BACKGROUND & AIMS: :Extensive laboratory testing is often performed in the emergency department evaluation of the new-onset seizure patient. To determine the utility of such testing, a prospective study of patients with a new-onset seizure presenting to the ED of an inner-city, university-affiliated teaching hospital was done. One hundred thirty-six patients were entered into the study between October 1984 and January 1988. All patients had uniform data collection performed. Pertinent historical information and physical examination findings were recorded on a standardized form before laboratory abnormality was a sole or contributory cause of the seizure disorder. These included four patients with hypoglycemia, four with hyperglycemia, two with hypocalcemia, and one with hypomagnesemia. Only two cases (hypoglycemia) were not suspected on the basis of findings on the history or physical examination. In ED patients, the incidence of a new-onset seizure due to a correctable metabolic disturbance is low. We conclude that, with the exception of the serum glucose, the extensive ED laboratory workup often done for the evaluation of a new-onset seizure is unnecessary. Further test ordering should be directed by the medical history and physical examination.

背景与目标： ：急诊科通常会对新发作的癫痫患者进行广泛的实验室检查。为了确定此类测试的实用性，对在市内大学附属教学医院急诊室就诊的新发癫痫患者进行了一项前瞻性研究。在1984年10月至1988年1月之间，共有136例患者进入研究。所有患者均进行了统一的数据收集。在实验室异常是癫痫发作的唯一或共同原因之前，以标准化的形式记录相关的历史信息和体格检查结果。这些患者包括四名低血糖患者，四名高血糖患者，两名低钙血症患者和一名低镁血症患者。根据病史或体格检查的结果，仅怀疑2例（低血糖）。在ED患者中，由于可纠正的代谢紊乱引起的新发作癫痫发作的发生率较低。我们得出的结论是，除血清葡萄糖外，不必要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的测试顺序应由病史和体格检查指示。

BACKGROUND & AIMS: PURPOSE:The diagnostic assessment and prognostic value of the posterior ligamentous complex (PLC) remains a controversial topic in the management of patients with thoracolumbar spinal injury. The purpose of this review was to critically appraise the literature and present an overview of the: (1) precision, (2) accuracy, and (3) validity of detecting PLC injuries in patients with thoracic and lumbar spine trauma. METHODS:Studies evaluating the precision, accuracy and/or validity of detecting and managing PLC injuries in patients with thoracic and/or lumbar spine injuries were searched through the Medline database (1966 to September 2011). References were retrieved and evaluated individually and independently by two authors. RESULTS:Twenty-one eligible studies were identified. Few studies reported the use of countermeasures for sampling and measurement bias. In nine agreement studies, the PLC was assessed in various ways, ranging from use of booklets to a complete set of diagnostic imaging. Inter-rater and intra-rater kappa values ranged from 0.188 to 0.915 and 0.455 to 0.840, respectively. In nine accuracy studies, magnetic resonance (MR) imaging was most often (n = 6) compared with intra-operative findings. In general, MR imaging tended to demonstrate relatively high negative predictive values and relatively low positive predictive values for PLC injuries. CONCLUSIONS:A wide variety of methods have been applied in the evaluation of precision and accuracy of PLC injury detection, leaving spinal surgeons with a multitude of variable results. There is scant clinical evidence demonstrating the true prognostic value of detected PLC injuries in patients with thoracic and lumbar spine injuries. We recommend the conduct of longitudinal clinical follow-up studies on those cases assessed for precision and/or accuracy of PLC injuries.

背景与目标： 目的：后韧带复合体（PLC）的诊断评估和预后价值在胸腰椎脊柱损伤患者的治疗中仍然是一个有争议的话题。这篇综述的目的是对文献进行严格的评估，并对以下方面进行概述：（1）准确性，（2）准确性和（3）在胸椎和腰椎创伤患者中检测PLC损伤的有效性。
方法：通过Medline数据库（1966年至2011年9月），对评估对胸椎和/或腰椎损伤患者进行PLC损伤检测和处理的准确性，准确性和/或有效性进行评估的研究。两位作者分别和独立检索和评价了参考文献。
结果：鉴定出二十一项符合条件的研究。很少有研究报告对抽样和测量偏差使用对策。在九项协议研究中，以各种方式对PLC进行了评估，从使用手册到完整的诊断成像。评定者间和评定者内kappa值的范围分别为0.188至0.915和0.455至0.840。在9项准确性研究中，与术中发现相比，磁共振（MR）成像频率最高​​（n = 6）。通常，MR成像倾向于表现出相对较高的PLC损伤阴性预测值和相对较低的阳性预测值。
结论：各种各样的方法已被用于PLC损伤检测的准确性和准确性的评估，使脊柱外科医师具有多种多样的结果。几乎没有临床证据证明所检测到的PLC损伤对胸椎和腰椎损伤患者具有真正的预后价值。我们建议对那些评估PLC损伤的准确性和/或准确性的病例进行纵向临床随访研究。

