Statistical interaction modeling of bovine herd behaviors

While there has been interest in modeling the group behavior of herds or flocks, much of this work has focused on simulating their collective spatial motion patterns which have not accounted for individuality in the herd and instead assume a homogenized role for all members or sub-groups of the herd. Animal behavior experts have noted that domestic animals exhibit behaviors that are indicative of social hierarchy: leader/follower type behaviors are present as well as dominance and subordination, aggression and rank order, and specific social affiliations may also exist. Both wild and domestic cattle are social species, and group behaviors are likely to be influenced by the expression of specific social interactions. In this paper, Global Positioning System coordinate fixes gathered from a herd of beef cows tracked in open fields over several days at a time are utilized to learn a model that focuses on the interactions within the herd as well as its overall movement. Using these data in this way explores the validity of existing group behavior models against actual herding behaviors. Domain knowledge, location geography and human observations, are utilized to explain the causes of these deviations from this idealized behavior

Comparative genomic analysis of a multidrug-resistant Staphylococcus hominis ShoR14 clinical isolate from Terengganu, Malaysia, led to the discover of novel mobile genetic elements

Staphylococcus hominis is a coagulase-negative Staphylococcus (CoNS) commensal capable of causing serious systemic infections in humans. The emergence of multidrug-resistant S. hominis strains is of concern but little is known about the characteristics of this organism, particularly from Malaysia. Here, we present the comparative genome analysis of S. hominis ShoR14, a multidrugresistant, methicillin-resistant blood isolate from Terengganu, Malaysia. Genomic DNA of S. hominis ShoR14 was sequenced on the Illumina platform and assembled using Unicycler v0.4.8. ShoR14 belonged to sequence type (ST) 1 which is the most prevalent ST of the S. hominis subsp. hominis. Comparative genomic analysis with closely related strains in the database with complete genome sequences, led to the discovery of a novel variant of the staphylococcal chromosome cassette mec (SCCmec) type VIII element harboring the mecA methicillin-resistance gene in ShoR14 and its possible carriage of a SCCfus element that encodes the fusidic acid resistance gene (fusC). Up to seven possible ShoR14 plasmid contigs were identified, three of which harbored resistance genes for tetracycline (tetK), chloramphenicol (catA7), macrolides, lincosamides, and streptogramin B (ermC). Additionally, we report the discovery of a novel mercury-resistant transposon, Tn7456, other genomic islands, and prophages which make up the S. hominis mobilome

Construction of challenging proline–proline junctions via diselenide–selenoester ligation chemistry

Polyproline sequences are highly abundant in prokaryotic 10 and eukaryotic proteins, where they serve as key components of 11 secondary structure. To date, construction of the proline−proline motif 12 has not been possible owing to steric congestion at the ligation junction, 13 together with an n → π* electronic interaction that reduces the 14 reactivity of acylated proline residues at the C-terminus of peptides. 15 Here, we harness the enhanced reactivity of prolyl selenoesters and a 16 trans-γ-selenoproline moiety to access the elusive proline−proline 17 junction for the first time through a diselenide−selenoester ligation− 18 deselenization manifold. The efficient nature of this chemistry is 19 highlighted in the high-yielding one-pot assembly of two proline-rich 20 polypeptide targets, submaxillary gland androgen regulated protein 3B 21 and lumbricin-1. This method provides access to the most challenging of ligation junctions, thus enabling the construction of 22 previously intractable peptide and protein targets of increasing structural complexity

Processing of Nonconjugative Resistance Plasmids by Conjugation Nicking Enzyme of Staphylococci

