The Influence of Sequence Variability and Dimerization on Mannose Binding in Monocot Mannose Binding Lectins

Abstract Motivation. A model of the lectin from Aloe arborescens was built by homology modeling. Docking studies with mannose were performed on this model and the known crystal structures of monocot mannose binding lectins from snowdrop and garlic. On the basis of these results association of monomers to form dimers is found to be necessary for successful binding of mannose by site III of these lectins, by providing the fourth strand of the -sheet that is a supporting edge for the site. From an analysis of the carbohydrate binding sites (I, II and III) of the above lectins and the docking studies, the mannose binding site I of aloe lectin is predicted to retain the ability to bind mannose with all of the key residues involved in binding unchanged. Site II and III lose residues specific for hydrogen bonding and are predicted to be unable to bind mannose. Aloe lectin monomers are shown to be able to associate as dimers but docking is still unsuccessful in site III. Method. Protein homology modeling and AutoDock docking studies were used in this study. Results. A homology model of aloe lectin was created by both manual and automatic methods and its ability to bind the natural substrate mannose was assessed by docking studies using the genetic algorithm approach in the AutoDock program. The results of the docking studies were correlated with those on lectins for which X-ray crystal data is known and rationalized in terms of specific mutations in the aloe lectin binding sites. Conclusions. Aloe lectin is predicted to be able to bind mannose in its site I binding site, unable to bind in site II because of key residue mutations and also unable to bind in site III

Geochemical compositional controls on DNA strand breaks induced in in vitro cell-free assays by crushed rock powders from the Panasqueira mine area, Portugal

From Springer Nature via Jisc Publications RouterHistory: received 2019-12-15, accepted 2020-06-24, registration 2020-06-24, pub-electronic 2020-07-09, online 2020-07-09, pub-print 2021-07Publication status: PublishedFunder: Saudi Arabia Cultural Bureau in London; doi: http://dx.doi.org/10.13039/100012363Abstract: DNA strand breaks are a common form of DNA damage that can contribute to chromosomal instability or gene mutations. Such strand breaks may be caused by exposure to heavy metals. The aim of this study was to assess the level of DNA strand breaks caused by µm-scale solid particles of known chemical composition with elevated heavy metals/metalloids, notably arsenic, using an in vitro cell-free DNA plasmid scission assay. These samples were incubated with and without H2O2 to see whether damage occurs directly or indirectly through the Fenton reaction. Levels of DNA damage in the absence of H2O2 were < 10%, but in the presence of H2O2, all samples showed higher levels of damage ranging from 10 to 100% suggesting that damage was being incurred through the Fenton reaction. Using bivariate correlation analysis and multiple linear regression, manganese oxide (MnO), sulphur (S), copper (Cu), and zinc (Zn) concentrations in the particulates were found to be the most significant predictors of DNA damage. The mechanism of this DNA damage formation has yet to be thoroughly investigated but is hypothesised to be due to reactive oxygen species formation. Further work is required to assess the extent of contribution of reactive oxygen species to this DNA damage, but this study highlights the potential role of chemistry and/or mineralogy to the extent and/or nature of DNA damage caused by particulates

Spoken term detection ALBAYZIN 2014 evaluation: overview, systems, results, and discussion

