BACKGROUND & AIMS: We have isolated and characterized the first Xenopus transmembrane Eph ligand, XLerk (Xenopus Ligand for Eph Receptor Tyrosine Kinases). While this ligand has 72% identity with the closest mammalian family member, Lerk-2, it is the cytoplasmic domain of this molecule that is the most conserved domain with 95% identity. XLerk exists as a maternally expressed mRNA, however, expression of transcripts and protein increase during gastrulation and again in the late swimming tadpole stage. In the adult, XLerk is expressed at low levels in most adult tissues with increased levels observed in the kidney, oocytes, ovary and testis. While low levels of XLerk expression are observed in the adult brain, in situ hybridization analysis demonstrates prominent expression in the developing olfactory system, retina, hindbrain, cranial ganglia, and somites. Furthermore, we have shown that XLerk transcripts are significantly elevated during mesoderm induction caused by activin and FGF, but not during noggin-induced neuralization. These results suggest a role for XLerk in the developing mesenchymal and nervous tissue.

背景与目标： 我们已经分离并鉴定了第一个非洲爪蟾跨膜Eph配体XLerk（用于Eph受体酪氨酸激酶的非洲爪蟾配体）。尽管该配体与最接近的哺乳动物家族成员Lerk-2具有72％的同一性，但该分子的胞质结构域是具有95％的同一性的最保守的结构域。 XLerk作为母体表达的mRNA存在，但是转录的表达和蛋白质在胃排泄过程中以及游泳increase后期再次增加。在成年人中，XLerk在大多数成年人组织中低水平表达，在肾脏，卵母细胞，卵巢和睾丸中观察到水平升高。尽管在成年大脑中观察到了低水平的XLerk表达，但原位杂交分析显示出在发育中的嗅觉系统，视网膜，后脑，颅神经节和体节中突出表达。此外，我们已经表明，在由激活素和FGF引起的中胚层诱导过程中，XLerk转录物显着升高，但在头蛋白诱导的神经化过程中却没有。这些结果表明XLerk在发育中的间充质和神经组织中的作用。

BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

背景与目标： 最近的基因组搜索表明，许多基因位点与I型糖尿病易感性的推测联系。据报道，染色体2q31-35与I型糖尿病易感性相关，并被认为含有几个糖尿病易感性基因座。这些候选基因包括HOXD基因簇，BETA2，CTLA4，CD28，IGFBP2和IGFBP5。需要在人群和家庭中进行协会研究，以确认和/或识别实际的易感基因座。我们在此报告了HOXD8，BETA2和IGFBP5的几种先前未知的DNA多态性，并将其与HOXD8和CTLA4的先前已知多态性一起用于测试这些候选基因座是否为2q31-35染色体上的易感性基因。使用病例对照设计和随后的家庭关联方法来确认关联，我们没有发现这些候选基因与I型糖尿病易感性相关的证据。

BACKGROUND & AIMS: :There are numerous analytic and methodological limitations to current measures of drug market activity. This paper explores the structure of markets and individual user behavior to provide an integrated understanding of behavioral and economic (and market) aspects of illegal drug use with an aim toward developing improved procedures for measurement. This involves understanding the social processes that structure illegal distribution networks and drug users' interactions with them. These networks are where and how social behaviors, prices, and markets for illegal drugs intersect. Our focus is upon getting an up close measurement of these activities. Building better measures of consumption behaviors necessitates building better rapport with subjects than typically achieved with one-time surveys in order to overcome withholding and underreporting and to get a comprehensive understanding of the processes involved. This can be achieved through repeated interviews and observations of behaviors. This paper also describes analytic advances that could be adopted to direct this inquiry including behavioral templates, and insights into the economic valuation of labor inputs and cash expenditures for various illegal drugs. Additionally, the paper makes recommendations to funding organizations for developing the mechanisms that would support behavioral scientists to weigh specimens and to collect small samples for laboratory analysis-by providing protection from the potential for arrest. The primary focus is upon U.S. markets. The implications for other countries are discussed.