BACKGROUND & AIMS: Objective:To estimate the cumulative incidence of persistent arthralgia at 6 months from acute Chikungunya virus (CHIKV) infection and to evaluate the association of clinical markers with the risk of long-term arthralgia. Methods:This multicenter retrospective cohort study was conducted in the Mexican state of Colima. A total of 136 individuals aged 15 years and older with serologically confirmed CHIKV infection were enrolled. Participants were interviewed at 6 months from the onset of symptoms, and self-reported persistent arthralgia (PA) was the main binary outcome. A self-report numeric rating scale (NRS) ranging from 0 to 10 was used to estimate the severity of articular pain. Results:The cumulative incidence of PA was 41.9%. Severe pain (NRS ≥ 7) presented in 36.8% of participants with PA. In multiple analysis, individuals aged 40 years and older (risk ratio (RR) = 1.60; 95% confidence interval (CI), 1.03-2.48) and those with articular pain at 3 months post-infection (RR = 3.95; 95% CI, 1.95-8.01) had a significantly increased risk of PA at 6 months from CHIKV infection. Conclusions:To the best of our knowledge, this is first report of a CHIKV-associated long-term outcome in Mexico, where the incidence of the infection has been high. This is also the first study in Latin America evaluating several factors associated with the risk of PA. Our findings may be useful in health care settings to stratify the risk of chronic arthralgia secondary to CHIKV infection and to identify patients who would benefit clinically from early medical intervention.

背景与目标： 目的：评估急性基孔肯雅病毒（CHIKV）感染六个月后持续性关节痛的累积发生率，并评估临床标志物与长期关节痛风险之间的关系。
方法：这项多中心回顾性队列研究在墨西哥科利马州进行。共有136位年龄在15岁及以上且经血清学证实为CHIKV感染的患者入组。从出现症状开始的六个月就对参与者进行了采访，自我报告的持续性关节痛（PA）是主要的二元结局指标。使用自我报告的数字评分量表（NRS），范围从0到10，以评估关节痛的严重程度。
结果：PA的累积发生率为41.9％。严重疼痛（NRS≥7）在PA参与者中占36.8％。在多重分析中，年龄在40岁以上（风险比（RR）= 1.60； 95％置信区间（CI），1.03-2.48）以及感染后3个月时出现关节痛的患者（RR = 3.95； 95％CI） ，1.95-8.01）在CHIKV感染后6个月时患PA的风险显着增加。
结论：据我们所知，这是墨西哥CHIKV相关的长期结局的首次报道，该国的感染发生率很高。这也是拉丁美洲首次评估与PA风险相关的几个因素的研究。我们的发现可能在医疗机构中有用，以对继发于CHIKV感染的慢性关节痛的风险进行分层，并确定可从早期医疗干预中受益的患者。

BACKGROUND & AIMS: BACKGROUND:Laboratory animal workers are at high risk of developing occupational allergy. Little is known about the relationship between levels of exposure and the risk of developing laboratory animal allergy. Since laboratory animal work comprises a large number of different-often short lasting-tasks, it is of interest to assess which activities are associated with high, low or intermediate levels of allergen exposure. OBJECTIVE:To develop and evaluate highly sensitive immunoassays in order to quantify rat and mouse urinary allergens in airborne dust sampled during short-lasting tasks. METHODS:Personal air dust samples were taken during full-shift periods as well as during specific tasks in seven laboratory animal facilities. Two sandwich enzyme immunoassays were developed, using rabbit antisera against rat and mouse urinary proteins. The rabbit antibodies were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting and compared with IgE antibodies from sensitized laboratory animal workers. RESULTS:The rabbit antibodies were highly specific for rat and mouse urinary proteins and reacted with all IgE-binding allergens in either urinary protein preparation. The assays for rat and mouse urine were very sensitive, with detection limits of 0.075 ng/mL. The coefficient of variation of the analysis was 12.9% for both assays. Animal caretakers appeared to experience the highest exposure to aeroallergens. A large variation in exposure within jobs was found, due to differences between tasks performed during the sampling day and the facility worked at. The highest exposure levels were found during removal of contaminated bedding from the cages. However, rat and mouse allergen exposure levels during this task varied enormously between facilities, 1.1-158 ng eq/m3 and 0.63-2000 ng eq/m3, respectively. CONCLUSION:Both sandwich immunoassays are highly specific and sensitive and are able to identity tasks of relatively short duration with high, medium and low exposure to airborne rat and mouse urinary allergens.