The electronic version of this article is the complete one and can be found online at: http://dx.doi.org/10.1186/s13636-015-0063-8Spoken term detection (STD) aims at retrieving data from a speech repository given a textual representation of the search term. Nowadays, it is receiving much interest due to the large volume of multimedia information. STD differs from automatic speech recognition (ASR) in that ASR is interested in all the terms/words that appear in the speech data, whereas STD focuses on a selected list of search terms that must be detected within the speech data. This paper presents the systems submitted to the STD ALBAYZIN 2014 evaluation, held as a part of the ALBAYZIN 2014 evaluation campaign within the context of the IberSPEECH 2014 conference. This is the first STD evaluation that deals with Spanish language. The evaluation consists of retrieving the speech files that contain the search terms, indicating their start and end times within the appropriate speech file, along with a score value that reflects the confidence given to the detection of the search term. The evaluation is conducted on a Spanish spontaneous speech database, which comprises a set of talks from workshops and amounts to about 7 h of speech. We present the database, the evaluation metrics, the systems submitted to the evaluation, the results, and a detailed discussion. Four different research groups took part in the evaluation. Evaluation results show reasonable performance for moderate out-of-vocabulary term rate. This paper compares the systems submitted to the evaluation and makes a deep analysis based on some search term properties (term length, in-vocabulary/out-of-vocabulary terms, single-word/multi-word terms, and in-language/foreign terms).This work has been partly supported by project CMC-V2 (TEC2012-37585-C02-01) from the Spanish Ministry of Economy and Competitiveness. This research was also funded by the European Regional Development Fund, the Galician Regional Government (GRC2014/024, “Consolidation of Research Units: AtlantTIC Project” CN2012/160)

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

Vegan diets : practical advice for athletes and exercisers.

With the growth of social media as a platform to share information, veganism is becoming more visible, and could be becoming more accepted in sports and in the health and fitness industry. However, to date, there appears to be a lack of literature that discusses how to manage vegan diets for athletic purposes. This article attempted to review literature in order to provide recommendations for how to construct a vegan diet for athletes and exercisers. While little data could be found in the sports nutrition literature specifically, it was revealed elsewhere that veganism creates challenges that need to be accounted for when designing a nutritious diet. This included the sufficiency of energy and protein; the adequacy of vitamin B12, iron, zinc, calcium, iodine and vitamin D; and the lack of the long-chain n-3 fatty acids EPA and DHA in most plant-based sources. However, via the strategic management of food and appropriate supplementation, it is the contention of this article that a nutritive vegan diet can be designed to achieve the dietary needs of most athletes satisfactorily. Further, it was suggested here that creatine and β-alanine supplementation might be of particular use to vegan athletes, owing to vegetarian diets promoting lower muscle creatine and lower muscle carnosine levels in consumers. Empirical research is needed to examine the effects of vegan diets in athletic populations however, especially if this movement grows in popularity, to ensure that the health and performance of athletic vegans is optimised in accordance with developments in sports nutrition knowledge

The evaluation of the North Atlantic climate system in UKESM1 historical simulations for CMIP6

Earth System models enable a broad range of climate interactions that physical climate models are unable to simulate. However, the extent to which adding Earth System components changes or improves the simulation of the physical climate is not well understood. Here we present a broad multi-variate evaluation of the North Atlantic climate system in historical simulations of the UK Earth System Model (UKESM1) performed for CMIP6. In particular, we focus on the mean state and the decadal timescale evolution of important variables that span the North Atlantic Climate system. In general, UKESM1 performs well and realistically simulates many aspects of the North Atlantic climate system. Like the physical version of the model, we find that changes in external forcing, and particularly aerosol forcing, are an important driver of multi-decadal change in UKESM1, especially for Atlantic Multi-decadal Variability and the Atlantic Meridional Overturning Circulation. However, many of the shortcomings identified are similar to common biases found in physical climate models, including the physical climate model that underpins UKESM1. For example, the summer jet is too weak and too far poleward; decadal variability in the winter jet is underestimated; intra-seasonal stratospheric polar vortex variability is poorly represented; and Arctic sea ice is too thick. Forced shortwave changes may be also too strong in UKESM1, which, given the important role of historical aerosol forcing in shaping the evolution of the North Atlantic in UKESM1, motivates further investigation. Therefore, physical model development, alongside Earth System development, remains crucial in order to improve climate simulations

True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses

International audienceBACKGROUND: Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual. As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential. In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors. To correct for these "false interactions", methods accounting for parasite risk factors must be used. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we propose such a method for presence-absence data (i.e., serology). Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic. The method is termed "the corrected chi-square." Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes. Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten. Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses. CONCLUSIONS/SIGNIFICANCE: This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations

Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood