The bovine alveolar macrophage DNA methylome is resilient to infection with Mycobacterium bovis

DNA methylation is pivotal in orchestrating gene expression patterns in various mammalian biological processes. Perturbation of the bovine alveolar macrophage (bAM) transcriptome, due to Mycobacterium bovis (M. bovis) infection, has been well documented; however, the impact of this intracellular pathogen on the bAM epigenome has not been determined. Here, whole genome bisulfite sequencing (WGBS) was used to assess the effect of M. bovis infection on the bAM DNA methylome. The methylomes of bAM infected with M. bovis were compared to those of non-infected bAM 24 hours post-infection (hpi). No differences in DNA methylation (CpG or non-CpG) were observed. Analysis of DNA methylation at proximal promoter regions uncovered >250 genes harbouring intermediately methylated (IM) promoters (average methylation of 33-66%). Gene ontology analysis, focusing on genes with low, intermediate or highly methylated promoters, revealed that genes with IM promoters were enriched for immune-related GO categories; this enrichment was not observed for genes in the high or low methylation groups. Targeted analysis of genes in the IM category confirmed the WGBS observation. This study is the first in cattle examining genome-wide DNA methylation at single nucleotide resolution in an important bovine cellular host-pathogen interaction model, providing evidence for IM promoter methylation in bAM

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

Effect of increasing dietary energy density during late gestation and lactation on sow performance, piglet vitality, and lifetime growth of offspring

peer-reviewedGenetic selection for hyperprolificacy in sows has resulted in a significant increase in the number of piglets born alive per litter but subsequently, decreased piglet vitality and growth. As a consequence, increasing sows’ energy intake during lactation to help increase piglet vitality and growth is increasingly important. The objective of this study was to investigate the effect of increasing dietary energy density for lactating sows on weight and back-fat changes in sows, milk composition, and vitality and growth of progeny. Gestating sows (N = 100; Large White × Landrace) were randomly assigned to one of four energy dense diets at day 108 of gestation until subsequent service; 13.8 (LL), 14.5 (L), 15.2 (H), and 15.9 MJ DE/kg (HH). All diets contained 1.2% total lysine. Blood samples from sows were taken on day 108 of gestation and at weaning (day 26 of lactation) and colostrum (day 0) and milk samples (day 14) were collected during lactation. Sow lactation feed intakes were recorded daily. The number of piglets born per litter (total and live), piglet birth weight (total and live), intrauterine growth restriction (IUGR) traits and muscle tone were recorded in piglets at birth. Piglet tympanic ear temperature (TEMP) was recorded at birth and at 24 h. Pigs were weighed on days 1, 6, 14, 26, 33, 40, 54, 75, and 141 of life. Postweaning (PW) pigs were fed standard cereal-based diets. Pig carcass data were collected at slaughter (day 141). Lactation energy intake was higher for HH sows than for all other treatments (P < 0.01). Colostrum and milk composition and lactation feed intake were not affected by treatment. The number of piglets born per litter (total and live) and piglet birthweight (total and live) was similar between treatments. Piglets from LL sows had more IUGR traits (P < 0.01), while those from HH sows had better muscle tone (P < 0.01) than all other treatments. Piglets from LL sows (P < 0.01) and piglets from H sows (P < 0.01) had a higher 24 h TEMP than piglets from HH sows. H sows weaned a greater number of piglets than L sows (P < 0.05) and HH sows (P < 0.01), while L sows weaned lighter litters than H (P < 0.05) and LL sows (P < 0.05). Pig growth PW was unaffected by treatment. High energy dense diets increased energy intake in sows, without depressing appetite. Feeding an HH diet improved piglet muscle tone at birth, whereas feeding an H diet increased litter size at weaning. Inconsistent results were observed for other traits of piglet vitality and for preweaning litter growth performance

The Exhibition as an Experiment: An Analogy and its Implications

The analogy of the exhibition as an experiment suggests innovative curatorial approaches that challenge institutional practices. This analogy has however a historical precedence in modernism when itbecame paradigmatic of the exhibitions at the Museum of ModernArt in New York in the 1940s, defining the curatorial approach of its founding director Alfred J Barr. This article considers this early useof the analogy of the exhibition as an experiment and further reflects on its redefinition at the turn of the 20th century by examining how both the notions of the exhibition and of the experiment havechanged over time. In particular, the article examines the different meanings and practices inferred by the concepts of the exhibition and the experiment in the first decades of the 20th century and in the present. It outlines how correspondences between cultural and scientific paradigms can be deployed to tease unacknowledged synergies between two modes of knowledge production (i.e. the art exhibition and the experiment) and address questions of presentness, authority and legitimacy that they imply

Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains

Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0 +/- 3.0% accuracy, with a time delay of 1.59 +/- 1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.open12

Pavlovian Reward Prediction and Receipt in Schizophrenia: Relationship to Anhedonia

Reward processing abnormalities have been implicated in the pathophysiology of negative symptoms such as anhedonia and avolition in schizophrenia. However, studies examining neural responses to reward anticipation and receipt have largely relied on instrumental tasks, which may confound reward processing abnormalities with deficits in response selection and execution. 25 chronic, medicated outpatients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging using a Pavlovian reward prediction paradigm with no response requirements. Subjects passively viewed cues that predicted subsequent receipt of monetary reward or non-reward, and blood-oxygen-level-dependent signal was measured at the time of cue presentation and receipt. At the group level, neural responses to both reward anticipation and receipt were largely similar between groups. At the time of cue presentation, striatal anticipatory responses did not differ between patients and controls. Right anterior insula demonstrated greater activation for nonreward than reward cues in controls, and for reward than nonreward cues in patients. At the time of receipt, robust responses to receipt of reward vs. nonreward were seen in striatum, midbrain, and frontal cortex in both groups. Furthermore, both groups demonstrated responses to unexpected versus expected outcomes in cortical areas including bilateral dorsolateral prefrontal cortex. Individual difference analyses in patients revealed an association between physical anhedonia and activity in ventral striatum and ventromedial prefrontal cortex during anticipation of reward, in which greater anhedonia severity was associated with reduced activation to money versus no-money cues. In ventromedial prefrontal cortex, this relationship held among both controls and patients, suggesting a relationship between anticipatory activity and anhedonia irrespective of diagnosis. These findings suggest that in the absence of response requirements, brain responses to reward receipt are largely intact in medicated individuals with chronic schizophrenia, while reward anticipation responses in left ventral striatum are reduced in those patients with greater anhedonia severity

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

Background: Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods: We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results: Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions: We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli

Systematic review of pre-operative exercise in colorectal cancer patients

The aim of this systematic review was to evaluate the evidence for exercise interventions prior to surgery for colorectal cancer resection. The evidence for use of exercise to improve physical fitness and surgical outcomes is as yet unknown. A systematic search was performed of MEDLINE, EMBASE, CINAHL, AMED and BNI databases for studies involving pre-operative exercise in colorectal cancer patients. Eight studies were included in the review. There is evidence that pre-operative exercise improves functional fitness, and to a lesser extent objectively measurable cardio-respiratory fitness prior to colorectal cancer resection. There is no clear evidence at present that this improvement in fitness translates into reduced peri-operative risk or improved post-operative outcomes. Current studies are limited by risk of bias. This review highlights the common difficulty in transferring promising results in a research setting, into significant improvements in the clinical arena. Future research should focus on which type of exercise is most likely to maximise patient adherence and improvements in cardio-respiratory fitness. Ultimately, adequately powered, randomised controlled trials are needed to investigate whether pre-operative exercise improves post-operative morbidity and mortality

Marine Functional Foods Research Initiative (NutraMara)

Sea Change—A Marine Knowledge, Research & Innovation Strategy for Ireland 2007-2013—was launched in early 2007 and was the outcome of extensive analysis and consultation with government departments, state agencies, industry and the third-level sector. It outlines a vision for the development of Ireland’s marine sector and sets clear objectives aimed at achieving this vision, namely to: 1. Assist existing, and largely indigenous, marine sub-sectors to improve their overall competitiveness and engage in activity that adds value to their outputs by utilising knowledge and technology arising from research. 2. Build new research capacity and capability and utilise fundamental knowledge and technology to create new marine-related commercial opportunities and companies. 3. Inform public policy, governance and regulation by applying the knowledge derived from marine research and monitoring. 4. Increase the marine sector’s competitiveness and stimulate the commercialisation of the marine resource in a manner that ensures its sustainability and protects marine biodiversity and ecosystems. 5. Strengthen the economic, social and cultural base of marine dependant regional/rural communities. The Sea Change strategy was developed as an integral part of the government’s Strategy for Science, Technology and Innovation (SSTI) and the Marine Institute as the lead implementation agency is working within SSTI policy and with government departments and agencies to deliver on the Strategy. The Marine Institute managed Marine Research Sub-Programme, one of eight sub-programmes within the Science, Technology and Innovation (STI) Programme of the National Development Plan 2007—2013, targets funding to meet the objectives of the Sea Change strategy. Over the lifetime of Sea Change, funding will be provided for: • Project-Based Awards o Strategic Research Projects o Applied Research Projects o Demonstration Projects o Desk/Feasibility Studies • Researcher Awards o Strategic Research Appointments o Research Capacity/Competency Building o Post-Doctoral Fellowships o PhD Scholarships • Industry-Led Research Awards o Company Awards o Collaborative Awards • Infrastructure Awards o Infrastructure Acquisition o Access to InfrastructurNutraMara – Marine Functional Foods Research Initiative: The goal was to create new research capacity and build the capabilities required to maximise the potential of Ireland’s extensive marine bioresources. By supporting a strong interdisciplinary research team, capable of exploring marine animals and plants as a sustainable source of materials for use as functional ingredients and foods, the vision for NutraMara was to position Ireland to the fore in use of marine bioresources as health beneficial ingredients.Lead Partner: Teagasc – The Irish Food and Agriculture Authority Project Partners: National University of Ireland Galway University College Dublin University of Limerick Ulster University University College Cor

An overview of Irish pig production, research and knowledge transfer since 1960

peer-reviewedPig production in Ireland has gone through enormous changes during the past 60 yr, from pigs being primarily produced as a sideline on dairy farms, to an industry with one of the highest average herd sizes in Europe. This happened in part due to external pressure on the industry, whereby economies of scale were needed to compete with pigs produced in other countries, but largely due to the instigation of national programmes to support the pig industry through research, education and knowledge transfer. These efforts helped producers to take advantage of genetic improvements and monitor their own performance over time, as well as allowing for benchmarking of the national herd against other countries. The research programme initiated in the 1960s continues to grow and expand, providing the pig industry with internationally renowned data and knowledge in the areas of nutrition, animal welfare, the environment and energy use. Recent initiatives such as the establishment of the Teagasc and Irish Farmers Association Pig Joint Programme, and a Pig Health Check section in Animal Health Ireland, will help to promote further cross-collaboration between stakeholders in the pig industry, and enable it to rise to the challenges of the years ahead