Development of Transplantation Immunity and Restoration Experiments in the Thymectomized Amphibian

This paper examines the thymic dependence of alloimmunity inamphibians. In Xenopus, the presence of a thymus during thefirst 2 weeks of life is essential for the development of normalfirst-set skin allograft immunity. Thymectomy during this earlyperiod always impairs the alloimmune response of young adulttoads. However, most of these thymectomized animals are ableto completely destroy skin allografts, albeit with prolongedrejection times. Chronic graft rejection, rather than tolerance,still occurs following thymectomy as early as 5 days, when thethymus contains no small lymphocytes. In contrast to the considerabledifferences in first-set allograft survival times in controland early-thymectomized Xenopus, second-set grafts, appliedsubsequent to first-set destruction, are rejected in acute fashion(<3 weeks) in both groups. That the defect in first-set alloimmunityis specifically related to absence of thymus has been confirmedby implanting allogeneic thymus 2 weeks post-thymectomy. Thedonor thymus remains healthy and restores the allograft responseto normal. In contrast, allogeneic spleen does not reconstituteand itself often undergoes destruction. Preliminary autoradiographicexperiments on lymphoid tissue involvement in first-set allograftrejection are also described.     

Stability of Microbiota Facilitated by Host Immune Regulation: Informing Probiotic Strategies to Manage Amphibian Disease

Microbial communities can augment host immune responses and probiotic therapies are under development to prevent or treat diseases of humans, crops, livestock, and wildlife including an emerging fungal disease of amphibians, chytridiomycosis. However, little is known about the stability of host-associated microbiota, or how the microbiota is structured by innate immune factors including antimicrobial peptides (AMPs) abundant in the skin secretions of many amphibians. Thus, conservation medicine including therapies targeting the skin will benefit from investigations of amphibian microbial ecology that provide a model for vertebrate host-symbiont interactions on mucosal surfaces. Here, we tested whether the cutaneous microbiota of Panamanian rocket frogs, Colostethus panamansis, was resistant to colonization or altered by treatment. Under semi-natural outdoor mesocosm conditions in Panama, we exposed frogs to one of three treatments including: (1) probiotic - the potentially beneficial bacterium Lysinibacillus fusiformis, (2) transplant – skin washes from the chytridiomycosis-resistant glass frog Espadarana prosoblepon, and (3) control – sterile water. Microbial assemblages were analyzed by a culture-independent T-RFLP analysis. We found that skin microbiota of C. panamansis was resistant to colonization and did not differ among treatments, but shifted through time in the mesocosms. We describe regulation of host AMPs that may function to maintain microbial community stability. Colonization resistance was metabolically costly and microbe-treated frogs lost 7–12% of body mass. The discovery of strong colonization resistance of skin microbiota suggests a well-regulated, rather than dynamic, host-symbiont relationship, and suggests that probiotic therapies aiming to enhance host immunity may require an approach that circumvents host mechanisms maintaining equilibrium in microbial communities.     

两栖类动物皮肤分泌物及其生物学适应意义--大蹼铃蟾皮肤分泌物蛋白质多肽组的启示

以大蹼铃蟾(Bombina maxima)为代表性物种,揭示了两栖类皮肤分泌物蛋白质多肽组丰富的分子和功能多样性。目前在大蹼铃蟾已发现的分子包括3类不同的抗菌肽、缓激肽、缓激肽增强肽和缓激肽拮抗肽、缓激肽基因相关肽、富含脯氨酸铃蟾肽及其基因相关肽、神经调节素U、Bv8肽、三叶型蛋白和蛋白酶抑制剂等。抗菌肽分子多样性及其形成机制、缓激肽及其基因相关肽功能和表达模式的多样性都较好地揭示了在多样的生态条件下,两栖类皮肤活性肽环境适应的分子基础及生物合成的调控机制。富含血红素辅基的白蛋白广泛分布在大蹼铃蟾皮肤外皮层细胞膜上和真皮海绵层内,表明它在皮肤的生理功能,如在呼吸、物质交换和渗透压调节中有重要作用。两栖类皮肤分泌物蛋白质多肽组,由于其分子结构的多样性、新颖性和哺乳类同系物的存在,在生物医学研究和天然药物开发中具有独特和不可替代的价值;同时,两栖类皮肤功能基因组具有多样性丰富、快速重组突变的特征,是探讨生物适应的基因基础、基因形成机制和进化特性等生物学基本问题的优秀模型。     

