Development of a sequence based method for the prediction of protein function

Imperial Users onl

Parsing eye-tracking data of variable quality to provide accurate fixation duration estimates in infants and adults

Researchers studying infants’ spontaneous allocation of attention have traditionally relied on hand-coding infants’ direction of gaze from videos; these techniques have low temporal and spatial resolution and are labor intensive. Eye-tracking technology potentially allows for much more precise measurement of how attention is allocated at the subsecond scale, but a number of technical and methodological issues have given rise to caution about the quality and reliability of high temporal resolution data obtained from infants. We present analyses suggesting that when standard dispersal-based fixation detection algorithms are used to parse eye-tracking data obtained from infants, the results appear to be heavily influenced by interindividual variations in data quality. We discuss the causes of these artifacts, including fragmentary fixations arising from flickery or unreliable contact with the eyetracker and variable degrees of imprecision in reported position of gaze. We also present new algorithms designed to cope with these problems by including a number of new post hoc verification checks to identify and eliminate fixations that may be artifactual. We assess the results of our algorithms by testing their reliability using a variety of methods and on several data sets. We contend that, with appropriate data analysis methods, fixation duration can be a reliable and stable measure in infants. We conclude by discussing ways in which studying fixation durations during unconstrained orienting may offer insights into the relationship between attention and learning in naturalistic settings

Metabolic syndrome in polycystic ovary syndrome

Zespół metaboliczny (MS, metabolic syndrome) i zespół policystycznych jajników (PCOS, polycystic ovary syndrome) są często rozpoznawanymi zaburzeniami u kobiet. Częstość występowania zespołu metabolicznego u kobiet z PCOS zależy od zastosowanych kryteriów diagnostycznych. W prezentowanej pracy autorzy rozważają tezę, że przyczyną obu zaburzeń może być insulinooporność, będąca następstwem otyłości brzusznej. Ponadto dokonują przeglądu literatury dotyczącej występowania MS u kobiet z PCOS oraz omawiają wpływ wyboru określonych kryteriów diagnostycznych MS i PCOS na oszacowanie czêstoœci ich występowania.Both metabolic syndrome (MS) and polycystic ovary syndrome (PCOS) are common among women. The exact prevalence of MS in women with PCOS is dependent upon the diagnostic criteria used for each. However, the frequent co-occurrence of both MS and PCOS in women is suggestive of a common aetiology. In this short review article we argue that insulin resistance, as a consequence of abdominal obesity, may represent such a common aetiology. We also review the literature on the prevalence of MS in women with PCOS and consider the impact that the particular criteria used to diagnose both MS and PCOS may have had on these estimates of prevalence

Is the Bombali virus pathogenic in humans?

Motivation: The potential of the Bombali virus, a novel Ebolavirus, to cause disease in humans remains unknown. We have previously identified potential determinants of Ebolavirus pathogenicity in humans by analysing the amino acid positions that are differentially conserved (specificity 15 determining positions; SDPs) between human pathogenic Ebolaviruses and the non-pathogenic Reston virus. Here, we include the many Ebolavirus genome sequences that have since become available into our analysis and investigate the amino acid sequence of the Bombali virus proteins at the SDPs that discriminate between human pathogenic and non-human pathogenic Ebolaviruses. 20 Results: The use of 1408 Ebolavirus genomes (196 in the original analysis) resulted in a set of 166 SDPs (reduced from 180), 146 (88%) of which were retained from the original analysis. This indicates the robustness of our approach and refines the set of SDPs that distinguish human pathogenic Ebolaviruses from Reston virus. At SDPs, Bombali virus shared the majority of amino acids with the human pathogenic Ebolaviruses (63.25%). However, for two SDPs in VP24 (M136L, R139S) 25 that have been proposed to be critical for the lack of Reston virus human pathogenicity because they alter the VP24-karyopherin interaction, the Bombali virus amino acids match those of Reston virus. Thus, Bombali virus may not be pathogenic in humans. Supporting this, no Bombali virusassociated disease outbreaks have been reported, although Bombali virus was isolated from fruit bats cohabitating in close contact with humans, and anti-Ebolavirus antibodies that may indicate 30 contact with Bombali virus have been detected in humans

Risks Posed by Reston, the Forgotten Ebolavirus

Out of the five members of the Ebolavirus family, four cause lifethreatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans. Amino acid sequence differences between RESTV and the other Ebolaviruses are found in all nine Ebolavirus proteins, though no one residue appears sufficient to confer pathogenicity. Changes in the glycoprotein contribute to differences in Ebolavirus pathogenicity but are not sufficient to confer pathogenicity on their own. Similarly, differences in VP24 and VP35 affect viral immune evasion and are associated with changes in human pathogenicity. A recent in silico analysis systematically determined the functional consequences of sequence variations between RESTV and human-pathogenic Ebolaviruses. Multiple positions in VP24 were differently conserved between RESTV and the other Ebolaviruses and may alter human pathogenicity. In conclusion, the factors that determine the pathogenicity of Ebolaviruses in humans remain insufficiently understood. An improved understanding of these pathogenicity-determining factors is of crucial importance for disease prevention and for the early detection of emergent and potentially human-pathogenic RESTVs

Drug-Adapted Cancer Cell Lines as Preclinical Models of Acquired Resistance

Acquired resistance formation limits the efficacy of anti-cancer therapies. Acquired and intrinsic resistance differ conceptually. Acquired resistance is the consequence of directed evolution, whereas intrinsic resistance depends on the (stochastic) presence of pre-existing resistance mechanisms. Preclinical model systems are needed to study acquired drug resistance because they enable: (1) in depth functional studies; (2) the investigation of non-standard treatments for a certain disease condition (which is necessary to identify small groups of responders); and (3) the comparison of multiple therapies in the same system. Hence, they complement data derived from clinical trials and clinical specimens, including liquid biopsies. Many groups have successfully used drug-adapted cancer cell lines to identify and elucidate clinically relevant resistance mechanisms to targeted and cytotoxic anti-cancer drugs. Hence, we argue that drug-adapted cancer cell lines represent a preclinical model system in their own right that is complementary to other preclinical model systems and clinical data

Comparison of Drop Jump and Tuck Jump Knee Joint Kinematics in Elite Male Youth Soccer Players: Implications for Injury Risk Screening

Context: Despite the popularity of jump-landing tasks being used to identify injury risk factors, minimal data currently exist examining differences in knee kinematics during commonly used bilateral jumping tasks. This is especially the case for rebounding-based protocols involving young athletes. Objective: The purpose of this study was to compare the frontal plane projection angle (FPPA) during the drop vertical jump (DVJ) and tuck jump assessment (TJA) in a cohort of elite male youth soccer players of varying maturity status. Methods: A total of 57 male youth soccer players from an English championship soccer club participated in the study. Participants performed three trials of the DVJ and TJA, during which movement was recorded with two-dimensional video cameras. FPPA for both right (FPPA-r) and left (FPPA-l) legs, with values <180º indicative of medial knee displacement. Results: On a whole-group level, FPPA-r (172.7 ± 7.4 º versus 177.2 ± 11.7 º; p < 0.05; ES = 0.46) and FPPA-l (173.4 ± 7.3 º versus 179.2 ± 11.0 º; p < 0.05; ES = 0.62) was significantly greater for both limbs in the TJA compared to the DVJ; however, these differences were less consistent when grouped by maturity status. FPPA-r during the TJA was significantly and moderately greater in the circa-PHV group compared to the post-PHV cohorts (169.4 ± 6.4 º versus 175.3 ± 7.8 º; p < 0.05; ES = 0.49). Whole group data showed moderate relationships for FPPA-r and FPPA-l between the TJA and DVJ; however, stronger relationships were shown in circa and post-PHV players compared to the pre-PHV cohort. Conclusions: Considering that the TJA exposed players to a larger FPPA and was sensitive to between-group differences in FPPA-r, the TJA could be viewed as a more suitable screen for identifying FPPA in young male soccer players

Understanding of researcher behaviour is required to improve data reliability

Background: A lack of data reproducibility (“reproducibility crisis”) has been extensively debated across many academic disciplines. Main body: Although a reproducibility crisis is widely perceived, conclusive data on the scale of the problem and the underlying reasons are largely lacking. The debate is primarily focused on methodological issues. However, examples such as the use of misidentified cell lines illustrate that the availability of reliable methods does not guarantee good practice. Moreover, research is often characterised by a lack of established methods. Despite the crucial importance of researcher conduct, research and conclusive data on the determinants of researcher behaviour are widely missing. Conclusion: Meta-research is urgently needed that establishes an understanding of the factors that determine researcher behaviour. This knowledge can then be used to implement and iteratively improve measures, which incentivise researchers to apply the highest standards resulting in high quality data

Ebola outbreak highlights the need for wet and dry laboratory collaboration

The recent Ebola outbreak in Western Africa taught us that Ebolaviruses can cause much larger outbreaks and represent a much greater health threat than many of us believed (or wanted to believe). As of 30th March, the outbreak had resulted in 28,646 confirmed cases and 11,323 deaths. Although the WHO stated that the Ebola epidemic in West Africa no longer represents a Public Health Emergency of International Concern, since Guinea, Liberia, and Sierra are now capable of controlling and maintaining further small outbreaks, flare-ups still occur, most recently, on 4th April when two new cases were reported in Liberia (www.who.int)