伤寒-鼠伤寒重组株Vi4072在小鼠中定居及血清学效果观察试验

将编码Vi抗原的基因克隆到减毒的鼠伤寒沙门氏菌中组建的基因重组株Vi4072,以3×10~8CFU一次口服感染Balb/C小鼠,4天后按7,14,21,28,35,42,49,56,63,70天的间隔收集分离小鼠的集合淋巴结,肝,脾.鉴别是否有本菌出现,并检测血清和小肠匀浆液中的vi抗体.结果表明,感染后49天仍可从脾中分离到该菌;70天仍可从血清和小肠匀浆液中测出vi抗体。     

Effect of dimethylglycine and trimethylglycine (Betaine) on the response of Atlantic salmon (Salmo salar L.) smolts to experimental Vibrio anguillarum infection

Atlantic salmon (Salmo salar L.) were fed on a control diet or experimental diets containing betaine (15 mg g^-1) or dimethylglycine (DMG, I mg g^-1 or 5 mg g^-1). After 10 weeks of feeding, resistance to infection was assessed following inoculation with Vibrio anguillarum. Total blood and differential leucocyte counts were made, and plasma lysozyme and ceruloplasmin were assayed as non-specific humoral factors. The mortality during the bacterial exposure was of the same magnitude in all feeding groups. Betaine or DMG had no effect on the 'basal' levels of plasma total protein, lysozyme or ceruloplasmin, but 3 days postinjection the lysozyme and ceruloplasmin levels were higher in the control group compared with the experimental groups. In both DMG groups, the lymphocyte response took place 1-2 weeks earlier than in the control or betaine supplemented group indicating that DMG has an immunomodulating effect on salmon.     

ABR frequency tuning curves in dolphins

Tone-tone masking was used to determine auditory brain-stem response tuning curves in dolphins (Tursiops truncatus) in a simultaneous-masking paradigm. The Q ₁₀ of the curves was as large as 16–19 in the frequency range 64–128 kHz. In the range 45–16 kHz, Q ₁₀ decreased proportionally to the frequency with the bandwidth of the curves being constant, about 3.5–4 kHz at the 10-dB level. Tuning curves below 45 kHz are supposed to reflect broad spectral bandwidth of the probe's effective part which is no longer than 0.5 ms, irrespective of actual probe duration. Tuning curves above 64 kHz are supposed to reflect the real frequency tuning of the dolphin's auditory system.Abbreviations ABR auditory brain stem response - AP action potential     

Antitumor response to recombinant murine interferon γ correlates with enhanced immune function of organ-associated,but not recirculating cytolytic T lymphocytes and macrophages

The mechanism of therapeutic activity for recombinant murine interferon-(rMu IFN) in the treatment of metastatic disease was investigated by comparing effector cell augmentation with therapeutic activity in mice bearing experimental lung metastases (B16-BL6 melanoma). Effector cell functions in spleen, peripheral blood, and lung (the tumor-bearing organ) were tested after 1 week and 3 weeks of rMu IFN administration (i.v. three times per week). Natural killer (NK), lymphokine-activated killer (LAK), cytolytic T lymphocyte (CTL) activities against specific and nonspecific targets, and macrophage tumoristatic activity were measured. rMu IFN demonstrated immunomodulatory activity in most assays of immune function. The optimal therapeutic protocol of rMu IFN (2.5×10⁶ U/kg, three times per week) prolonged survival and decreased the number of pulmonary metastatic foci. This therapeutic activity was correlated with specific CTL activity from pulmonary parenchymal mononuclear cells (PPMC), but not from spleen or blood. Macrophage tumoristatic activity in PPMC also correlated with therapeutic activity, but activity in alveolar macrophages did not. However, therapeutic activity did not correlate with NK or LAK activity at any site. These results demonstrate that the optimal therapeutic protocol is the same as the optimal immunomodulatory dose for pulmonary CTL and macrophage activities. Furthermore, while immunological monitoring may help to optimize treatment protocols, current monitoring procedures that use readily accessible sites, particularly peripheral blood, may not accurately predict the therapeutic efficacy of biological response modifiers in clinical trials.By acceptance of this article, the publisher or recipient acknowledges the right of the US. Government to retain a nonexclusive, royalty-free license in and to any copyright covering the articleThis research was sponsored by the DHHS, under contract N01-23910 with Program Resources Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government     

Phase shifts of the adult locomotor activity rhythm in Calliphora vicina induced by non-steroidal ecdysteroid agonist RH 5849

RH 5849, a non-steroidal ecdysteroid mimic, was found to cause consistent phase shifts in the circadian rhythm of locomotor activity of the blowfly, Calliphora vicina. This compound causes phase advances in the early subjective night and phase delays in the late subjective night. This effect is the opposite, but not the mirror image of the phase response curve obtained for 1 h light pulses. This suggests that ecdysteroids might act as entraining agents via the output pathway by feedback to clock neurons in the brain. A computer model based on 12 pacemaker neurons with circadian periods ( values) from short to long without simulated feedback from the ecdysteroid system becomes arrhythmic; with feedback, the oscillators become synchronized to a common period. The possible role of ecdysteroids as endogenous synchronizing agents in the insect circadian system is discussed.     