背景与目标： ：目前对药物市场活动的度量存在许多分析和方法学限制。本文探讨了市场结构和个人用户行为，以提供对非法药物使用的行为和经济（及市场）方面的综合理解，旨在开发改进的测量程序。这涉及了解构成非法分销网络和吸毒者与之互动的社会过程。这些网络是非法毒品的社会行为，价格和市场在何处以及如何相交的地方。我们的重点是仔细衡量这些活动。要建立更好的消费行为衡量标准，就必须与受试者建立更好的融洽关系，这要比一次调查更能实现，以克服扣缴和漏报的情况，并对所涉及的过程有一个全面的了解。这可以通过反复采访和观察行为来实现。本文还描述了可用于指导这一询问的分析进展，包括行为模板，以及对各种非法药物的劳动投入和现金支出的经济估值的见解。此外，该论文还向资助组织提出了建议，以开发机制，以支持行为科学家称量样本并收集小样本进行实验室分析，从而提供保护措施以防止被捕。主要重点是美国市场。讨论了对其他国家的影响。

BACKGROUND & AIMS: :Some alleles of the wtf gene family can increase their chances of spreading by using poisons to kill other alleles, and antidotes to save themselves.

背景与目标： ：wtf基因家族的某些等位基因可以通过使用毒药杀死其他等位基因和解毒剂来拯救自己，从而增加传播的机会。

BACKGROUND & AIMS: :Activating KIR-HLA-C ligand complexes and HLA-G∗14bp insertion/deletion (+/-) polymorphism were associated to Autism Spectrum Disorders (ASD) and were suggested to correlate with inflammation during fetal development. We evaluated whether HLA-G∗14bp(+/-) and KIR-HLA-C complexes are associated with cognitive and behavioral scores and EEG profile in 119 ASD children (58 from Sardinia, 61 from Peninsular Italy). KIR2DS1-C2; KIR2DS2-C1; KIR2DL1-C2; KIR2DL2-C1; KIR2DL3-C1 and HLA-G∗14bp(+/-) were molecularly genotyped by Single Specific Primer PCR and gel electrophoresis. Univariate linear model analysis adjusted for age, gender and provenience showed statistically higher scores of Childhood Autism Rating Scale (CARS) and Autistic Core Behavior in KIR2DS1-C2+/HLA-G∗14bp+ASD children (43.7±1.5, p=0.03; 3.3±0.1, p=0.03, respectively). These results suggested a synergistic polygenic association of KIR2DS1-HLAC2+/HLA-G∗14bp+ pattern with behavioral impairment in ASD children.

背景与目标： ：激活的KIR-HLA-C配体复合物和HLA-G * 14bp插入/缺失（/-）多态性与自闭症谱系障碍（ASD）相关，并被认为与胎儿发育过程中的炎症相关。我们评估了119名ASD儿童（58名来自撒丁岛，61名来自意大利半岛）的HLA-G * 14bp（/-）和KIR-HLA-C复合物是否与认知和行为评分以及脑电图谱相关。 KIR2DS1-C2; KIR2DS2-C1; KIR2DL1-C2; KIR2DL2-C1;通过单特异性引物PCR和凝胶电泳对KIR2DL3-C1和HLA-G * 14bp（/-）进行分子基因分型。根据年龄，性别和出身水平进行的单变量线性模型分析显示，在KIR2DS1-C2 / HLA-G * 14bp ASD儿童中，儿童自闭症评分量表（CARS）和自闭症核心行为的统计学得分较高（43.7±1.5，p = 0.03; 3.3±分别为0.1，p = 0.03）。这些结果表明，KIR2DS1-HLAC2 / HLA-G * 14bp模式与ASD儿童的行为障碍存在协同的多基因关联。

BACKGROUND & AIMS: BACKGROUND:The prevalence of lithiasis is increasing at all ages. This study aimed to assess the crystallization risk in urine from healthy school children and to determine urinary parameters that are most associated with it. METHODS:Urine samples were obtained from 184 children aged 5-12 years: a spot sample collected in the afternoon, and a 12-h overnight sample. Information was obtained regarding family histories of lithiasis. Urine volume, pH, and biochemical parameters of stone risk were measured. Crystallization risk was defined by the presence of specific urine conditions that had previously been associated with stone formation in vitro. RESULTS:Crystallization risk was observed in 15 % of spot urine samples and 54 % of 12-h samples. Metabolic abnormalities and a low urinary volume were more frequently detected in children with crystallization risk. Calcium excretion and calcium/citrate ratio were higher in children with a family history of lithiasis. CONCLUSIONS:We observed a high prevalence of crystallization risk in urine, especially in children with a family history of the disease. Low urinary volume was the factor most associated with increased risk. Adequate fluid intake at an early age may be a simple and effective measure to reduce the incidence of nephrolithiasis.