背景与目标： 背景：实验室动物工作者有发展职业过敏的高风险。关于暴露水平与发生实验动物过敏的风险之间的关系知之甚少。由于实验室动物工作包括大量不同的，通常是短期的任务，因此评估哪些活动与高，低或中等水平的过敏原暴露相关是很有意义的。
目的：开发和评估高度敏感的免疫分析方法，以定量在短期任务中采样的空气中粉尘中的大鼠和小鼠尿液过敏原。
方法：在全班工作期间以及在特定任务期间，在七个实验室动物设施中采集了个人空气尘埃样本。使用针对大鼠和小鼠尿蛋白的兔抗血清，开发了两种夹心酶免疫测定法。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）和免疫印迹分析兔抗体，并将其与来自敏化实验动物工作者的IgE抗体进行比较。
结果：兔抗体对大鼠和小鼠的尿蛋白具有高度特异性，并与两种尿蛋白制剂中的所有IgE结合过敏原反应。大鼠和小鼠尿液的测定非常敏感，检出限为0.075 ng / mL。两种测定的分析变异系数均为12.9％。动物看护者似乎经历了最高的空气过敏原暴露。由于在采样日执行的任务与所使用的设施之间存在差异，因此发现工作中的暴露程度存在很大差异。从笼子中取出受污染的被褥时发现了最高暴露水平。但是，在此任务期间，大鼠和小鼠的过敏原暴露水平在设施之间的差异很大，分别为1.1-158 ng eq / m3和0.63-2000 ng eq / m3。
结论：这两种夹心免疫测定法都具有高度特异性和敏感性，能够识别持续时间相对较短，高，中和低暴露于机载大鼠和小鼠尿液变应原的任务。

BACKGROUND & AIMS: :Spontaneous and sound-evoked single-unit activity was recorded from afferent neurones in the cochlear ganglion of the anaesthetized pigeon. The histogram of successive intervals of spontaneous activity of 51% of neurones exhibited more short intervals than expected from a Poisson point-process description of spike times; for another 43% of neurones the point-process was Poisson. A model of spike generation was developed to account for the concentration of short spike-intervals. The proposed model contains inhibitory postsynaptic potentials at the afferent dendrite, in addition to the excitatory postsynaptic potentials. Not only does the model reproduce the first-order interval statistics of neural activity, but it provides a mechanism for improving phase-locking to the fundamental frequency of a sinusoid, and also offers an explanation for the presence of reciprocal synapses in the human cochlea.

背景与目标： ：从麻醉鸽子的耳蜗神经节传入神经元记录了自发和发声的单单位活动。 51％的神经元自发活动的连续间隔的直方图显示的间隔比根据尖峰时间的Poisson点过程描述所预期的要短。对于另外43％的神经元，点过程是泊松。开发了尖峰生成模型来说明短尖峰间隔的集中。所提出的模型除兴奋性突触后电位外，还包含传入树突处的抑制性突触后电位。该模型不仅可以再现神经活动的一阶间隔统计信息，而且还提供了一种机制，可以改善对正弦波基频的锁相，还可以解释人耳蜗中是否存在相互的突触。

BACKGROUND & AIMS: STUDY OBJECTIVES:To determine the total number of active sleep laboratories in the United States and the number of polysomnograms conducted on a yearly basis in these laboratories. METHODS:All members of the AASM and all AASM accredited sleep laboratory directors received a questionnaire addressing their laboratory and its volume. In three states, multiple telephone calls to AASM members were used to correctly identify the absolute number of labs and their PSG volume in those states. Extrapolating from the number of labs studies identified per questionnaire relative to the correct number (per calls) in those states and, then applying this ratio to the entire US, the total number of labs and studies was determined. RESULTS:Our data suggests that there are, in the year 2001, 1,292 sleep laboratories conducting 1,165,135 polysomnograms per year. This comes to 427 PSG's/year per 100,000 population in the United States. CONCLUSIONS:These data suggest that there are a relatively large number of sleep laboratories in the US conducting a substantial number of PSG's. However, there was considerable variability in this volume between states that did not relate to known markers of healthcare utilization. These numbers have likely increased since 2001.