中华蜜蜂和意大利蜜蜂感染囊状幼虫病毒后免疫及发育相关基因表达比较

【目的】本文旨在探究囊状幼虫病毒(sacbrood virus, SBV)对中华蜜蜂(Apis cerana cerana,简称中蜂)和意大利蜜蜂(Apis mellifera ligustica,简称意蜂)工蜂幼虫发育和免疫基因、营养代谢基因、抗病毒基因、细胞发育及代谢相关基因表达的影响。【方法】从蜂群中移取2日龄的中蜂和意蜂幼虫,在培养箱(34℃, RH 85%)进行人工饲养,3日龄时接种SBV病毒,每天观察记录死亡情况,并通过实时定量PCR (real-time quantitative polymerase chain reaction, RT-qPCR)检测4日龄和7日龄幼虫体内SBV基因相对表达量,及免疫基因(Apidaecin、Abaecin、Hymenoptaecin、Denfensin、Lys-1、Pgrp-lc、Kenny、Domeless)、营养代谢基因(Ilp1、Hex110、Vg)、抗病毒基因(Dis3、Dicer、Ago1)、细胞组成及发育调控基因(Vhdl、Co-1-iv)以及细胞代谢和调控基因(Mta1)的表达水平。【结果】通过分析比较发现,感染相同剂量...     

Age-mediated gut microbiota dysbiosis promotes the loss of dendritic cells tolerance

The old age-related loss of immune tolerance inflicts a person with a wide range of autoimmune and inflammatory diseases. Dendritic cells (DCs) are the sentinels of the immune system that maintain immune tolerance through cytokines and regulatory T-cells generation. Aging disturbs the microbial composition of the gut, causing immune system dysregulation. However, the vis-à-vis role of gut dysbiosis on DCs tolerance remains highly elusive. Consequently, we studied the influence of aging on gut dysbiosis and its impact on the loss of DC tolerance. We show that DCs generated from either the aged (DC^Old) or gut-dysbiotic young (DC^Dysbiotic) but not young (DC^Young) mice exhibited loss of tolerance, as evidenced by their failure to optimally induce the generation of Tregs and control the overactivation of CD4⁺ T cells. The mechanism deciphered for the loss of DC^Old and DC^Dysbiotic tolerance was chiefly through the overactivation of NF-κB, impaired frequency of Tregs, upregulation in the level of pro-inflammatory molecules (IL-6, IL-1β, TNF-α, IL-12, IFN-γ), and decline in the anti-inflammatory moieties (IL-10, TGF-β, IL-4, IDO, arginase, NO, IRF-4, IRF-8, PDL1, BTLA4, ALDH2). Importantly, a significant decline in the frequency of the Lactobacillus genus was noticed in the gut. Replenishing the gut of old mice with the Lactobacillus plantarum reinvigorated the tolerogenic function of DCs through the rewiring of inflammatory and metabolic pathways. Thus, for the first time, we demonstrate the impact of age-related gut dysbiosis on the loss of DC tolerance. This finding may open avenues for therapeutic intervention for treating age-associated disorders with the Lactobacillus plantarum.     

Associating somatic mutation with clinical outcomes through kernel regression and optimal transport

Somatic mutations in cancer patients are inherently sparse and potentially high dimensional. Cancer patients may share the same set of deregulated biological processes perturbed by different sets of somatically mutated genes. Therefore, when assessing the associations between somatic mutations and clinical outcomes, gene-by-gene analysis is often under-powered because it does not capture the complex disease mechanisms shared across cancer patients. Rather than testing genes one by one, an intuitive approach is to aggregate somatic mutation data of multiple genes to assess their joint association with clinical outcomes. The challenge is how to aggregate such information. Building on the optimal transport method, we propose a principled approach to estimate the similarity of somatic mutation profiles of multiple genes between tumor samples, while accounting for gene–gene similarities defined by gene annotations or empirical mutational patterns. Using such similarities, we can assess the associations between somatic mutations and clinical outcomes by kernel regression. We have applied our method to analyze somatic mutation data of 17 cancer types and identified at least five cancer types, where somatic mutations are associated with overall survival, progression-free interval, or cytolytic activity.     

Modeling an immune response to influenza A virus infection in alveolar epithelial cells

Influenza A viruses (IAV) have been the cause of several influenza pandemics in history and are a significant threat for the next global pandemic. Hospitalized influenza patients often have excess interferon production and a dysregulated immune response to the IAV infection. Obtaining a better understanding of the mechanisms of IAV infection that induce these harmful effects would help drug developers and health professionals create more effective treatments for IAV infection and improve patient outcomes. IAV stimulates viral sensors and receptors expressed by alveolar epithelial cells, like RIG-I and toll-like receptor 3 (TLR3). These two pathways coordinate with one another to induce expression of type III interferons to combat the infection. Presented here is a queuing theory-based model of these pathways that was designed to analyze the timing and amount of interferons produced in response to IAV single stranded RNA and double-stranded RNA detection. The model accurately represents biological data showing the necessary coordination of the RIG-I and TLR3 pathways for effective interferon production. This model can serve as the framework for future studies of IAV infection and identify new targets for potential treatments.     

人为噪声对动物的非听觉影响

噪声在环境中广泛存在,城市化的迅速发展也使野生动物接触到人为噪声的机会增大。越来越多的证据表明,人为噪声在许多方面影响着人类的健康以及野生动物的生存。对这些研究进行总结发现,噪声会改变动物的生理状态,使其处在较高的应激水平,进而影响动物的抗氧化能力和免疫能力,甚至使雏鸟的端粒缩短。人为噪声的存在还会影响动物的学习和认知能力,干扰动物觅食、交流等行为。这些因素累积就可能会降低动物后代的存活率,改变物种丰度,对动物的生存造成威胁。对人为噪声带来的非听觉影响的研究,有助于更全面地了解噪声的潜在危害,采取更为积极的缓解应对措施。