背景与目标： 背景：石斑症的患病率在各个年龄段都在增加。这项研究旨在评估健康学童尿液中结晶的风险，并确定与其最相关的尿液参数。
方法：从184名5-12岁的儿童中获取尿液样本：下午收集现场样本，并收集12小时的过夜样本。获得了有关石尿症家族史的信息。测量尿液体积，pH值和结石风险的生化参数。结晶风险是由以前与体外结石形成有关的特定尿液条件定义的。
结果：在15％的现货尿液样本和54％的12小时样本中观察到结晶风险。具有结晶风险的儿童更经常检测到代谢异常和尿量低。有结石病家族史的儿童的钙排泄和钙/柠檬酸比更高。
结论：我们观察到尿液中结晶风险的患病率很高，尤其是在有该病家族史的儿童中。低尿量是与增加风险最相关的因素。早期摄入足够的液体可能是减少肾结石症发生率的一种简单有效的措施。

BACKGROUND & AIMS: BACKGROUND:Abnormal respiratory rates are one of the first indicators of clinical deterioration in emergency department(ED) patients. Despite the importance of respiratory rate observations, this vital sign is often inaccurately recorded on ED observation charts, compromising patient safety. Concurrently, there is a paucity of research reporting why this phenomenon occurs. OBJECTIVE:To develop a substantive theory explaining ED registered nurses' reasoning when they miss or misreport respiratory rate observations. DESIGN:This research project employed a classic grounded theory analysis of qualitative data. PARTICIPANTS:Seventy-nine registered nurses currently working in EDs within Australia. Data collected included detailed responses from individual interviews and open-ended responses from an online questionnaire. METHODS:Classic grounded theory (CGT) research methods were utilised, therefore coding was central to the abstraction of data and its reintegration as theory. Constant comparison synonymous with CGT methods were employed to code data. This approach facilitated the identification of the main concern of the participants and aided in the generation of theory explaining how the participants processed this issue. RESULTS:The main concern identified is that ED registered nurses do not believe that collecting an accurate respiratory rate for ALL patients at EVERY round of observations is a requirement, and yet organizational requirements often dictate that a value for the respiratory rate be included each time vital signs are collected. The theory 'Rationalising Transgression', explains how participants continually resolve this problem. The study found that despite feeling professionally conflicted, nurses often erroneously record respiratory rate observations, and then rationalise this behaviour by employing strategies that adjust the significance of the organisational requirement. These strategies include; Compensating, when nurses believe they are compensating for errant behaviour by enhancing the patient's outcome; Minimalizing, when nurses believe that the patient's outcome would be no different if they recorded an accurate respiratory rate or not and; Trivialising, a strategy that sanctions negligent behaviour and occurs when nurses 'cut corners' to get the job done. Nurses' use these strategies to titrate the level ofemotional discomfort associated with erroneous behaviour, thereby rationalising transgression CONCLUSION: This research reveals that despite continuing education regarding gold standard guidelines for respiratory rate collection, suboptimal practice continues. Ideally, to combat this transgression, a culture shift must occur regarding nurses' understanding of acceptable practice methods. Nurses must receive education in a way that permeates their understanding of the relationship between the regular collection of accurate respiratory rate observations and optimal patient outcomes.

背景与目标： 背景：呼吸频率异常是急诊科（ED）患者临床恶化的首批指标之一。尽管进行呼吸频率观察很重要，但这种生命体征常常不准确地记录在ED观察图上，从而损害了患者的安全性。同时，很少有研究报告这种现象发生的原因。
目的：建立一个实质性的理论来解释急诊室注册护士错过或误报呼吸频率观察值时的推理。
设计：该研究项目对定性数据进行了经典的扎根理论分析。
参与者：目前在澳大利亚的急诊室工作的九十九名注册护士。收集的数据包括个人访谈的详细答复和在线调查表的开放式答复。
方法：由于采用了经典的扎根理论（CGT）研究方法，因此编码对于数据的抽象及其作为理论的重新整合至关重要。与CGT方法同义的常量比较用于编码数据。这种方法有助于确定参与者的主要关注点，并有助于产生解释参与者如何处理此问题的理论。
结果：确定的主要问题是，急诊科注册护士并不认为需要在每一轮观察中为所有患者收集准确的呼吸频率，但是组织要求经常要求每次重要时都应包括呼吸频率值收集迹象。 “合理化违法行为”理论解释了参与者如何持续解决这一问题。研究发现，尽管感到职业上有矛盾，但护士经常会错误地记录呼吸频率的观察结果，然后通过采用可调整组织要求重要性的策略来合理化这种行为。这些策略包括：补偿：当护士认为他们通过提高患者的治疗效果来补偿错误的行为时；当护士认为患者记录正确的呼吸频率与否时，结局没有什么不同，并且最小化；琐事化是一种惩罚过失行为的策略，当护士“偷工减料”完成工作时就会发生。护士使用这些策略来减轻与错误行为有关的情绪不适水平，从而使过犯合理化。结论：本研究表明，尽管继续接受有关呼吸频率收集的金标准指南的教育，但最佳实践仍在继续。理想情况下，为了应对这种违法行为，必须在护士对可接受的练习方法的理解上发生文化转变。护士必须接受一定程度的教育，以使他们了解定期收集的准确呼吸频率观察值与患者最佳结局之间的关系。