背景与目标： 研究目的：确定美国活跃睡眠实验室的总数以及这些实验室每年进行的多导睡眠图的数量。
方法：所有AASM成员和所有AASM认可的睡眠实验室主任均收到了一份有关其实验室及其数量的问卷。在三个州中，使用多次致电AASM成员的电话来正确标识实验室的绝对数量及其在这些州中的PSG量。从每个调查表中确定的实验室研究数量相对于这些州的正确数量（每次呼叫）进行推断，然后将该比率应用于整个美国，即可确定实验室和研究的总数。
结果：我们的数据表明，在2001年，有1,292个睡眠实验室每年进行1,165,135项睡眠监测。在美国，每10万人中有427个PSG /年。
结论：这些数据表明，美国有相对大量的睡眠实验室在进行大量的PSG。但是，与已知的医疗保健利用指标无关，各州之间的容积存在很大差异。自2001年以来，这些数字可能有所增加。

BACKGROUND & AIMS: :It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals' performance in behavioral tests that often accompany acute and chronic seizure testing.

背景与目标： ：越来越清楚的是，即使是近交系的小鼠和大鼠的遗传背景，也可能对癫痫发作易感性和癫痫的测量产生深远的影响。这些差异可以通过基因作图研究加以利用，以揭示对癫痫和癫痫病重要的基因。然而，转基因动物的品系背景，尤其是混合遗传背景，在品系的选择以及结果和结论的解释中都需要仔细考虑。例如，取决于背景株，具有与癫痫有关的基因的靶向缺失的小鼠可具有完全不同的表型。在这篇综述中，我们讨论了与这种遗传异质性如何以及在癫痫领域中如何利用有关的发现，以揭示癫痫和癫痫的新见解。此外，我们讨论了如何在啮齿动物品系甚至动物供应商选择方面需要谨慎，以及这如何以意想不到的方式显着影响癫痫发作和癫痫发作参数。这在决定用于产生具有针对性基因缺失的小鼠的选择品系的决定中尤其重要。最后，我们讨论了环境（在供应商和/或实验室）的作用以及表观遗传因素对菌株间和菌株间差异的影响，以及这种差异如何影响癫痫发作的表达以及动物在行为测试中通常伴随着急性和慢性癫痫发作的表现测试。

BACKGROUND & AIMS: :Visual sensitivity is comprehensively described by the contrast sensitivity function (CSF), but current routine clinical care does not include its assessment because of the time-consuming need to estimate thresholds for a large number of spatial frequencies. The quick CSF method, however, dramatically reduces testing times by using a Bayesian information maximization rule. We evaluate the test-retest variability of a tablet-based quick CSF implementation in a study with 100 subjects who repeatedly assessed their vision with and without optical correction. We first discuss two commonly used measures of repeatability, intraclass correlation and the Bland-Altman Coefficient of Repeatability, and show that they are vulnerable to artifacts. Instead, we propose to formulate precision as an information retrieval task: from all repeat test scores, can we retrieve a certain individual based on their first test score? We then use rank-based analyses such as mean average precision as a better measure to compare different test metrics, and show that the highest test-retest precision is achieved using a summary statistic, the area under the log CSF (AULCSF). This demonstrates the benefit of assessment of the whole CSF compared to sensitivity at individual spatial frequencies only. AULCSF also yields best discrimination performance (99.2%) between measurements that were taken with and without glasses, respectively, even better than CSF Acuity. The tablet-based quick CSF thus enables the rapid and reliable home monitoring of visual function, which has the potential to improve early diagnosis and treatment of ophthalmic pathologies such as diabetic retinopathy or age-related macular degeneration.

