related to cancer-associated aggressive phenotype and offer new suggestions for further studies on the role of BJ in cancer treatment.     

Winemaking and Bioprocesses Strongly Shaped the Genetic Diversity of the Ubiquitous Yeast Torulaspora delbrueckii

The yeast Torulaspora delbrueckii is associated with several human activities including oenology, bakery, distillery, dairy industry, etc. In addition to its biotechnological applications, T. delbrueckii is frequently isolated in natural environments (plant, soil, insect). T. delbrueckii is thus a remarkable ubiquitous yeast species with both wild and anthropic habitats, and appears to be a perfect yeast model to search for evidence of human domestication. For that purpose, we developed eight microsatellite markers that were used for the genotyping of 110 strains from various substrates and geographical origins. Microsatellite analysis showed four genetic clusters: two groups contained most nature strains from Old World and Americas respectively, and two clusters were associated with winemaking and other bioprocesses. Analysis of molecular variance (AMOVA) confirmed that human activities significantly shaped the genetic variability of T. delbrueckii species. Natural isolates are differentiated on the basis of geographical localisation, as expected for wild population. The domestication of T. delbrueckii probably dates back to the Roman Empire for winemaking (∼1900 years ago), and to the Neolithic era for bioprocesses (∼4000 years ago). Microsatellite analysis also provided valuable data regarding the life-cycle of the species, suggesting a mostly diploid homothallic life. In addition to population genetics and ecological studies, the microsatellite tool will be particularly useful for further biotechnological development of T. delbrueckii strains for winemaking and other bioprocesses.     

腺苷及其衍生物的心血管效应和作用机制

在实验中观察了腺苷及其衍生物的心血管效应和作用机制,结果表明：（１）腺苷和２－氯腺苷先引起由颈动脉体化学感受器内的Ａ２受体所中介的血压短暂升高,随之为心血管系统Ａ１和Ａ２受体中介的持久而明显的血压降低;（２）腺苷受体激动剂环戊腺苷抑制窦房结起搏细胞的电生理活动;（３）环戊腺苷减弱异丙肾上腺素诱发的早发和迟发性后除极及触发电活动;（４）内源性腺苷参与无氧所致的心率减慢;（５）预缺血时腺苷受体的激活及     

量子点细胞毒性及其作用机制

纳米粒子(NPS)在工业和研究中的使用急剧增加,因而这种材料面临一个其潜在毒性的问题。不幸的是,对纳米颗粒与纳米/生物界面可能发生的相互作用没有足够的了解。广大科技工作者正在积极寻求日益关注的纳米技术对人类的影响答案。我们将从NPS在生物媒体中的浓度,尺寸大小,电荷,和配位体的稳定性方面来了解纳米粒子的性质和他们在生物环境中对细胞毒所起的作用;并初步探讨已知的机制,量子点可以破坏细胞,包括氧化应激引起的活性氧(ROS)。微小浓度量子点足以造成长期持久的,甚至是跨代的影响。本文讨论了从纳摩尔到皮摩尔浓度的诱导细胞损伤的量子点(QDS)的浓度,这意味着含镉量子点可以发挥表观遗传毒性,纳米基因毒性,重金属基因的毒性。在此为评估包括量子点的在内的纳米毒性的的纳米材料,我们采用量子点作为一个例证,来阐述以科学为基础的发展到纳米毒理学的相关的问题。     

Molecular Mechanisms Underlying the Anti-depressant Effects of Resveratrol: a Review

Major depression is a public health problem, affecting 121 million people worldwide. Patients suffering from depression present high rates of morbidity, causing profound economic and social impacts. Furthermore, patients with depression present cognitive impairments, which could influence on treatment adherence and long-term outcomes. The pathophysiology of major depression is not completely understood yet but involves reduced levels of monoamine neurotransmitters, bioenergetics, and redox disturbances, as well as inflammation and neuronal loss. Treatment with anti-depressants provides a complete remission of symptoms in approximately 50% of patients with major depression. However, these drugs may cause side effects, as sedation and weight gain. In this context, there is increasing interest in studies focusing on the anti-depressant effects of natural compounds found in the diet. Resveratrol is a polyphenolic phytoalexin (3,4′,5-trihydroxystilbene; C₁₄H₁₂O₃; MW 228.247 g/mol) and has been found in peanuts, berries, grapes, and wine and induces anti-oxidant, anti-inflammatory, and anti-apoptotic effects in several mammalian cell types. Resveratrol also elicits anti-depressant effects, as observed in experimental models using animals. Therefore, resveratrol may be viewed as a potential anti-depressant agent, as well as may serve as a model of molecule to be modified aiming to ameliorate depressive symptoms in humans. In the present review, we describe and discuss the anti-depressant effects of resveratrol focusing on the mechanism of action of this phytoalexin in different experimental models.     