BACKGROUND & AIMS: :A Gram-negative, rod shaped, motile bacterium, was isolated from a marine solar saltern sample collected from Kakinada, India. Strain AK2(T) was determined to be positive for nitrate reduction, catalase, Ala-Phe-Pro-arylamidase, β-galactosidase, β-N-acetylglucosaminidase, β-glucosidase, β-xylosidase, α-glucosidase, α-galactosidase and phosphatase activities, hydrolysis of aesculin, Tween 20/40/60/80 and urea. It was determined to be negative for oxidase, lysine decarboxylase and ornithine decarboxylase activities and could not hydrolyze agar, casein, gelatin and starch. The predominant fatty acids were identified as iso-C(15:0) (28.2 %), anteiso-C(15:0) (23.2 %), iso-C(13:0) (19.9 %) and iso-C(15:0) 3-OH (13.9 %). Strain AK2(T) was found to contain menaquinone with seven isoprene units (MK-7) as the sole respiratory quinone and phosphatidylethanolamine, one unidentified phospholipid and three unidentified lipids as polar lipids. The 16S rRNA gene sequence analysis indicated the strain AK2(T) as a member of the genus Marinilabilia and is closely related to Marinilabilia salmonicolor with pair-wise sequence similarity of 98.2 %. Phylogenetic analysis of 16S rRNA gene revealed that the strain AK2(T) clustered with M. salmonicolor. However, DNA-DNA hybridization with M. salmonicolor JCM 21150(T) showed a relatedness of 48 ± 0.5 % with respect to strain AK2(T). The DNA G+C content of the strain was determined to be 40.2 mol%. Based on the phenotypic characteristics and phylogenetic inference, it is proposed that the strain AK2(T) represents a novel species of the genus Marinilabilia, for which the name Marinilabilia nitratireducens sp. nov. is proposed. The type strain of M. nitratireducens sp. nov. is AK2(T) (= MTCC 11402(T) = JCM 17679(T)).

背景与目标： ：从印度Kakinada收集的海洋太阳能盐分离器样本中分离出革兰氏阴性，棒状，能动细菌。确定菌株AK2（T）对硝酸盐还原，过氧化氢酶，Ala-Phe-前芳酰胺酶，β-半乳糖苷酶，β-N-乙酰氨基葡糖苷酶，β-葡萄糖苷酶，β-木糖苷酶，α-葡萄糖苷酶，α-半乳糖苷酶和磷酸酶活性，七叶皂苷，Tween 20/40/60/80和尿素的水解。它被确定为氧化酶，赖氨酸脱羧酶和鸟氨酸脱羧酶活性阴性，并且不能水解琼脂，酪蛋白，明胶和淀粉。主要脂肪酸被鉴定为iso-C（15：0）（28.2％），anteiso-C（15：0）（23.2％），iso-C（13：0）（19.9％）和iso-C（ 15：0）3-OH（13.9％）。发现菌株AK2（T）含有具有七个异戊二烯单元（MK-7）的甲基萘醌作为唯一的呼吸醌和磷脂酰乙醇胺，一个未确定的磷脂和三个未确定的脂质作为极性脂质。 16S rRNA基因序列分析表明，菌株AK2（T）是马里尼布拉马氏菌属的成员，与马里尼拉鲑鱼色密切相关，成对序列相似性为98.2％。 16S rRNA基因的系统发育分析表明，菌株AK2（T）与沙门氏菌成簇。但是，与鲑鱼支原体JCM 21150（T）的DNA-DNA杂交显示出与菌株AK2（T）的相关性为48±0.5％。测得该菌株的DNA G C含量为40.2mol％。根据表型特征和系统发育推论，建议菌株AK2（T）代表Marinilabilia属的一个新种，其名称为Marinilabilianitroatireducens sp。十一月被提议。硝化分枝杆菌的类型菌株。十一月是AK2（T）（= MTCC 11402（T）= JCM 17679（T））。

BACKGROUND & AIMS: :The purpose of this investigation was to evaluate the effectiveness of a behavioral treatment package to reduce chronic sleep problems in children with Angelman Syndrome. Participants were five children, 2-11 years-of-age. Parents maintained sleep diaries to record sleep and disruptive nighttime behaviors. Actigraphy was added to provide independent evaluations of sleep-wake activity. The treatment package targeted the sleep environment, the sleep-wake schedule, and parent-child interactions during sleep times. Treatment was introduced sequentially, across families, and evaluated in an interrupted time series, multiple baseline design. Data show that prior to treatment, baseline rates of nighttime disruptive behavior were stable or increasing and none of the participants were falling to sleep independently. With the introduction of treatment, all participants quickly learned to initiate sleep independently. Gradual reductions were reported in disruptive behaviors and these improvements were sustained over time. Results were replicated with two participants when treatment was withdrawn and reinstated. Changes in disruptive bedtime behaviors and in sleep onset were found to be statistically significant. Parents indicated high satisfaction with the treatment. A behavioral treatment package was found to be effective with five children with long histories of significant sleep-related behavior problems. These results suggest that behavioral treatment may be a reasonable way to address sleep problems in some children with Angelman Syndrome.

背景与目标： ：这项研究的目的是评估行为治疗方案以减少Angelman综合征患儿的慢性睡眠问题的有效性。参加者为5个年龄在2-11岁之间的儿童。父母保留睡眠日记以记录睡眠和夜间行为。增加了书法，以提供对睡眠觉醒活动的独立评估。该治疗方案针对睡眠环境，睡眠唤醒计划以及睡眠期间的亲子互动。在各个家庭中按顺序引入治疗方法，并在中断的时间序列和多个基线设计中进行评估。数据显示，在治疗之前，夜间破坏行为的基线率稳定或上升，并且没有参与者独立入睡。随着治疗的引入，所有参与者很快学会了独立开始睡眠。据报道，破坏性行为逐渐减少，并且随着时间的推移，这些改善持续存在。撤回治疗并恢复治疗时，两名参与者重复了结果。发现破坏性的就寝时间行为和睡眠发作的变化在统计学上是显着的。父母对治疗表示高度满意。发现行为治疗一揽子方法对五个有悠久的重大睡眠相关行为问题病史的儿童有效。这些结果表明，行为治疗可能是解决某些Angelman综合征儿童睡眠问题的合理方法。

BACKGROUND & AIMS: :A specific form of family therapy (family-based treatment) is the leading treatment for adolescents with anorexia nervosa. As this treatment has certain limitations, alternative approaches are needed. "Enhanced" cognitive behaviour therapy (CBT-E) is a potential candidate given its utility as a treatment for adults with eating disorder psychopathology. The aim of the present study was to establish, in a representative cohort of patients with marked anorexia nervosa, the immediate and longer term outcome following CBT-E. Forty-nine adolescent patients were recruited from consecutive referrals to a community-based eating disorder clinic. Each was offered 40 sessions of CBT-E over 40 weeks from a single therapist. Two-thirds completed the full treatment with no additional input. In these patients there was a substantial increase in weight together with a marked decrease in eating disorder psychopathology. Over the 60-week post-treatment follow-up period there was little change despite minimal subsequent treatment. These findings suggest that CBT-E may prove to be a cost-effective alternative to family-based treatment.

背景与目标： ：一种特殊形式的家庭治疗（基于家庭的治疗）是神经性厌食症青少年的主要治疗方法。由于这种治疗有一定的局限性，因此需要其他方法。鉴于“增强型”认知行为疗法（CBT-E）可用于患有饮食失调症的心理病理学成年人，因此是一种潜在的候选药物。本研究的目的是在具有明显神经性厌食症的患者的代表性队列中建立CBT-E术后的近期和长期预后。从连续转诊到社区饮食失调诊所招募了49名青少年患者。一位治疗师在40周内为每位患者提供了40次CBT-E疗程。三分之二的人完成了全部治疗，没有其他投入。在这些患者中，体重显着增加，而进食障碍的精神病理学显着下降。在治疗后的60周随访期内，尽管后续治疗最少，但变化不大。这些发现表明，CBT-E可能被证明是替代基于家庭的治疗的一种经济有效的选择。

