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Background:Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined.Materials and Methods:Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, β-oxidation, lipolysis and cysteine oxidation.Results:Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery.Conclusions:These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The concept of autonomous farming concerns automatic agricultural machines operating safely and efficiently without human intervention. In order to ensure safe autonomous operation, real-time risk detection and avoidance must be undertaken. This paper presents a flexible vehicle-mounted sensor system for recording positional and imaging data with a total of six sensors, and a full procedure for calibrating and registering all sensors. Authentic data were recorded for a case study on grass-harvesting and human safety. The paper incorporates parts of ISO 18497 (an emerging standard for safety of highly automated machinery in agriculture) related to human detection and safety. The case study investigates four different sensing technologies and is intended as a dataset to validate human safety or a human detection system in grass-harvesting. The study presents common algorithms that are able to detect humans, but struggle to handle lying or occluded humans in high grass.

During the last decades, high-efficiency farming equipment has been developed in the agricultural sector. This has also included efficiency improvement of moving techniques, which include increased working speeds and widths. Therefore, the risk of wild animals being accidentally injured or killed during routine farming operations has increased dramatically over the years. In particular, the nests of ground nesting bird species like grey partridge (Perdix perdix) or pheasant (Phasianus colchicus) are vulnerable to farming operations in their breeding habitat, whereas in mammals, the natural instinct of e.g., leverets of brown hare (Lepus europaeus) and fawns of roe deer (Capreolus capreolus) to lay low and still in the vegetation to avoid predators increase their risk of being killed or injured in farming operations. Various methods and approaches have been used to reduce wildlife mortality resulting from farming operations. However, since wildlife-friendly farming often results in lower efficiency, attempts have been made to develop automatic systems capable of detecting wild animals in the crop. Here we assessed the suitability of thermal imaging in combination with digital image processing to automatically detect a chicken (Gallus domesticus) and a rabbit (Oryctolagus cuniculus) in a grassland habitat. Throughout the different test scenarios, our study animals were detected with a high precision, although the most dense grass cover reduced the detection rate. We conclude that thermal imaging and digital imaging processing may be an important tool for the improvement of wildlife-friendly farming practices in the future.

Since human-wildlife conflicts are increasing, the development of cost-effective methods for reducing damage or conflict levels is important in wildlife management. A wide range of devices to detect and deter animals causing conflict are used for this purpose, although their effectiveness is often highly variable, due to habituation to disruptive or disturbing stimuli. Automated recognition of behaviours could form a critical component of a system capable of altering the disruptive stimuli to avoid this. In this paper we present a novel method to automatically recognise goose behaviour based on vocalisations from flocks of free-living barnacle geese (Branta leucopsis). The geese were observed and recorded in a natural environment, using a shielded shotgun microphone. The classification used Support Vector Machines (SVMs), which had been trained with labeled data. Greenwood Function Cepstral Coefficients (GFCC) were used as features for the pattern recognition algorithm, as they can be adjusted to the hearing capabilities of different species. Three behaviours are classified based in this approach, and the method achieves a good recognition of foraging behaviour (86–97% sensitivity, 89–98% precision) and a reasonable recognition of flushing (79–86%, 66–80%) and landing behaviour(73–91%, 79–92%). The Support Vector Machine has proven to be a robust classifier for this kind of classification, as generality and non-linearcapabilities are important. We conclude that vocalisations can be used to automatically detect behaviour of conflict wildlife species, and as such, may be used as an integrated part of awildlife management system.

A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions. The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation. Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression. IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.

Konrad Hochedlinger and colleagues show that ascorbic acid enhances cellular reprogramming by preventing hypermethylation of the imprinted Dlk1 - Dio3 locus. They use this approach to generate adult mice derived entirely from induced pluripotent stem cells obtained through reprogramming of terminally differentiated B cells. The generation of induced pluripotent stem cells (iPSCs) often results in aberrant epigenetic silencing of the imprinted Dlk1 - Dio3 gene cluster, compromising the ability to generate entirely iPSC-derived adult mice ('all-iPSC mice'). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1 - Dio3 by enabling a chromatin configuration that interferes with binding of the de novo DNA methyltransferase Dnmt3a. This approach allowed us to generate all-iPSC mice from mature B cells, which have until now failed to support the development of exclusively iPSC-derived postnatal animals. Our data show that transcription factor–mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that culture conditions during cellular reprogramming can strongly influence the epigenetic and biological properties of the resultant iPSCs.