ABSTRACT Antimicrobial resistance in Staphylococcus aureus presents an increasing threat to human health. This resistance is often encoded on mobile plasmids, such as pSK41; however, the mechanism of transfer of these plasmids is not well understood. In this study, we first examine key protein-DNA interactions formed by the relaxase enzyme, NES, which initiates and terminates the transfer of the multidrug resistance plasmid pSK41. Two loops on the NES protein, hairpin loops 1 and 2, form extensive contacts with the DNA hairpin formed at the oriT region of pSK41, and here we establish that these contacts are essential for proper DNA cleavage and religation by the full 665-residue NES protein in vitro . Second, pSK156 and pCA347 are nonconjugative Staphylococcus aureus plasmids that contain sequences similar to the oriT region of pSK41 but differ in the sequence predicted to form a DNA hairpin. We show that pSK41-encoded NES is able to bind, cleave, and religate the oriT sequences of these nonconjugative plasmids in vitro . Although pSK41 could mobilize a coresident plasmid harboring its cognate oriT , it was unable to mobilize plasmids containing the pSK156 and pCA347 variant oriT mimics, suggesting that an accessory protein like that previously shown to confer specificity in the pWBG749 system may also be involved in transmission of plasmids containing a pSK41-like oriT . These data indicate that the conjugative relaxase in trans mechanism recently described for the pWBG749 family of plasmids also applies to the pSK41 family of plasmids, further heightening the potential significance of this mechanism in the horizontal transfer of staphylococcal plasmids. IMPORTANCE Understanding the mechanism of antimicrobial resistance transfer in bacteria such as Staphylococcus aureus is an important step toward potentially slowing the spread of antimicrobial-resistant infections. This work establishes protein-DNA interactions essential for the transfer of the Staphylococcus aureus multiresistance plasmid pSK41 by its relaxase, NES. This enzyme also processed variant oriT -like sequences found on numerous plasmids previously considered nontransmissible, suggesting that in conjunction with an uncharacterized accessory protein, these plasmids may be transferred horizontally via a relaxase in trans mechanism. These findings have important implications for our understanding of staphylococcal resistance plasmid evolution

Complete genome sequence and analysis of a ST573 multidrug-resistant methicillin-resistant Staphylococcus aureus SauR3 clinical isolate from Terengganu, Malaysia

Methicillin-resistant Staphylococcus aureus (MRSA) is aWorld Health Organization-listed priority pathogen. Scarce genomic data are available for MRSA isolates from Malaysia. Here, we present the complete genome sequence of a multidrug-resistant MRSA strain SauR3, isolated from the blood of a 6-year-old patient hospitalized in Terengganu, Malaysia, in 2016. S. aureus SauR3 was resistant to five antimicrobial classes comprising nine antibiotics. The genome was sequenced on the Illumina and Oxford Nanopore platforms and hybrid assembly was performed to obtain its complete genome sequence. The SauR3 genome consists of a circular chromosome of 2,800,017 bp and three plasmids designated pSauR3-1 (42,928 bp), pSauR3-2 (3011 bp), and pSauR3-3 (2473 bp). SauR3 belongs to sequence type 573 (ST573), a rarely reported sequence type of the staphylococcal clonal complex 1 (CC1) lineage, and harbors a variant of the staphylococcal cassette chromosome mec (SCCmec) type V (5C2&5) element which also contains the aac(60)-aph(200) aminoglycoside-resistance genes. pSauR3-1 harbors several antibiotic resistance genes in a 14,095 bp genomic island (GI), previously reported in the chromosome of other staphylococci. pSauR3-2 is cryptic, whereas pSauR3-3 encodes the ermC gene that mediates inducible resistance to macrolide-lincosamide-streptogramin B (iMLSB). The SauR3 genome can potentially be used as a reference genome for other ST573 isolates

On the Normalization of the Neutrino-Deuteron Cross Section

As is well-known, comparison of the solar neutrino fluxes measured in SuperKamiokande (SK) by $\nu + e^- \to \nu + e^-$ and in the Sudbury Neutrino Observatory (SNO) by $\nu_e + d \to e^- + p + p$ can provide a ``smoking gun'' signature for neutrino oscillations as the solution to the solar neutrino puzzle. This occurs because SK has some sensitivity to all active neutrino flavors whereas SNO can isolate electron neutrinos. This comparison depends crucially on the normalization and uncertainty of the theoretical charged-current neutrino-deuteron cross section. We address a number of effects which are significant enough to change the interpretation of the SK--SNO comparison.Comment: 4 pages, 1 figure, submitted to PR

Solar and atmospheric neutrino oscillations with three flavours

We analyze the solar and the atmospheric neutrino problems in the context of three flavour neutrino oscillations. We assume a mass hierarchy in the vacuum mass eigenvalues $\mu_3^2 \gg \mu_2^2 \geq \mu_1^2$, but make no approximation regarding the magnitudes of the mixing angles. We find that there are small but continuous bands in the parameter space where the constraints imposed by the current measurements of $\ {}^{71} Ga$, ${}^{37} Cl$ and Kamiokande experiments are satisfied at $1 \sigma$ level. The allowed parameter space increases dramatically if the error bars are enlarged to $1.6 \sigma$. The electron neutrino survival probability has different energy dependence in different regions of the parameter space. Measurement of the recoil electron energy spectrum in detectors that use $\nu - e$ scattering may distinguish between some of the allowed regions of parameter space. Finally we use the results for the parameter space admitted by the solar neutrinos as an input for the atmospheric neutrino problem and show that there exists a substantial region of parameter space in which both problems can be solved.Comment: 25 pages plus eight figures. Uses Revtex. Postcript files for figures sent separately as a uuencoded fil

Early-life inflammatory markers and subsequent psychotic and depressive episodes between 10 to 28 years of age

Inflammation is implicated in depression and psychosis, including association of childhood inflammatory markers on the subsequent risk of developing symptoms. However, it is unknown whether early-life inflammatory markers are associated with the number of depressive and psychotic symptoms from childhood to adulthood. Using the prospective Avon Longitudinal Study of Children and Parents birth cohort (N = up-to 6401), we have examined longitudinal associations of early-life inflammation [exposures: interleukin-6 (IL-6), C-reactive protein (CRP) levels at age 9y; IL-6 and CRP DNA-methylation (DNAm) scores at birth and age 7y; and IL-6 and CRP polygenic risk scores (PRSs)] with the number of depressive episodes and psychotic experiences (PEs) between ages 10–28 years. Psychiatric outcomes were assessed using the Short Mood and Feelings Questionnaire and Psychotic Like Symptoms Questionnaires, respectively. Exposure-outcome associations were tested using negative binomial models, which were adjusted for metabolic and sociodemographic factors. Serum IL-6 levels at age 9y were associated with the total number of depressive episodes between 10 and 28y in the base model (n = 4835; β = 0.066; 95%CI:0.020–0.113; pFDR = 0.041) which was weaker when adjusting for metabolic and sociodemographic factors. Weak associations were observed between inflammatory markers (serum IL-6 and CRP DNAm scores) and total number of PEs. Other inflammatory markers were not associated with depression or PEs. Early-life inflammatory markers are associated with the burden of depressive episodes and of PEs subsequently from childhood to adulthood. These findings support a potential role of early-life inflammation in the aetiology of depression and psychosis and highlight inflammation as a potential target for treatment and prevention

Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach.

BACKGROUND: Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene-environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene-environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health. METHODS: We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene-environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions. FINDINGS: Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24-1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene-environment correlation but did not show the absence of passive gene-environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration). INTERPRETATION: Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment. Family-based analyses point to a role of active and reactive gene-environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects. FUNDING: Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre.This work was supported by the Wellcome Trust (Grant refs: 214322/Z/18/Z, 104036/Z/14/Z, 204623/Z/16/Z, and 217065/Z/19/Z). VW was funded by the Bowring Research Fellowship from St. Catharine’s College, Cambridge and Wellcome Trust Collaborative Award (Grant Ref: 214322/Z/18/Z). ASFK and AM are supported by Wellcome Trust Grant 104036/Z/14/Z. ASFK is also supported by an ESRC Postdoctoral Fellowship (Grant ref: ES/V011650/1). ML is supported by the scholarship from the China Scholarship Council (No. 201706990036). The work of CC has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No 707404 and grant agreement No 848158 (EarlyCause Project). MHvIJ is supported by the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development) and by a Spinoza Prize of the Netherlands Organization for Scientific Research. HMS and MRM are supported by the Medical Research Council and the University of Bristol (MC_UU_00011/7) and by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol. HMS is also supported by the European Research Council (Grant ref: 758813 MHINT). CMN is supported by the National Institute for Mental Health NIMH R01MH106595 and the Center of Excellence for Stress and Mental Health (CESAMH), Veterans Affairs San Diego. AJG and SB are supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204623/Z/16/Z). TMM and RB are supported by the NIMH (R01MH117014, TMM; K23MH120437, RB).The research was conducted in association with the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, and the NIHR Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. This research was possible due to two applications to the UK Biobank: Projects 20904 and 23787. This research was co-funded by the NIHR Cambridge Biomedical Research Centre and a Marmaduke Sheild grant. The UK Medical Research Council and Wellcome (Grant Ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The study website contains details of all data available through a fully searchable data dictionary (http://www.bristol.ac.uk/alspac/researchers/our-data/). Part of this data was collected using REDCap, see the REDCap website for details https://projectredcap.org/resources/citations/). The first phase of the Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam; the Erasmus University Rotterdam; ZonMw; the Netherlands Organization for Scientific Research (NWO); and the Ministry of Health, Welfare and Sport. The authors gratefully acknowledge the contribution of all children and parents, general practitioners, hospitals, midwives and pharmacies involved in the Generation R Study. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Erasmus School of Social and Behavioural Sciences at Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare Foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam