Stable isotope (δD–δ¹⁸O) relationships of ice facies and glaciological structures within the mid-latitude maritime Fox Glacier, New Zealand

Relationships between stable isotopes (δD–δ¹⁸O), ice facies and glacier structures have hitherto gone untested in the mid-latitude maritime glaciers of the Southern Hemisphere. Here, we present δD–δ¹⁸O values as part of a broader study of the structural glaciology of Fox Glacier, New Zealand. We analyzed 94 samples of δD–δ¹⁸O from a range of ice facies to investigate whether isotopes have potential for structural glaciological studies of a rapidly deforming glacier. The δD–δ¹⁸O measurements were aided by structural mapping and imagery from terminus time-lapse cameras. The current retreat phase was preceded by an advance of 1 km between 1984 and 2009, with the isotopic sampling and analysis undertaken at the end of that advance (2010/11). Stable isotopes from debris-bearing shear planes near the terminus, interpreted as thrust faults, are isotopically enriched compared with the surrounding ice. When plotted on co-isotopic diagrams (δD–δ¹⁸O), ice sampled from the shear planes appears to show a subtle, but distinctive isotopic signal compared with the surrounding clean ice on the lower glacier. Hence, stable isotopes (δD–δ¹⁸O) have potential within the structural glaciology field, but larger sample numbers than reported here may be required to establish isotopic contrasts between a broad range of ice facies and glacier structures

Maximising the value of transmitted data from PSATs tracking marine fish: a case study on Atlantic bluefin tuna

This is the final version. Available from BMC via the DOI in this record. Availability of data and materials: The data sets generated and analysed during the current study are not publicly available due to funder restrictions but may be available from the corresponding author on reasonable request.Background: The use of biologging tags to answer questions in animal movement ecology has increased in recent decades. Pop-up satellite archival tags (PSATs) are often used for migratory studies on large fish taxa. For PSATs, movements are normally reconstructed from variable amounts of transmitted data (unless tags are recovered, and full data archives accessed) by coupling geolocation methods with a state-space modelling (SSM) approach. Between 2018 and 2019, we deployed Wildlife Computers PSATs (MiniPATs) from which data recovery varied considerably. This led us to examine the effect of PSAT data volume on SSM performance (i.e., variation in reconstructed locations and their uncertainty). We did this by comparing movements reconstructed using partial ( 1000 km); (ii) for fish that travelled long distances, mean distance of locations from corresponding complete data set locations were inversely correlated with the volume of data received; (iii) if only 5% of data was used for geolocation, reconstructed locations for long-distance fish differed by 2213 ± 647 km from the locations derived from complete data sets; and, (iv) track reconstructions omitted migrations into the Mediterranean Sea if less than 30% of data was used for geolocation. Conclusions: For Wildlife Computers MiniPATs in our specific application, movements reconstructed with as little as 30% of the total geolocation data results in plausible outputs from the GPE3. Below this data volume, however, significant differences of more than 2000 km can occur. Whilst for a single species and manufacturer, this highlights the importance of careful study planning and the value of conducting study-specific sensitivity analysis prior to inclusion of modelled locations in research outputs. Based on our findings, we suggest general steps and refinements to maximise the value of light geolocation data from PSATs deployed on aquatic animals and highlight the importance of conducting data sensitivity analyses.European Maritime and Fisheries FundDepartment for Environment, Food and Rural Affairs (UK

The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial

Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015

From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

Tracking Atlantic bluefin tuna from foraging grounds off the west coast of Ireland

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordPop-up archival tags (n=16) were deployed on Atlantic bluefin tuna off the west coast of Ireland in October and November 2016 (199 to 246cm Curved Fork Length, CFL), yielding 2799 days of location data and 990 and 989 days of depth and temperature time-series data respectively, including downloaded archives from three recovered tags. Most daily locations (96%, n=2,651) occurred east of 45°W, the current stock management boundary for Atlantic bluefin tuna. Key open ocean habitats occupied were the Bay of Biscay and the Central North Atlantic, with two migratory patterns evident: an east-west group and an eastern resident group. Five out of six tags that remained attached until July 2017 returned to the northeast Atlantic after having migrated as far as the Canary Islands, the Mediterranean Sea and the Central North Atlantic. Tracked bluefin tuna exhibited a diel depth-use pattern occupying shallower depths at night and deeper depths during the day. Four bluefin tuna visited known spawning grounds in the central and western Mediterranean Sea, and one may have spawned, based on recovered data showing oscillatory dives transecting the thermocline on 15 nights. These findings demonstrate the complexity of the aggregation of Atlantic bluefin tuna off Ireland and, more broadly in the northeast Atlantic, highlighting the need for dedicated future research to conserve this important aggregation.European Maritime and Fisheries FundU.K. Department for Farming Fisheries and Rural Affair

Evidence of increased occurrence of Atlantic bluefin tuna in territorial waters of the United Kingdom and Ireland

This is the final version. Available on open access from Oxford University Press via the DOI in this recordData availability: Where applicable available data sources are linked in text. Where not specifically referred to in-text, data are subject to inter-organization data-sharing agreements and/or GDPR restrictions. Consequently, data requests will be processed on a case-by-case basis by the authors.Atlantic bluefin tuna (ABT, Thunnus thynnus; Linneaus, 1758) is an ecologically important apex-predator with high commercial value. They were once common off the coast of the United Kingdom (UK), before disappearing in the 1960s. In regions lacking commercial fisheries for ABT, such as the UK and Ireland, spatial data can be scarce. In these cases, sightings and bycatch databases can offset information shortfalls. Here, we document the reappearance of ABT into territorial waters of the UK from 2014 onwards, and increased occurrence off Ireland. We analyse a novel, multi-source dataset comprising occurrence data (2008–2019; 989 sightings and 114 tonnes of bycatch) compiled from a range of sources (scientific surveys, ecotours and fisheries). We show an increasing trend in effort-corrected ABT occurrence in (i) the pelagic ecosystem survey in the western English Channel and Celtic Sea (PELTIC), (ii) an ecotour operator, and (iii) the Irish albacore fishery in on-shelf and off-shelf waters. Sightings of ABT by the PELTIC correlated with modelled abundance estimates of ABT and the Atlantic multidecadal oscillation. These data demonstrate that sightings of ABT have increased off the UK and Ireland since 2014, following the same increasing trend (2010 onwards) as the eastern ABT population.University of ExeterEuropean Maritime and Fisheries FundDepartment for Environment, Food and Rural Affairs (DEFRA)NOAA Bluefin Tuna Research ProgramTag-A-Giant Fund (TAG

HLA-A Confers an HLA-DRB1 Independent Influence on the Risk of Multiple Sclerosis

A recent high-density linkage screen confirmed that the HLA complex contains the strongest genetic factor for the risk of multiple sclerosis (MS). In parallel, a linkage disequilibrium analysis using 650 single nucleotide polymorphisms (SNP) markers of the HLA complex mapped the entire genetic effect to the HLA-DR-DQ subregion, reflected by the well-established risk haplotype HLA-DRB1*15,DQB1*06. Contrary to this, in a cohort of 1,084 MS patients and 1,347 controls, we show that the HLA-A gene confers an HLA-DRB1 independent influence on the risk of MS (P = 8.4×10−10). This supports the opposing view, that genes in the HLA class I region indeed exert an additional influence on the risk of MS, and confirms that the class I allele HLA-A*02 is negatively associated with the risk of MS (OR = 0.63, P = 7×10−12) not explained by linkage disequilibrium with class II. The combination of HLA-A and HLA-DRB1 alleles, as represented by HLA-A*02 and HLA-DRB1*15, was found to influence the risk of MS 23-fold. These findings imply complex autoimmune mechanisms involving both the regulatory and the effector arms of the immune system in the triggering of MS

Sequences, Annotation and Single Nucleotide Polymorphism of the Major Histocompatibility Complex in the Domestic Cat

Two sequences of major histocompatibility complex (MHC) regions in the domestic cat, 2.976 and 0.362 Mbps, which were separated by an ancient chromosome break (55–80 MYA) and followed by a chromosomal inversion were annotated in detail. Gene annotation of this MHC was completed and identified 183 possible coding regions, 147 human homologues, possible functional genes and 36 pseudo/unidentified genes) by GENSCAN and BLASTN, BLASTP RepeatMasker programs. The first region spans 2.976 Mbp sequence, which encodes six classical class II antigens (three DRA and three DRB antigens) lacking the functional DP, DQ regions, nine antigen processing molecules (DOA/DOB, DMA/DMB, TAPASIN, and LMP2/LMP7,TAP1/TAP2), 52 class III genes, nineteen class I genes/gene fragments (FLAI-A to FLAI-S). Three class I genes (FLAI-H, I-K, I-E) may encode functional classical class I antigens based on deduced amino acid sequence and promoter structure. The second region spans 0.362 Mbp sequence encoding no class I genes and 18 cross-species conserved genes, excluding class I, II and their functionally related/associated genes, namely framework genes, including three olfactory receptor genes. One previously identified feline endogenous retrovirus, a baboon retrovirus derived sequence (ECE1) and two new endogenous retrovirus sequences, similar to brown bat endogenous retrovirus (FERVmlu1, FERVmlu2) were found within a 140 Kbp interval in the middle of class I region. MHC SNPs were examined based on comparisons of this BAC sequence and MHC homozygous 1.9× WGS sequences and found that 11,654 SNPs in 2.84 Mbp (0.00411 SNP per bp), which is 2.4 times higher rate than average heterozygous region in the WGS (0.0017 SNP per bp genome), and slightly higher than the SNP rate observed in human MHC (0.00337 SNP per bp)

Early and Prolonged Antiretroviral Therapy Is Associated with an HIV-1-Specific T-Cell Profile Comparable to That of Long-Term Non-Progressors

Background: Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs).Methodology/Principal Findings: We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-gamma, IL-2, TNF-alpha production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8+ T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden.Conclusions: Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption

Variation analysis and gene annotation of eight MHC haplotypes: The MHC Haplotype Project

The human major histocompatibility complex (MHC) is contained within about 4 Mb on the short arm of chromosome 6 and is recognised as the most variable region in the human genome. The primary aim of the MHC Haplotype Project was to provide a comprehensively annotated reference sequence of a single, human leukocyte antigen-homozygous MHC haplotype and to use it as a basis against which variations could be assessed from seven other similarly homozygous cell lines, representative of the most common MHC haplotypes in the European population. Comparison of the haplotype sequences, including four haplotypes not previously analysed, resulted in the identification of >44,000 variations, both substitutions and indels (insertions and deletions), which have been submitted to the dbSNP database. The gene annotation uncovered haplotype-specific differences and confirmed the presence of more than 300 loci, including over 160 protein-coding genes. Combined analysis of the variation and annotation datasets revealed 122 gene loci with coding substitutions of which 97 were non-synonymous. The haplotype (A3-B7-DR15; PGF cell line) designated as the new MHC reference sequence, has been incorporated into the human genome assembly (NCBI35 and subsequent builds), and constitutes the largest single-haplotype sequence of the human genome to date. The extensive variation and annotation data derived from the analysis of seven further haplotypes have been made publicly available and provide a framework and resource for future association studies of all MHC-associated diseases and transplant medicine