DNMT3L, a regulatory factor related in sequence to DNA methyltransferases, is shown to interact with the N terminus of histone H3 and this interaction is inhibited by methylation at lysine 4. This suggests DNMT3L could respond to states of histone modification to regulate de novo DNA methylation. Mammals use DNA methylation for the heritable silencing of retrotransposons and imprinted genes and for the inactivation of the X chromosome in females. The establishment of patterns of DNA methylation during gametogenesis depends in part on DNMT3L, an enzymatically inactive regulatory factor that is related in sequence to the DNA methyltransferases DNMT3A and DNMT3B 1 , 2 . The main proteins that interact in vivo with the product of an epitope-tagged allele of the endogenous Dnmt3L gene were identified by mass spectrometry as DNMT3A2, DNMT3B and the four core histones. Peptide interaction assays showed that DNMT3L specifically interacts with the extreme amino terminus of histone H3; this interaction was strongly inhibited by methylation at lysine 4 of histone H3 but was insensitive to modifications at other positions. Crystallographic studies of human DNMT3L showed that the protein has a carboxy-terminal methyltransferase-like domain and an N-terminal cysteine-rich domain. Cocrystallization of DNMT3L with the tail of histone H3 revealed that the tail bound to the cysteine-rich domain of DNMT3L, and substitution of key residues in the binding site eliminated the H3 tail–DNMT3L interaction. These data indicate that DNMT3L recognizes histone H3 tails that are unmethylated at lysine 4 and induces de novo DNA methylation by recruitment or activation of DNMT3A2.

Animal-based studies indicate that bisphenol A (BPA) exposure is detrimental to reproductive health, but its impact on the earliest stages of germ cell development remains poorly defined. Using a murine model of early germ cell specification and differentiation, we sought to assess whether exposure to low levels of BPA prior to formation of primordial germ cells (PGCs) alters their differentiation trajectory and unique molecular program. We used an established method of differentiation of mouse embryonic stem cells (ESCs) into epiblast-like cells (EpiLCs) followed by PGC-like cells (PGCLCs), which together recapitulate defined stages of early germ cell development. Cellular consequences were determined using hemocytometer-based cell counting, fixation, and intracellular staining, followed by flow cytometry/fluorescence-activated cell sorting (FACS) of cells exposed to increasing concentrations (range: ) of BPA. To interrogate and characterize gene expression differences resulting from BPA exposure, we also generated RNA-seq libraries from RNA extracted from FACS-purified PGCLCs and performed transcriptome analysis using bioinformatics-based approaches. Exposure of EpiLCs to BPA resulted in higher numbers of cells that were associated with a higher proportion of cells in S-phase as well as a lower proportion undergoing apoptosis; this difference occurred in a concentration-dependent manner. Exposure also resulted in a greater fraction of EpiLCs showing signs of DNA damage. Remarkably, EpiLC exposure did not negatively affect PGC specification and resulted in a concentration-dependent effect on PGCLC proliferation in XX but not XY cells. PGCLC transcriptome analysis revealed an aberrant program with significant deregulation of X-linked genes and retrotransposon expression. Differential gene expression analysis also revealed the deregulation of genes associated with lipid metabolism as well as deregulated expression of genes associated with later stages of gametogenesis. To the best of our knowledge our findings represent the first characterization of the consequences of early BPA exposure on a model of mammalian PGC development, highlighting altered cell behavior, altered underlying pathways, and altered molecular processes. https://doi.org/10.1289/EHP8196.

Background and aims:Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor α (anti-TNFα) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis.Methods:Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data.Results:For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity.Conclusion:Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-)response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis.ClinicalTrials.gov number, NCT00639821.