BACKGROUND & AIMS: :Development of new endocrine disruption-relevant test methods has been the subject of intensive research efforts for the past several decades, prompted in part by mandates in the 1996 Food Quality Protection Act (FQPA). While scientific understanding and test methods have advanced, questions remain on whether current scientific methods are capable of adequately addressing the complexities of the endocrine system for regulatory health and ecological risk assessments. The specific objective of this article is to perform a comprehensive, detailed evaluation of the adequacy of current test methods to inform regulatory risk assessments of whether a substance has the potential to perturb endocrine-related pathways resulting in human adverse effects. To that end,  approximately 42 existing test guidelines (TGs) were considered in the evaluation of coverage for endocrine-related adverse effects. In addition to evaluations of whether test methods are adequate to capture endocrine-related effects, considerations of further enhancements to current test methods, along with the need to develop novel test methods to address existing test method gaps are described. From this specific evaluation, up to 35 test methods are capable of informing whether a chemical substance perturbs known endocrine related biological pathways. Based on these findings, it can be concluded that current validated test methods are adequate to discern substances that may perturb the endocrine system, resulting in an adverse health effect. Together, these test methods predominantly form the core data requirements of a typical food-use pesticide registration submission. It is recognized, however, that the current state of science is rapidly advancing and there is a need to update current test methods to include added enhancements to ensure continued coverage and public health and environmental protection.

背景与目标： 在过去的几十年中，新的内分泌干扰物相关测试方法的开发一直是深入研究的主题，这在一定程度上是由1996年《食品质量保护法》（FQPA）的授权推动的。尽管科学的理解和测试方法已经取得了进步，但目前的科学方法是否能够充分解决内分泌系统的复杂性，以进行监管健康和生态风险评估仍存在疑问。本文的具体目标是对当前测试方法的适当性进行全面，详细的评估，以为某种物质是否具有干扰内分泌相关途径而导致人为不良影响的潜在风险提供监管风险评估。为此，在评估内分泌相关不良反应的覆盖范围时，考虑了大约42种现有的测试指南（TG）。除了评估测试方法是否足以捕获与内分泌相关的作用外，还描述了对当前测试方法进一步增强的考虑，以及开发新型测试方法以解决现有测试方法空白的需求。通过这种特定的评估，多达35种测试方法能够告知化学物质是否干扰了与内分泌有关的生物学途径。基于这些发现，可以得出结论，当前经过验证的测试方法足以识别可能扰乱内分泌系统，对健康产生不利影响的物质。这些测试方法共同构成了典型的食品用农药注册提交文件的核心数据要求。但是，已经认识到，当前的科学状态正在迅速发展，需要更新当前的测试方法以包括更多的增强功能，以确保持续的覆盖范围以及公共卫生和环境保护。

BACKGROUND & AIMS: :Proteins encoded by MADS-box genes are important transcription factors involved in the regulation of flowering plant growth and development. Currently, no systematic information exists regarding the MADS-box family in the important tropical fruit banana. Ninety-six MADS-box genes were identified from the banana (Pahang) A genome. Phylogenetic analysis indicated that Musa acuminata MCM1-AGAMOUS- DEFICIENS-SRF (MaMADS) could be divided into MIKCc, MIKC*, Mα/β and Mγ groups. MIKCc could be further divided into 11 subfamilies, which was further supported by conserved motif and gene structure analyses. Transcriptome analysis on the Feng Jiao (FJ) and BaXi Jiao (BX) banana cultivars revealed that MaMADS genes are differentially expressed in various organs, at different fruit development and ripening stages, indicating the involvement of these genes in fruit development and ripening processes. Interactive network analysis indicated that MaMADS24 and 49 not only interacted with MaMADS proteins themselves, but also interacted with hormone-response proteins, ethylene signal transduction and biosynthesis-related proteins, starch biosynthesis proteins and metabolism-related proteins. This systematic analysis identified candidate MaMADS genes related to fruit development and ripening for further functional characterization in plants, and also provided new insights into the transcriptional regulation of MaMADS genes, facilitating the future genetic manipulation of MADS-mediated fruit development and ripening.

背景与目标： MADS-box基因编码的蛋白质是重要的转录因子，参与开花植物生长发育的调控。目前，在重要的热带水果香蕉中，尚无有关MADS盒家族的系统信息。从香蕉（彭亨州）A基因组中鉴定出96个MADS-box基因。系统发育分析表明，Musus acuminata MCM1-AGAMOUS-DEFICIENS-SRF（MaMADS）可以分为MIKCc，MIKC *，Mα/β和Mγ组。 MIKCc可以进一步分为11个亚家族，这由保守的基序和基因结构分析进一步支持。凤角（FJ）和八喜角（BX）香蕉品种的转录组分析表明，MaMADS基因在不同器官中处于不同的果实发育和成熟阶段差异表达，表明这些基因参与了果实发育和成熟过程。交互网络分析表明，MaMADS24和49不仅与MaMADS蛋白本身相互作用，而且还与激素响应蛋白，乙烯信号转导和生物合成相关蛋白，淀粉生物合成蛋白和代谢相关蛋白相互作用。这项系统分析确定了与果实发育和成熟有关的候选MaMADS基因，以进一步在植物中进行功能表征，也为MaMADS基因的转录调控提供了新见识，从而促进了MADS介导的果实发育和成熟的未来遗传调控。

BACKGROUND & AIMS: :Little is known about molecular recognition of acetylated N termini, despite prevalence of this modification among eukaryotic cytosolic proteins. We report that the family of human DCN-like (DCNL) co-E3s, which promote ligation of the ubiquitin-like protein NEDD8 to cullin targets, recognizes acetylated N termini of the E2 enzymes UBC12 and UBE2F. Systematic biochemical and biophysical analyses reveal 40- and 10-fold variations in affinities among different DCNL-cullin and DCNL-E2 complexes, contributing to varying efficiencies of different NEDD8 ligation cascades. Structures of DCNL2 and DCNL3 complexes with N-terminally acetylated peptides from UBC12 and UBE2F illuminate a common mechanism by which DCNL proteins recognize N-terminally acetylated E2s and how selectivity for interactions dependent on N-acetyl-methionine are established through side chains recognizing distal residues. Distinct preferences of UBC12 and UBE2F peptides for inhibiting different DCNLs, including the oncogenic DCNL1 protein, suggest it may be possible to develop small molecules blocking specific N-acetyl-methionine-dependent protein interactions.

背景与目标： ：尽管在真核细胞溶质蛋白中普遍存在这种修饰，但对乙酰化N末端的分子识别知之甚少。我们报告说，人类DCN样（DCNL）co-E3s的家族，促进泛素样蛋白NEDD8与cullin目标的连接，识别E2酶UBC12和UBE2F的乙酰化N末端。系统的生化和生物物理分析表明，不同DCNL-cullin和DCNL-E2复合物之间的亲和力变化为40倍和10倍，从而导致不同NEDD8连接级联反应的效率不同。具有来自UBC12和UBE2F的N末端乙酰化肽的DCNL2和DCNL3配合物的结构阐明了DCNL蛋白质识别N末端乙酰化E2的共同机制以及如何通过识别远端残基的侧链建立依赖N-乙酰甲硫氨酸的相互作用的选择性。 UBC12和UBE2F肽对抑制不同的DCNL（包括致癌DCNL1蛋白）的偏好不同，这表明可能开发出阻断特定N-乙酰基-蛋氨酸依赖性蛋白相互作用的小分子。

BACKGROUND & AIMS: BACKGROUND:There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. METHODS:In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. RESULTS:We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. CONCLUSIONS:We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally, a simulation should be based on real data for adequately reflecting complex observational data structures, such as found in epidemiological cohort studies.

背景与目标： 背景技术：越来越多的观察性研究不仅关注单个生物标志物来预测结果事件，而且在多变量环境中解决问题。例如，当量化除已建立的风险因素外的新生物标记物的附加值时，目标可能是就其预测性能对几种新标记物进行排名。因此，重要的是要考虑标记物相关结构以进行此类研究。由于其复杂性，可能需要一种仿真方法来充分评估样本大小或其他方面，例如性能指标的选择。
方法：在基于真实数据的模拟研究中，我们调查了如何生成具有实际分布的协变量以及应使用哪种生成模型进行结果计算，目的是确定获得实际结果所需的最少信息量和复杂度。大型流行病学队列研究作为模拟的基础，使用了古腾堡健康研究。对标记的增加值进行量化，并在该总体数据的子采样数据集中进行排名，并根据排名的质量来判断模拟方法。评估方法之一是随机森林，它需要各个级别的原始数据。因此，还研究了基于随机森林的模拟试验研究规模的影响。
结果：我们发现简单的逻辑回归模型无法充分生成现实数据，即使具有交互项或非线性效应等扩展。人们认为，随机森林方法更适合于复杂数据结构的仿真。从大约250个观察值开始的试点研究被认为为该方法提供了合理水平的信息。
结论：我们建议避免过度简化的回归模型进行仿真，尤其是在关注多变量研究问题时。更一般而言，模拟应基于真实数据，以充分反映复杂的观察数据结构，例如流行病学队列研究中发现的结构。

