Nonfunctional visual genes are usually associated with species that inhabit poor light environments (aquatic/subterranean/nocturnal), and these genes are believed to have lost function through relaxed selection acting on the visual system. Indeed, the visual system is so adaptive that the reconstruction of intact ancestral opsin genes has been used to reject nocturnality in ancestral primates. To test these assertions, we examined the functionality of the short and medium-to long-wavelength opsin genes in a group of mammals that are supremely adapted to a nocturnal niche: the bats. We sequenced the visual cone opsin genes in 33 species of bat with diverse sensory ecologies and reconstructed their evolutionary history spanning 65 million years. We found that, whereas the long-wave opsin gene was conserved in all species, the short-wave opsin gene has undergone dramatic divergence among lineages. The occurrence of gene defects in the short-wave opsin gene leading to loss of function was found to directly coincide with the origin of high-duty-cycle echolocation and changes in roosting ecology in some lineages. Our findings indicate that both opsin genes have been under purifying selection in the majority bats despite a long history of nocturnality. However, when spectacular losses do occur, these result from an evolutionary sensory modality tradeoff, most likely driven by subtle shifts in ecological specialization rather than a nocturnal lifestyle. Our results suggest that UV color vision plays a considerably more important role in nocturnal mammalian sensory ecology than previously appreciated and highlight the caveat of inferring light environments from visual opsins and vice versa.bats ͉ opsin gene ͉ sensory tradeoff ͉ echolocation ͉ selection V ision plays one of the most important roles in the survival of an individual, underpinning numerous key behaviors such as foraging, predator avoidance, and mate recognition. Color vision is conferred by the cone photopigments, each comprising an opsin transmembrane protein and a 11-cis-retinal chromophore (1, 2). Diversity in the properties and arrangement of photoreceptors in vertebrates reflects the evolutionary malleability of this system in response to specific visual challenges (3). Opsin proteins can be classified into medium/long wavelength sensitive (M/LWS) and short-wavelength-sensitive (SWS) based on the wavelength of their peak light sensitivity. Comparisons of visual pigments across taxa indicate that spectral tuning and, therefore, the wavelength of peak light sensitivity ( max ) are modulated by 5 key critical amino acid sites in M/LWS opsins (4) and at least 11-aa sites in SWS opsins (5).Most mammals possess both classes of opsin, with the M/LWS sensitive to green-red and the SWS1 sensitive to blue-violet (6), and a greater proportion of cones containing the former (85-95%) than the latter (only 5-15%) (3). Reported exceptions to this visual state include a number of monochromats, such as the blind mole rat (7), cetaceans (8), and the flying squirrel (9), ...

Propensity score matching is a method to reduce bias in non-randomized and observational studies. Propensity score matching is mainly applied to two treatment groups rather than multiple treatment groups, because some key issues affecting its application to multiple treatment groups remain unsolved, such as the matching distance, the assessment of balance in baseline variables, and the choice of optimal caliper width. The primary objective of this study was to compare propensity score matching methods using different calipers and to choose the optimal caliper width for use with three treatment groups. The authors used caliper widths from 0.1 to 0.8 of the pooled standard deviation of the logit of the propensity score, in increments of 0.1. The balance in baseline variables was assessed by standardized difference. The matching ratio, relative bias, and mean squared error (MSE) of the estimate between groups in different propensity score-matched samples were also reported. The results of Monte Carlo simulations indicate that matching using a caliper width of 0.2 of the pooled standard deviation of the logit of the propensity score affords superior performance in the estimation of treatment effects. This study provides practical solutions for the application of propensity score matching of three treatment groups.

BackgroundIn medical training, statistics is considered a very difficult course to learn and teach. Current studies have found that students’ attitudes toward statistics can influence their learning process. Measuring, evaluating and monitoring the changes of students’ attitudes toward statistics are important. Few studies have focused on the attitudes of postgraduates, especially medical postgraduates. Our purpose was to understand current attitudes regarding statistics held by medical postgraduates and explore their effects on students’ achievement. We also wanted to explore the influencing factors and the sources of these attitudes and monitor their changes after a systematic statistics course.MethodsA total of 539 medical postgraduates enrolled in a systematic statistics course completed the pre-form of the Survey of Attitudes Toward Statistics −28 scale, and 83 postgraduates were selected randomly from among them to complete the post-form scale after the course.ResultsMost medical postgraduates held positive attitudes toward statistics, but they thought statistics was a very difficult subject. The attitudes mainly came from experiences in a former statistical or mathematical class. Age, level of statistical education, research experience, specialty and mathematics basis may influence postgraduate attitudes toward statistics. There were significant positive correlations between course achievement and attitudes toward statistics. In general, student attitudes showed negative changes after completing a statistics course.ConclusionsThe importance of student attitudes toward statistics must be recognized in medical postgraduate training. To make sure all students have a positive learning environment, statistics teachers should measure their students’ attitudes and monitor their change of status during a course. Some necessary assistance should be offered for those students who develop negative attitudes.