背景与目标： ：视觉敏感度由对比敏感度功能（CSF）进行了全面描述，但是当前的常规临床护理不包括其评估，因为需要花费大量时间来估计大量空间频率的阈值。但是，快速的CSF方法通过使用贝叶斯信息最大化规则大大减少了测试时间。我们在一项包含100名受试者的研究中评估了基于平板电脑的快速CSF实施的重测变异性，这些受试者在有无光学矫正的情况下反复评估了他们的视力。我们首先讨论两种可重复性的常用度量，类内相关性和可重复性的Bland-Altman系数，并表明它们易受伪影的影响。相反，我们建议将精确度公式化为信息检索任务：从所有重复的考试成绩中，我们是否可以根据他们的第一个考试成绩来检索某个人？然后，我们使用基于等级的分析（例如平均平均精度）作为比较不同测试指标的更好方法，并显示使用汇总统计量（对数CSF下的面积（AULCSF））可以实现最高的重测精度。与仅在单个空间频率下的灵敏度相比，这证明了评估整个CSF的益处。在分别戴有眼镜和不戴眼镜的情况下，AULCSF还可产生最佳的辨别性能（99.2％），甚至优于CSF Acuity。因此，基于平板电脑的快速CSF可以实现对视觉功能的快速可靠的家庭监控，具有改善早期诊断和治疗眼科疾病（如糖尿病性视网膜病或年龄相关性黄斑变性）的潜力。

BACKGROUND & AIMS: :Various factors, including the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling, have generated the need for new solutions to the ever-increasing worldwide dilemma of substance testing. This review provides a historical sketch on the accentuation of this dilemma, and highlights fundamental limitations to the countermeasures taken so far. It describes the potential of recently-introduced microsystems to emulate human organs in 'organ-on-a-chip' devices. Finally, it focuses on an in-depth analysis of the first devices that aimed to mimic human systemic organ interactions in 'human-on-a-chip' systems. Their potential to replace acute systemic toxicity testing in animals, and their inability to provide alternatives to repeated dose long-term testing, are discussed. Inspired by the latest discoveries in human biology, tissue engineering and micro-systems technology, this review proposes a paradigm shift to overcome the apparent challenges. A roadmap is outlined to create a new homeostatic level of biology in 'human-on-a-chip' systems in order to, in the long run, replace systemic repeated dose safety evaluation and disease modelling in animals.

背景与目标： ：各种因素，包括实验室动物与人类之间的系统发育距离，当前体外系统与人体之间的差异以及计算机模拟的局限性，都导致需要新的解决方案来应对全球范围内日益加剧的物质困境测试。这次审查提供了关于这一困境加深的历史速写，并着重指出了迄今为止采取的对策的基本局限性。它描述了最近引入的微系统在“片上器官”设备中模拟人体器官的潜力。最后，它着重于对旨在模仿“芯片上人”系统中人体系统器官相互作用的首批设备的深入分析。讨论了其替代动物急性全身毒性试验的潜力，以及它们无法提供重复剂量长期试验的替代方法。受到人类生物学，组织工程和微系统技术的最新发现的启发，本综述提出了一种范式转变，以克服这些明显的挑战。概述了一个路线图，以在“单芯片人”系统中创建新的体内稳态生物学水平，以便从长远来看取代动物的系统性重复剂量安全性评估和疾病建模。

BACKGROUND & AIMS: :Transparent exopolymer particles (TEP) are a class of marine gel particles and important links between surface ocean biology and atmospheric processes. Derived from marine microorganisms, these particles can facilitate the biological pumping of carbon dioxide to the deep sea, or act as cloud condensation and ice nucleation particles in the atmosphere. Yet, environmental controls on TEP abundance in the ocean are poorly known. Here, we investigated some of these controls during the first multiyear time-series on TEP abundance for the Fram Strait, the Atlantic gateway to the Central Arctic Ocean. Data collected at the Long-Term Ecological Research observatory HAUSGARTEN during 2009 to 2014 indicate a strong biological control with highest abundance co-occurring with the prymnesiophyte Phaeocystis pouchetii. Higher occurrence of P. pouchetii in the Arctic Ocean has previously been related to northward advection of warmer Atlantic waters, which is expected to increase in the future. Our study highlights the role of plankton key species in driving climate relevant processes; thus, changes in plankton distribution need to be accounted for when estimating the ocean's biogeochemical response to global change.

背景与目标： ：透明的外聚合物颗粒（TEP）是一类海洋凝胶颗粒，是海洋表面生物学与大气过程之间的重要纽带。这些微粒源自海洋微生物，可促进二氧化碳向深海的生物泵送，或在大气中充当云凝结和冰核形核的微粒。然而，对海洋中TEP丰度的环境控制知之甚少。在这里，我们调查了Fram海峡（通往中北冰洋的大西洋门户）的TEP丰度的第一个多年期序列中的一些控制措施。长期生态研究天文台HAUSGARTEN在2009年至2014年期间收集的数据表明，与褐藻类植物Phaeocystis pouchetii共同出现的生物控制力最高。在北冰洋，Pouchetii的高发以前与大西洋较温暖的水域向北平流有关，预计将来还会增加。我们的研究强调了浮游生物关键物种在驱动气候相关过程中的作用；因此，在估算海洋对全球变化的生物地球化学反应时，必须考虑浮游生物分布的变化。

BACKGROUND & AIMS: :Fungi produce a variety of secondary metabolites (SMs), low-molecular weight compounds associated with many potentially useful biologic activities. The examples of biotechnologically relevant fungal metabolites include penicillin, a β-lactam antibiotic, and lovastatin, a cholesterol-lowering drug. The discovery of pharmaceutical lead compounds within the microbial metabolic pools relies on the selection and biochemical characterization of promising strains. Not all SMs are produced under standard cultivation conditions, hence the uncovering of chemical potential of investigated strains often requires the use of induction strategies to awake the associated biosynthetic genes. Triggering the secondary metabolic pathways can be achieved through the variation of cultivation conditions and growth media composition. The alternative strategy is to use genetic engineering to activate the respective genomic segments, e.g. by the manipulation of regulators or chromatin-modifying enzymes. Recently, whole-genome sequencing of several fungi isolated from the Chernobyl accident area was reported by Singh et al. (Genome Announc 2017; 5:e01602-16). These strains were selected for exposure to microgravity at the International Space Station. Biochemical characterization of fungi cultivated under extreme conditions is likely to provide valuable insights into the adaptation mechanism associated with metabolism and, possibly, a catalog of novel molecules of potential pharmaceutical importance.

背景与目标： ：真菌产生多种次级代谢产物（SMs），低分子量化合物，与许多潜在有用的生物活性有关。与生物技术相关的真菌代谢物的例子包括青霉素（一种β-内酰胺抗生素）和洛伐他汀（一种降低胆固醇的药物）。在微生物代谢池中发现药物先导化合物依赖于有前途的菌株的选择和生化特性。并非所有SM都是在标准培养条件下生产的，因此要揭示被调查菌株的化学潜能，通常需要使用诱导策略来唤醒相关的生物合成基因。触发次级代谢途径可以通过改变培养条件和生长培养基组成来实现。另一种策略是使用基因工程来激活各自的基因组片段，例如通过调节剂或染色质修饰酶的操作。最近，Singh等报道了从切尔诺贝利事故地区分离出的几种真菌的全基因组测序。 （Genome Announc 2017; 5：e01602-16）。这些菌株被选择在国际空间站暴露于微重力中。在极端条件下培养的真菌的生化特性可能会提供与代谢相关的适应机制的有价值的见解，并可能提供具有潜在药物重要性的新型分子的目录。

BACKGROUND & AIMS: :Brucella species are pathogenic agents that cause brucellosis, a debilitating zoonotic disease that affects a large variety of domesticated animals and humans. Brucella melitensis and Brucella abortus are considered major health threats because of their highly infectious nature and worldwide occurrence. The availability of the annotated genomes for these two species has allowed a comparative proteomics study of laboratory grown B. melitensis 16M and B. abortus 2308 by two-dimensional (2-D) gel electrophoresis and peptide mass fingerprinting. Computer-assisted analysis of the different 2-D gel images of strains 16M and 2308 revealed significant quantitative and qualitative differences in their protein expression patterns. Proteins involved in membrane transport, particularly the high affinity amino acids binding proteins, and those involved in Sec-dependent secretion systems related to type IV and type V secretion systems, were differentially expressed. Differential expression of these proteins may be responsible for conferring specific host preference in the two strains 2308 and 16M.