BACKGROUND & AIMS: OBJECTIVE:Replacement of standard immunofluorescence methods with bead-based assays for antinuclear antibody (ANA) testing is a new clinical option. The aim of this study was to evaluate a large, multiethnic cohort of patients with systemic lupus erythematosus (SLE), blood relatives, and unaffected control individuals for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods. METHODS:Serum samples (1,540 SLE patients, 1,154 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, indirect immunofluorescence (IIF), and immunodiffusion. Autoantibody prevalence, sensitivity for disease detection, clustering of autoantibodies, and associations between newer methods and standard immunodiffusion results were evaluated. RESULTS:The frequencies of ANAs in the sera from African American, Hispanic, and European American patients with SLE were 89%, 73%, and 67%, respectively, by BioPlex 2200 bead-based assay and 94%, 84%, and 86%, respectively, by IIF. When comparing the serum prevalence of 60-kd Ro, La, Sm, nuclear RNP A, and ribosomal P autoantibodies across assays, the sensitivity of detection ranged from 0.92 to 0.83 and the specificity ranged from 0.90 to 0.79. Autoantibody cluster analysis showed associations of autoantibody specificities in 3 subsets: 1) 60 kd Ro, 52-kd Ro, and La, 2) spliceosomal proteins, and 3) double-stranded DNA (dsDNA), chromatin, and ribosomal P. Familial aggregation of Sm/RNP, ribosomal P, and 60-kd Ro in SLE patient sibling pairs was observed (P ≤ 0.004). Simplex-pedigree SLE patients had a greater prevalence of dsDNA (P = 0.0003) and chromatin (P = 0.005) autoantibodies compared to patients with a multiplex SLE pedigree. CONCLUSION:The frequencies of ANAs detected by a bead-based assay are lower than those detected by IIF in European American patients with SLE. These assays have strong positive predictive values across ethnic groups, provide useful information for clinical care, and provide unique insights into familial aggregation and autoantibody clustering.

背景与目标： 目的：用基于微珠的抗核抗体（ANA）检测方法代替标准的免疫荧光方法是一种新的临床选择。这项研究的目的是通过高通量血清筛查技术和传统方法评估系统性红斑狼疮（SLE）患者，血亲和未受影响对照个体的大型，多种族队列，以进行家族聚集和自身抗体的子集聚。
方法：使用基于珠的检测，间接免疫荧光（IIF）和免疫扩散分析血清样本（1,540名SLE患者，1,154名未受影响的亲戚和906名健康的，基于人群的对照）的SLE自身抗体。自身抗体的流行率，疾病检测的敏感性，自身抗体的聚类，以及新方法和标准免疫扩散结果之间的关联进行了评估。
结果：通过BioPlex 2200珠基检测法，非裔，西班牙裔和欧洲裔SLE患者血清中的ANA频率分别为89％，73％和67％，分别为94％，84％和86 IIF分别为％。在整个试验中比较血清中60 kd Ro，La，Sm，核RNP A和核糖体P自身抗体的患病率时，检测的灵敏度为0.92至0.83，特异性为0.90至0.79。自身抗体簇分析显示了3个子集中的自身抗体特异性的关联：1）60 kd Ro，52 kd Ro和La，2）剪接体蛋白和3）双链DNA（dsDNA），染色质和核糖体P.家族聚集观察到SLE患者同胞对中Sm / RNP，核糖体P和60 kd Ro的变化（P≤0.004）。与具有多重SLE谱系的患者相比，单纯谱系SLE患者的dsDNA（P = 0.0003）和染色质（P = 0.005）自身抗体的患病率更高。
结论：在美国SLE患者中，基于微珠的检测方法检测到的ANAs频率低于IIF检测的频率。这些测定法在各个族裔中都具有很强的阳性预测价值，可为临床护理提供有用的信息，并提供有关家族聚集和自身抗体聚类的独特见解。