Highlights d ORP4L is highly expressed in LSCs and essential for LSC survival d ORP4L extracts and presents PIP 2 from the plasma membrane for PLCb3 catalysis in LSCs d LYZ-81 is identified as a specific inhibitor of ORP4L

A chemotherapy regimen of docetaxel, doxorubicin and cyclophosphamide (TAC) has been accepted as a standard care because of their superior clinical benefit in early-stage breast cancer patients, but with a higher risk of neutropenia. Pegfilgrastim is a once-per-cycle therapy for prophylactic neutrophil support and neutropenia prevention. There was still a lack of direct evidences for finding an optimal fixed dose of pegfilgrastim in Chinese breast cancer patients receiving TAC regimen. An open-label, randomized, phase II study was designed to compare the effects of pegfilgrastim with filgrastim. Eighteen centers in China enrolled 171 eligible female breast cancer patients with cycles of TAC chemotherapy treatment, randomized into four arms, received a single subcutaneous injection of pegfilgrastim (60, 100 or 120 µg/kg) per chemotherapy cycle or daily subcutaneous injections of filgrastim 5 µg/kg 24 h after chemotherapy. Efficacy and safety were analyzed. In ITT population, the mean duration of grade 3+ neutropenia (neutrophil count <1.0 × 10(9)/l) was 2.09, 1.53 and 1.73 days in patients who received pegfilgrastim 60, 100 and 120 µg/kg/cycle, respectively, and 1.69 days in patients who received 5 µg/kg/day filgrastim (P = 0.043). The incidence of grade 3+ neutropenia was 76, 83 and 74 % for doses of pegfilgrastim and 90 % for filgrastim (P = 0.409). The results for febrile neutropenia, time to neutrophil recovery and neutrophil profile were also not significantly different between arms. The safety profiles of pegfilgrastim and filgrastim were similar. A single dose of 100 µg/kg once-per-cycle administration of pegfilgrastim provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim in Chinese breast cancer patients receiving TAC chemotherapy.

White blood cell (WBC) count has been associated with diabetic risk, but whether the correlation is independent of other risk factors has hardly been studied. Moreover, very few such studies with large sample sizes have been conducted in Chinese. Therefore, we investigated the relationship between WBC count and glucose metabolism in china. We also examined the relevant variables of WBC count. A total of 9,697 subjects (mean age, 58.0 ± 9.1 years) were recruited. The subjects were classified into four groups, including subjects with normal glucose tolerance, isolated impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). We found that WBC count increased as glucose metabolism disorders exacerbated. WBC count was also positively correlated with waist hip ratio, body mass index, smoking, triglycerides, glycosylated haemoglobin A1c (HbA1c) and 2-h postprandial glucose. In addition, high density lipoprotein and the female gender were inversely correlated with WBC levels. In patients with previously diagnosed T2DM, the course of T2DM was not correlated with WBC count. Our findings indicate that elevated WBC count is independently associated with worsening of glucose metabolism in middle-aged and elderly Chinese. In addition, loss of weight, smoking cessation, lipid-modifying therapies, and control of postprandial plasma glucose and HbA1c may ameliorate the chronic low-grade inflammation.

Fluvirosaones A (1) and B (2), together with virosecurinine (3), were isolated from Flueggea virosa. Their structures were determined by physical, spectroscopic, and X-ray analysis and confirmed through comparison of the calculated and experimental C NMR and electronic circular dichroism (ECD) data. Compounds 1 and 2 represent the first examples of a pentacyclic Securinega alkaloid containing a pentacyclic system and an α,β-unsaturated ketone. Plausible biogenetic pathways of compounds 1 and 2 are proposed.

High-performance computing (HPC) has become a state strategic technology in a number of countries. One hypothesis is that HPC can accelerate biopharmaceutical innovation. Our experimental data demonstrate that HPC can significantly accelerate biopharmaceutical innovation by employing molecular dynamics-based virtual screening (MDVS). Without using HPC, MDVS for a 10K compound library with tens of nanoseconds of MD simulations requires years of computer time. In contrast, a state of the art HPC can be 600 times faster than an eight-core PC server is in screening a typical drug target (which contains about 40K atoms). Also, careful design of the GPU/CPU architecture can reduce the HPC costs. However, the communication cost of parallel computing is a bottleneck that acts as the main limit of further virtual screening improvements for drug innovations.