两栖类动物皮肤活性物质的利用兼论中国两栖类资源开发的策略

中国拥有丰富的两栖类动物资源,它是中国生物资源的重要组成部分,也是人类的宝贵财富,具有很大的开发利用潜力。中国对两栖类生物资源的开发利用已取得一定的成果,但还有很多不足,尤其是关于两栖类皮肤活性生物分子的研究开发工作,基本上还是一片空白。着眼于疾病治疗因子的筛选和生物活性分子的发现,对中国部分两栖类动物进行了系统的筛选研究。发现了一系列的生物活性分子和可能具临床应用价值的生物因子,并结合中国及世界两栖类资源开发利用的现状,主要从药物开发和资源保护的角度对中国两栖类资源的开发利用提出几点建议。     

Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair

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Risk Models to Predict Chronic Kidney Disease and Its Progression: A Systematic Review

Background

Chronic kidney disease (CKD) is common, and associated with increased risk of cardiovascular disease and end-stage renal disease, which are potentially preventable through early identification and treatment of individuals at risk. Although risk factors for occurrence and progression of CKD have been identified, their utility for CKD risk stratification through prediction models remains unclear. We critically assessed risk models to predict CKD and its progression, and evaluated their suitability for clinical use.

Methods and Findings

We systematically searched MEDLINE and Embase (1 January 1980 to 20 June 2012). Dual review was conducted to identify studies that reported on the development, validation, or impact assessment of a model constructed to predict the occurrence/presence of CKD or progression to advanced stages. Data were extracted on study characteristics, risk predictors, discrimination, calibration, and reclassification performance of models, as well as validation and impact analyses. We included 26 publications reporting on 30 CKD occurrence prediction risk scores and 17 CKD progression prediction risk scores. The vast majority of CKD risk models had acceptable-to-good discriminatory performance (area under the receiver operating characteristic curve>0.70) in the derivation sample. Calibration was less commonly assessed, but overall was found to be acceptable. Only eight CKD occurrence and five CKD progression risk models have been externally validated, displaying modest-to-acceptable discrimination. Whether novel biomarkers of CKD (circulatory or genetic) can improve prediction largely remains unclear, and impact studies of CKD prediction models have not yet been conducted. Limitations of risk models include the lack of ethnic diversity in derivation samples, and the scarcity of validation studies. The review is limited by the lack of an agreed-on system for rating prediction models, and the difficulty of assessing publication bias.

Conclusions

The development and clinical application of renal risk scores is in its infancy; however, the discriminatory performance of existing tools is acceptable. The effect of using these models in practice is still to be explored. Please see later in the article for the Editors'' Summary     

A Simple and Accurate Method for the Study of Water Movement across Amphibian Skin

Ethical principles have long been associated with biological phenomena. A review of some of the different forms this has taken in the past and of issues which are arising currently suggests that ethics should be taught as part of biological education within a framework of history, futures study, training in clear thinking and the development of empathy.     

Anthropogenic and Ecological Drivers of Amphibian Disease (Ranavirosis)

Ranaviruses are causing mass amphibian die-offs in North America, Europe and Asia, and have been implicated in the decline of common frog (Rana temporaria) populations in the UK. Despite this, we have very little understanding of the environmental drivers of disease occurrence and prevalence. Using a long term (1992-2000) dataset of public reports of amphibian mortalities, we assess a set of potential predictors of the occurrence and prevalence of Ranavirus-consistent common frog mortality events in Britain. We reveal the influence of biotic and abiotic drivers of this disease, with many of these abiotic characteristics being anthropogenic. Whilst controlling for the geographic distribution of mortality events, disease prevalence increases with increasing frog population density, presence of fish and wild newts, increasing pond depth and the use of garden chemicals. The presence of an alternative host reduces prevalence, potentially indicating a dilution effect. Ranavirosis occurrence is associated with the presence of toads, an urban setting and the use of fish care products, providing insight into the causes of emergence of disease. Links between occurrence, prevalence, pond characteristics and garden management practices provides useful management implications for reducing the impacts of Ranavirus in the wild.     

