Accurate prediction of disorder in protein chains with a comprehensive and empirically designed consensus

Availability of computational methods that predict disorder from protein sequences fuels rapid advancements in the protein disorder field. The most accurate predictions are usually obtained with consensus-based approaches. However, their design is performed in an ad hoc manner. We perform first-of-its-kind rational design where we empirically search for an optimal mixture of base methods, selected out of a comprehensive set of 20 modern predictors, and we explore several novel ways to build the consensus. Our method for the prediction of disorder based on Consensus of Predictors (disCoP) combines seven base methods, utilizes custom-designed set of selected 11 features that aggregate base predictions over a sequence window and uses binomial deviance loss-based regression to implement the consensus. Empirical tests performed on an independent benchmark set (with low-sequence similarity compared with proteins used to design disCoP), shows that disCoP provides statistically significant improvements with at least moderate magnitude of differences. disCoP outperforms 28 predictors, including other state-of-the-art consensuses, and achieves Area Under the ROC Curve of .85 and Matthews Correlation Coefficient of .5 compared with .83 and .48 of the best considered approach, respectively. Our consensus provides high rate of correct disorder predictions, especially when low rate of incorrect disorder predictions is desired. We are first to comprehensively assess predictions in the context of several functional types of disorder and we demonstrate that disCoP generates accurate predictions of disorder located at the post-translational modification sites (in particular phosphorylation sites) and in autoregulatory and flexible linker regions. disCoP is available at http://biomine.ece.ualberta.ca/disCoP/.     

Circadian Uses of Melatonin in Humans

Melatonin in humans can be an independent or dependent variable. Measurement of endogenous melatonin levels under dim‐light conditions, particularly the dim‐light melatonin onset (DLMO), has received increasing attention among researchers, and for clinicians it may soon become a convenient test that can be done at home using saliva collections in the evening, without interfering with sleep. Melatonin, even at low physiological doses, can cause advances (shifts to an earlier time) or delays (shifts to a later time) depending on when it is administered on its phase‐response curve (in most sighted people, these times are approximately in the p.m. and in the a.m., respectively). Although both bright light and melatonin can be used separately or together in the treatment of circadian phase disorders in sighted people—such as advanced and delayed sleep phase syndromes, jet lag, shift‐work maladaptation, and winter depression (seasonal affective disorder, or SAD)—melatonin is the treatment of choice in totally blind people. These people provide a unique opportunity to study the human circadian system without the overwhelming effects of ocularly mediated light, thus permitting us to establish that all blind free‐runners (BFRs) studied under high resolution appear to have phase‐advancing and phase‐delaying responses to as yet unidentified zeitgebers (time givers) that are usually too weak to result in entrainment.     

Disturbed Sleep in Shift Workers,Day Workers,and Insomniacs

Very little is known about differences in sleep between day and shift workers in representative samples of the population. This study compared a national representative sample (N=3400) of shift (with night shifts) and day workers regarding the different types of sleep disturbances and also the level of sleep symptoms with that of insomnia patients. The results showed very few differences between shift and day workers; only “too little sleep” and “nodding off at work” were marginally higher among shift workers. The results also showed that the complaints of insomnia patients for most sleep disturbances corresponded to the 2nd–16th percentile of the shift workers' levels of complaints. The results suggest, at least with the present questionnaire methodology, that shift work does not appear to be a major source of sleep disturbances and that their complaint levels bear no resemblance to those seen in insomniac patients.     

On the functional and structural characterization of hubs in protein–protein interaction networks

A number of interesting issues have been addressed on biological networks about their global and local properties. The connection between the topological properties of proteins in Protein–Protein Interaction (PPI) networks and their biological relevance has been investigated focusing on hubs, i.e. proteins with a large number of interacting partners. We will survey the literature trying to answer the following questions: Do hub proteins have special biological properties? Do they tend to be more essential than non-hub proteins? Are they more evolutionarily conserved? Do they play a central role in modular organization of the protein interaction network? Are there structural properties that characterize hub proteins?     

A potential link among biogenic amines-based pesticides,learning and memory,and colony collapse disorder: A unique hypothesis

Pesticides are substances that have been widely used throughout the world to kill, repel, or control organisms such as certain forms of plants or animals considered as pests. Depending on their type, dose, and persistence in the environment, they can have impact even on non-target species such as beneficial insects (honeybees) in different ways, including reduction in their survival rate and interference with their reproduction process. Honeybee Apis mellifera is a major pollinator and has substantial economical and ecological values. Colony collapse disorder (CCD) is a mysterious phenomenon in which adult honeybee workers suddenly abandon from their hives, leaving behind food, brood, and queen. It is lately drawing a lot of attention due to pollination crisis as well as global agriculture and medical demands. If the problem of CCD is not resolved soon enough, this could have a major impact on food industry affecting world’s economy a big time. Causes of CCD are not known. In this overview, I discuss CCD, biogenic amines-based-pesticides (neonicotinoids and formamidines), and their disruptive effects on biogenic amine signaling causing olfactory dysfunction in honeybees. According to my hypothesis, chronic exposure of biogenic amines-based-pesticides to honeybee foragers in hives and agricultural fields can disrupt neural cholinergic and octopaminergic signaling. Abnormality in biogenic amines-mediated neuronal signaling impairs their olfactory learning and memory, therefore foragers do not return to their hive – a possible cause of CCD. This overview is an attempt to discuss a hypothetical link among biogenic amines-based pesticides, olfactory learning and memory, and CCD.     

妊娠高血压疾病对妊娠结局的影响及防治对策探讨

目的：研究妊娠高血压疾病对妊娠结局的影响及防治对策讨论。方法：选择回顾性研究方法,选择2010年9月到2012年8月到我院的妊娠高血压患者60名作为观察组,并且同期选择60名正常妊娠妇女作为对照组,比较妊娠高血压患者的母体并发症（早产、胎盘早剥、产后出血）等及胎儿妊娠结局等情况与对照组的比较。结果：妊娠高血压患者不同程度对妊娠结局的影响不同P〈0．05,并且妊娠高血压患者的母体并发症与对新生儿的影响与对照组比较有差异P〈0．05,异常情况均较正常妊娠妇女要高。结论：妊娠高血压患者对妊娠结局的影响较为严重,对母婴危害严重,需积极预防。     

Cyclin B1和p21在妊娠期高血压产妇胎盘组织中的表达及其临床意义

目的:观察CyclinB1和p21在妊娠期高血压产妇胎盘组织中的表达并探讨其临床意义.方法:采用免疫组化MaxVision法检测正常胎盘组织(20例)、妊娠期高血压胎盘组织(30例)、轻度子痫前期胎盘组织(30例)和重度子痫前期(30例)产妇胎盘组织中的cyclin B1和p21蛋白表达,并分析其与妊娠期高血压病情严重程度的相关性.结果:妊娠期高血压、轻度子痈前期、重度子痈前期胎盘组织中cyclinB1蛋白的表达均显著低于正常胎盘组织,差异均有统计学意义(P＜0.05),妊娠期高血压、轻度子痈前期、重度子痈前期胎盘组织中p21蛋白表达均显著高于正常胎盘组织,差异有统计学意义(P＜0.05).妊娠期高血压患者病情的严重程度与其胎盘组织中cyclinB1的蛋白表达呈显著负相关(r=0.641,P=0.000);而与其胎盘组织中p21蛋白的表达呈显著正相关(r=0.635,P=0.000).结论:Cyclin B1蛋白的表达下调和p21蛋白的表达上调可能参与了妊娠期高血压的发生发展,且二者在胎盘组织中的表达水平与妊娠期高血压病情的严重程度显著相关.     

脑外伤所致精神障碍的危险因素分析

目的：探究脑外伤所致精神障碍的的危险因素,以探究各类因素与脑外伤患者预后的关联,为今后的临床治疗及干预措施提供理论依据。方法：对我院2009年6月-2012年9月收治的217例脑外伤患者进行回顾分析,按照其是否出现精神障碍分为精神障碍组及非精神障碍组,对比其临床资料,将存在统计学意义的指标纳入Logistic多因素回归分析,探讨脑外伤所致精神障碍的的危险因素。结果：217例脑外伤患者共出现162例精神障碍,精神障碍发病率74．7％;两组患者一般资料对比可见,颅内血肿、脑干损伤、脑叶损伤范围、GCS评分及EPQ评分存在统计学意义（p〈0．05）;多因素回归分析发现,GCS评分s8分及EPQ评分≥30分存在统计学差异（p〈0．05）,是影响脑外伤所致精神障碍的独立危险因素。结论：GCS评分s8分及EPQ评分≥30分存在统计学差异（p〈0．05）,是影响脑外伤所致精神障碍的独立危险因素,应在患者接受常规脑外伤治疗后进行环境护理、日常生活护理及心理护理,改善其不稳定情绪,并对其意识状态进行密切监测,必要时可预防性使用抗精神病药物,以降低患者精神障碍患病率,改善其生活质量。     

Measures to improve dairy cow foot health: consequences for farmer income and dairy cow welfare

Dairy farming in western countries with cubicle housing is an efficient way of dairy farming. Though, a disadvantage is the high prevalence and incidence of foot disorders (clinical and subclinical), which cause high economic losses and also seriously impair the welfare of dairy cattle. To point out the importance of reducing the amount and severity of foot disorders, advice to farmers should include information about the scale of the problem and the consequences in terms of economics and animal welfare. To provide support in making decisions on implementing intervention measures, insight into costs and benefits of different measures should be available. The objective of this study, therefore, is to provide more insight into the costs and benefits, for farmer and cow, of different intervention measures to improve dairy cow foot health. Intervention measures were modeled when they were applicable on a dairy farm with cubicle housing and when sufficient information was available in literature. Net costs were calculated as the difference between the costs of the measure and the economic benefits resulting from the measure. Welfare benefits were calculated as well. Cost-effective measures are: improving lying surface (mattress and bedding, €7 and €1/cow per year, respectively), reducing stocking density (break even) and performing additional foot trimming (€1/cow per year). Simultaneously, these measures have a relative high welfare benefit. Labor costs play an important role in the cost-effectiveness of labor-intensive measures. More insight into cost-effectiveness and welfare benefits of intervention measures can help to prioritize when choosing between intervention measures.