背景与目标： 布鲁氏菌属是引起布鲁氏菌病的病原体，布鲁氏菌病是一种使人畜共患的令人衰弱的人畜共患疾病，影响多种驯养的动物和人类。布鲁氏菌和流产布鲁氏菌被认为是主要的健康威胁，因为它们具有高度的传染性和在世界范围内广泛存在。这两个物种的注释基因组的可获得性允许通过二维（2-D）凝胶电泳和肽质量指纹图谱对实验室生长的B. melitensis 16M和B.abortus 2308进行蛋白质组学比较研究。对菌株16M和2308的不同2-D凝胶图像的计算机辅助分析显示，它们的蛋白质表达模式存在明显的定量和定性差异。差异表达了膜运输中涉及的蛋白质，特别是高亲和力氨基酸结合蛋白，以及涉及与IV型和V型分泌系统有关的Sec依赖性分泌系统的蛋白质。这些蛋白质的差异表达可能是在两个菌株2308和16M中赋予特定宿主偏好的原因。

BACKGROUND & AIMS: :In ectotherms, lower temperatures in high-latitude environments would theoretically reduce the annual growth rates of individuals. If slower growth and resultant smaller body size reduce fitness, individuals in higher latitudes may evolve compensatory responses. Two alternative models of such latitudinal compensation are possible: Model I: thermal reaction norms for growth rates of high-latitude individuals may be horizontally shifted to a lower range of temperatures, or Model II: reaction norms may be vertically shifted so that high-latitude individuals can grow faster across all temperatures. Model I is expected when annual growth rates in the wild are only a function of environmental temperatures, whereas Model II is expected when individuals in higher latitudes can only grow during a shorter period of a year. A variety of mixed strategies of these two models are also possible, and the magnitude of horizontal versus vertical variation in reaction norms among latitudinal populations will be indicative of the importance of "temperature" versus "seasonality" in the evolution of latitudinal compensation. However, the form of latitudinal compensation may be affected by possible genetic constraints due to the genetic architecture of reaction norms. In this study, we examine the inter- and intrapopulation variations in thermal reaction norms for growth rate of the medaka fish Oryzias latipes. Common-environment experiments revealed that average reaction norms differed primarily in elevation among latitudinal populations in a manner consistent with Model II (adaptation to "seasonality"), suggesting that natural selection in high latitudes prefers individuals that grow faster even within a shorter growing season to individuals that have longer growing seasons by growing at lower temperatures. However, intrapopulation variation in reaction norms was also vertical: some full-sibling families grew faster than others across all temperatures examined. This tendency in intrapopulation genetic variation for thermal reaction norms may have restricted the evolution of latitudinal compensation, irrespective of the underlying selection pressure.

背景与目标： ：在等温线中，高纬度环境中的低温理论上会降低个人的年增长率。如果较慢的生长和由此产生的较小的体型降低了适应性，则高纬度地区的人们可能会出现代偿性反应。这种纬度补偿的两个替代模型是可能的：模型I：高纬度个体生长速率的热反应规范可以水平移动到较低的温度范围，或者模型II：反应规范可以垂直移动以使高纬度个人可以在所有温度下更快地成长。当野外的年增长率仅是环境温度的函数时，可以预期为模型I，而当纬度较高的人只能在较短的一年内增长时，则可以预测为模型II。这两种模型的多种混合策略也是可能的，并且在纬度种群之间反应规范的水平相对于垂直变化的大小将指示“温度”相对于“季节性”在纬度补偿演变中的重要性。但是，由于反应规范的遗传结构，纬度补偿的形式可能会受到可能的遗传约束的影响。在这项研究中，我们研究了aka对印度med鱼Oryzias latipes生长速度的热反应规范中的种群间和种群内变化。共同环境实验表明，平均反应规范主要在纬度种群之间以与II型一致（适应“季节性”）的方式不同，这表明高纬度地区的自然选择更倾向于即使在较短的生长季节中生长速度更快的个体，也不符合模型II的要求。生长在较低温度下的生长季节较长的个体。但是，种群内反应规范的变化也是垂直的：在所有考察的温度范围内，一些全兄弟家庭的生长速度快于其他家庭。无论潜在的选择压力如何，热反应范围内种群遗传变异的这种趋势都可能限制了纬度补偿的演变。