Prior Infection Does Not Improve Survival against the Amphibian Disease Chytridiomycosis

Many amphibians have declined globally due to introduction of the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Hundreds of species, many in well-protected habitats, remain as small populations at risk of extinction. Currently the only proven conservation strategy is to maintain species in captivity to be reintroduced at a later date. However, methods to abate the disease in the wild are urgently needed so that reintroduced and wild animals can survive in the presence of Bd. Vaccination has been widely suggested as a potential strategy to improve survival. We used captive-bred offspring of critically endangered booroolong frogs (Litoria booroolongensis) to test if vaccination in the form of prior infection improves survival following re exposure. We infected frogs with a local Bd isolate, cleared infection after 30 days (d) using itraconazole just prior to the onset of clinical signs, and then re-exposed animals to Bd at 110 d. We found prior exposure had no effect on survival or infection intensities, clearly showing that real infections do not stimulate a protective adaptive immune response in this species. This result supports recent studies suggesting Bd may evade or suppress host immune functions. Our results suggest vaccination is unlikely to be useful in mitigating chytridiomycosis. However, survival of some individuals from all experimental groups indicates existence of protective innate immunity. Understanding and promoting this innate resistance holds potential for enabling species recovery.     

帕金森病中铁与Alpha-突触核蛋白的相互作用

帕金森病(Parkinson's disease,PD)的特异标志物Alpha-突触核蛋白的异常聚集往往伴有铁的沉积,说明铁与Alpha-突触核蛋白聚集之间存在一定联系。铁可以通过增加Alpha-突触核蛋白的产生及抑制其降解从而促进Alpha-突触核蛋白聚集。Alpha-突触核蛋白作为一种高铁还原酶也可以影响细胞铁的代谢。本文就铁与Alpha-突触核蛋白参与PD的发病以及两者之间相互作用的机制进行综述。     

Marital Quality and Stress in Pregnancy Predict the Risk of Infectious Disease in the Offspring: The Norwegian Mother and Child Cohort Study

Objectives

The aim of this study was to explore the degree to which couples’ relationship dissatisfaction and stressful life events during pregnancy predict the risk of infectious disease in the offspring during their first year of life.

Methods

Data were obtained from the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health. Pregnant women completed questionnaires in week 30 of pregnancy concerning the couples’ relationship satisfaction and stressful life events. In follow-up questionnaires, the women reported whether their children (n = 74,801) had been subject to various categories of infectious disease: the common cold, throat infection, bronchitis, RS virus, pneumonia, pseudocroup, gastric flu, ear infection, conjunctivitis and urinary tract infection. Reports from two age groups of infants were used. Associations between the predictor and outcome variables were assessed via logistic regression and linear regression analyses.

Results

Separate logistic regression analyses for each disease and age group showed that prenatal relationship dissatisfaction and stressful life events were significantly associated with all reported categories of infectious disease. After controlling for socioeconomic factors, social support, smoking, breastfeeding, maternal depression, the sex of the offspring, and use of child care, 29 out of 32 tested associations were statistically significant. Finally, multivariate linear regression analyses showed that prenatal relationship dissatisfaction and stressful life events were significantly associated with the frequency, as well as the variety, of infectious disease in the offspring.     

The Neuro-Hormonal Control of Rapid Dynamic Skin Colour Change in an Amphibian during Amplexus

Sexual signalling using dynamic skin colouration is a key feature in some vertebrates; however, it is rarely studied in amphibians. Consequently, little is known about the hormonal basis of this interesting biological phenomenon for many species. Male stony creek frogs (Litoria wilcoxii) are known to change dorsal colouration from brown to lemon yellow within minutes. This striking change is faster then what has been seen most amphibians, and could therefore be under neuronal regulation, a factor that is rarely observed in amphibians. In this study, we observed colour changes in wild frogs during amplexus to determine the natural timing of colour change. We also investigated the hypothesis that colour change is mediated by either reproductive or neuro- hormones. This was achieved by injecting frogs with epinephrine, testosterone, saline solution (control 1) or sesame oil (control 2). A non-invasive approach was also used wherein hormones and controls were administered topically. Male frogs turned a vivid yellow within 5 minutes of initiation of amplexus and remained so for 3–5 hours before rapidly fading back to brown. Epinephrine-treated frogs showed a significant colour change from brown to yellow within 5 minutes, however, testosterone-treated frogs did not change colour. Our results provide evidence of the role neuronal regulation plays in colour change systems.