The Mechanisms Underlying the Formation of Systemic Hemodynamic Reactions: Role of Initial Vessel Tone and Arterial Pressure

A review of the experimental materials describing the relationships between the initial (background) vascular tone and arterial pressure, on the one hand, and reactivity of the arterial system, on the other. Experiments were carried out on anesthetized rats under arterial hypotension caused by orthostasis or vasoactive agents, such as papaverine and sodium nitroprusside, and arterial hypertension resulting from volume expansion. It has been proposed that these relationships are based on changes in the amplitude of transmural pressure in arterial vessels.     

High Concentration of Vitamin E Decreases Thermosensation and Thermotaxis Learning and the Underlying Mechanisms in the Nematode Caenorhabditis elegans

α-tocopherol is a powerful liposoluble antioxidant and the most abundant isoform of vitamin E in the body. Under normal physiological conditions, adverse effects of relatively high concentration of vitamin E on organisms and the underlying mechanisms are still largely unclear. In the present study, we used the nematode Caenorhabditis elegans as an in vivo assay system to investigate the possible adverse effects of high concentration of vitamin E on thermosensation and thermotaxis learning and the underlying mechanisms. Our data show that treatment with 100–200 µg/mL of vitamin E did not noticeably influence both thermosensation and thermotaxis learning; however, treatment with 400 µg/mL of vitamin E altered both thermosensation and thermotaxis learning. The observed decrease in thermotaxis learning in 400 µg/mL of vitamin E treated nematodes might be partially due to the moderate but significant deficits in thermosensation, but not due to deficits in locomotion behavior or perception to food and starvation. Treatment with 400 µg/mL of vitamin E did not noticeably influence the morphology of GABAergic neurons, but significantly decreased fluorescent intensities of the cell bodies in AFD sensory neurons and AIY interneurons, required for thermosensation and thermotaxis learning control. Treatment with 400 µg/mL of vitamin E affected presynaptic function of neurons, but had no remarkable effects on postsynaptic function. Moreover, promotion of synaptic transmission by activating PKC-1 effectively retrieved deficits in both thermosensation and thermotaxis learning induced by 400 µg/mL of vitamin E. Therefore, relatively high concentrations of vitamin E administration may cause adverse effects on thermosensation and thermotaxis learning by inducing damage on the development of specific neurons and presynaptic function under normal physiological conditions in C. elegans.     

编者按：中药的抗炎作用及分子机制

Anti-inflammatory effects and underlying molecular mechanisms of traditional Chinese medicine     

Mechanisms Underlying the Opposing Effects of P2Y Receptors on the Cell Cycle

The purinergic P2Y receptors are critical determinants of physiological function playing diverse roles in cell proliferation, differentiation, and survival. However, in cancer cells they have been reported to assume contradictory roles at times, thus causing inhibition of proliferation, cell death, and apoptosis. A critical evaluation and analysis of the existing experimental data show that this response is caused by multiple mechanisms at the level of the ligand, receptor, G protein, intracellular signaling, such as the mitogen activated protein kinase pathways and surface expression. This review addresses the impact of these factors in determining the outcome of P2Y receptor activation. Working in conjunction, these factors can act to produce the observed opposing effects on the cell cycle. Thus, they are important factors in the pathogenesis and control of cancer.     

Opening the Black Box of Developmental Experiments: Behavioural Mechanisms Underlying Long‐Term Effects of Early Social Experience

Typically, animals spend a considerable portion of their time with social interactions involving mates, offspring, competitors and group members. The social performance during these interactions can strongly depend on the social environment individuals have experienced early in life. Despite a considerable number of experiments investigating long‐term effects of the early social environment, our understanding of the behavioural mechanisms mediating these effects is still limited, mainly for two reasons. (1) Only in few experimental studies have researchers actually observed and quantified the behaviour of their study animals during the social treatment. (2) Even if differences in social interactions between social rearing treatments are reported, these differences might not be causally linked to any observed long‐term effects later in life. The aim of this review was to investigate whether behavioural records of animals during the experimental manipulation of their social environment can help (1) identifying behavioural mechanisms involved in a long‐term effect and (2) obtaining a better understanding of the long‐term consequences of early manipulations. First, I review studies that manipulated the social environment at an early stage of the ontogeny, observed the social interactions and behaviour during the social experience phase and subsequently tested the performance in social and non‐social behavioural tasks at a later life stage. In all reviewed studies, treatment differences were reported both in social interactions during the social experience phase and in social and/or non‐social behaviours later in life. Second, I discuss four classes of behavioural mechanisms that can cause the reported long‐term effects of social experience, namely learning by experience, social learning, sensory stimulation and social cueing. I conclude that social interactions during the social experience phase should always be recorded for at least two reasons. Knowledge about how the social interactions differ between rearing treatments (1) permits researchers to formulate hypotheses about candidate mechanisms causing long‐term effects on behaviour and (2) can help to interpret unexpected outcomes of developmental experiments. Finally, I propose that as a crucial ultimate step towards understanding effects of the early social environment, we should develop targeted experiments testing for the causality of identified candidate mechanism.     

Local and Systemic Effects of Brassinosteroid Perception in Developing Phloem

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