BACKGROUND & AIMS: :We compared serotype distributions of Streptococcus pneumoniae isolates from patients aged <5 and o5 years with invasive pneumococcal disease in New South Wales, Australia, and antibiotic susceptibilities of isolates from the <5 years age group only, before (2002–2004) and after(2005–2009) introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Overall, there were significant decreases in the mean annual number of referred isolates (770 vs. 515) and the proportion belonging to PCV7 serotypes (74% vs. 38%), but non-PCV7 serotypes, particularly 19A, increased (5% vs. 18%). All changes were more marked in the <5 years age group.Susceptibility testing of isolates from the <5 years age group showed variation in resistance between serotypes, but significant overall increases in penicillin non-susceptibility (23% vs. 31%),ceftriaxone resistance (2% vs. 12%) and multidrug resistance (4% vs. 7%) rates ; erythromycin resistance fell (32% vs. 25%). Continued surveillance is needed to monitor changes following the introduction of 13-valent PCV in 2012.

背景与目标： ：我们比较了澳大利亚新南威尔士州<5和o5岁患有侵袭性肺炎球菌疾病的患者的肺炎链球菌分离株的血清型分布和仅<5岁年龄组的分离株的抗生素敏感性（2002-2004年之前和之后） （2005-2009）引入了7价肺炎球菌结合疫苗（PCV7）。总体而言，转介的分离株的年均数量显着减少（770比515）和属于PCV7血清型的比例（74％比38％），但非PCV7血清型，特别是19A血清型增加（5％vs。 18％）。在<5岁年龄组中所有变化均更为明显。<5岁年龄组的分离株的药敏试验显示，血清型之间的耐药性存在差异，但青霉素的非药敏性总体显着增加（23％vs. 31％），头孢曲松耐药率（2％vs. 12％）和多药耐药性（4％vs. 7％）比率；红霉素耐药性下降（32％对25％）。在2012年推出13价PCV之后，需要持续进行监测以监测变化。

BACKGROUND & AIMS: :During the production of clinical-grade retroviral vector supernatant, we noted significant differences in the lactate production and glucose consumption of various producer cell lines submitted to the National Gene Vector Laboratory (NGVL). Since differences in growth characteristics could be important in determining the optimal culture conditions for maximizing titer, we studied the growth characteristics of three commonly used packaging cell lines: PA317, PG13 and GP+envAM12. A transformed phenotype, assessed by the ability to form colonies in semisolid media, was evident in all three packaging cell lines tested. In confluent cultures, the rates of glucose consumption and lactate production (per cell per hour) were similar for the three lines tested, but the growth rate and culture density varied. PA317 and PG13 continued to expand after reaching confluence, resulting in higher cell densities and subsequent rapid depletion of glucose within the 24-hr observation period. When the cell lines were evaluated for titer optimization, the slower growing packaging cell line GP+envAM12 generally provided the highest titer after 8 hr of culture in confluent roller bottles, while most vectors introduced into PA317 and PG13 cells yielded optimal titers after 24 hr of culture. We also found that the improved titers obtained by culturing cells at 32 degrees C previously reported for PA317 cells do not apply to other packaging cell lines. In particular, PG13 rapidly lost titer when grown at the lower temperature. Our findings suggest that optimization of titer requires careful consideration of the culture conditions, which should be individualized for the vector producer cell line.

背景与目标： 在临床级逆转录病毒载体上清液的生产过程中，我们注意到提交给国家基因载体实验室（NGVL）的各种生产细胞系的乳酸生产和葡萄糖消耗存在显着差异。由于生长特性的差异对于确定最大滴度的最佳培养条件可能很重要，因此我们研究了三种常用包装细胞系的生长特性：PA317，PG13和GP envAM12。通过在半固体培养基中形成菌落的能力评估的转化表型在所有测试的三种包装细胞系中均很明显。在融合培养物中，三个试验品系的葡萄糖消耗速率和乳酸产生速率（每细胞每小时）相似，但是生长速率和培养密度不同。达到汇合后，PA317和PG13继续扩增，导致更高的细胞密度，随后在24小时观察期内葡萄糖迅速耗竭。当评估细胞系的滴度优化时，生长缓慢的包装细胞系GP envAM12在融合滚瓶中培养8小时后通常提供最高滴度，而导入PA317和PG13细胞的大多数载体在培养24小时后产生最佳滴度。我们还发现先前报道的PA317细胞通过在32摄氏度下培养细胞获得的改进的滴度不适用于其他包装细胞系。特别是，PG13在较低温度下生长时会迅速失去效价。我们的发现表明效价的优化需要仔细考虑培养条件，应针对载体生产细胞株进行个性化。