MicroRNA expression profiling of porcine mammary epithelial cells after challenge with Escherichia coli in vitro

Background Coliform mastitis is a symptom of postpartum dysgalactia syndrome (PDS), a multifactorial infectious disease of sows. Our previous study showed gene expression profile change after bacterial challenge of porcine mammary epithelial cells (PMECs). These mRNA expression changes may be regulated through microRNAs (miRNAs) which play critical roles in biological processes. Therefore, miRNA expression profile was investigated in PMECs. Results PMECs were isolated from three lactating sows and challenged with heat-inactivated potential mastitis-causing pathogen Escherichia coli (E. coli) for 3 h and 24 h, in vitro. At 3 h post-challenge with E. coli, target gene prediction identified a critical role of miRNAs in regulation of host immune responses and homeostasis of PMECs mediated by affecting pathways including cytokine binding (miR-202, miR-3277, miR-4903); IL-10/PPAR signaling (miR-3277, miR-4317, miR-548); and NF-ĸB/TNFR2 signaling (miR-202, miR-2262, miR-885-3p). Target genes of miRNAs in PMECs at 24 h were significantly enriched in pathways associated with interferon signaling (miR-210, miR-23a, miR-1736) and protein ubiquitination (miR-125, miR-128, miR-1280). Conclusions This study provides first large-scale miRNA expression profiles and their predicted target genes in PMECs after contact with a potential mastitis-causing E. coli strain. Both, highly conserved miRNAs known from other species as well as novel miRNAs were identified in PMECs, representing candidate predictive biomarkers for PDS. Time-dependent pathogen clearance suggests an important role of PMECs in inflammatory response of the first cellular barrier of the porcine mammary gland

Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU

Experience-Dependent Effects of Muscimol-Induced Hippocampal Excitation on Mnemonic Discrimination

Memory requires similar episodes with overlapping features to be represented distinctly, a process that is disrupted in many clinical conditions as well as normal aging. Data from humans have linked this ability to activity in hippocampal CA3 and dentate gyrus (DG). While animal models have shown the perirhinal cortex is critical for disambiguating similar stimuli, hippocampal activity has not been causally linked to discrimination abilities. The goal of the current study was to determine how disrupting CA3/DG activity would impact performance on a rodent mnemonic discrimination task. Rats were surgically implanted with bilateral guide cannulae targeting dorsal CA3/DG. In Experiment 1, the effect of intra-hippocampal muscimol on target-lure discrimination was assessed within subjects in randomized blocks. Muscimol initially impaired discrimination across all levels of target-lure similarity, but performance improved on subsequent test blocks irrespective of stimulus similarity and infusion condition. To clarify these results, Experiment 2 examined whether prior experience with objects influenced the effect of muscimol on target-lure discrimination. Rats that received vehicle infusions in a first test block, followed by muscimol in a second block, did not show discrimination impairments for target-lure pairs of any similarity. In contrast, rats that received muscimol infusions in the first test block were impaired across all levels of target-lure similarity. Following discrimination tests, rats from Experiment 2 were trained on a spatial alternation task. Muscimol infusions increased the number of spatial errors made, relative to vehicle infusions, confirming that muscimol remained effective in disrupting behavioral performance. At the conclusion of behavioral experiments, fluorescence in situ hybridization for the immediate-early genes Arc and Homer1a was used to determine the proportion of neurons active following muscimol infusion. Contrary to expectations, muscimol increased neural activity in DG. An additional experiment was carried out to quantify neural activity in naïve rats that received an intra-hippocampal infusion of vehicle or muscimol. Results confirmed that muscimol led to DG excitation, likely through its actions on interneuron populations in hilar and molecular layers of DG and consequent disinhibition of principal cells. Taken together, our results suggest disruption of coordinated neural activity across the hippocampus impairs mnemonic discrimination when lure stimuli are novel

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data

We are grateful to the families and individuals who took part in the GS:SFHS and UKB studies, and to all those involved in participant recruitment, data collection, sample processing and QC, including academic researchers, clinical staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/ 14/Z. We acknowledge with gratitude the financial support received from the Dr Mortimer and Theresa Sackler Foundation. This research has been conducted using the GS:SFHS and UK Biobank (project #4844) resources. GS:SFHS received core funding from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. UKB was established using funding from the Wellcome Trust, Medical Research Council, the Scottish Government Department of Health, and the Northwest Regional Development Agency. DJP, IJD, TCR and AMM are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). TCR is supported by Alzheimer's Scotland, through the Marjorie MacBeath bequest. Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged. We are grateful for the use of summary data from the International Genomics of Alzheimer's Project and the Major Depressive Disorder working group of the Psychiatric Genomics Consortium.Peer reviewedPublisher PD

Assessment and Etiology of Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder in Boys and Girls

Attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are more common in boys than girls. In this paper, we investigated whether the prevalence differences are attributable to measurement bias. In addition, we examined sex differences in the genetic and environmental influences on variation in these behaviors. Teachers completed the Conners Teacher Rating Scale-Revised:Short version (CTRS-R:S) in a sample of 800 male and 851 female 7-year-old Dutch twins. No sex differences in the factor structure of the CTRS-R:S were found, implying the absence of measurement bias. The heritabilities for both ADHD and ODD were high and were the same in boys and girls. However, partly different genes are expressed in boys and girls

3D diffractive imaging of nanoparticle ensembles using an X-ray laser

We report the 3D structure determination of gold nanoparticles (AuNPs) by X-ray single particle imaging (SPI). Around 10 million diffraction patterns from gold nanoparticles were measured in less than 100 hours of beam time, more than 100 times the amount of data in any single prior SPI experiment, using the new capabilities of the European X-ray free electron laser which allow measurements of 1500 frames per second. A classification and structural sorting method was developed to disentangle the heterogeneity of the particles and to obtain a resolution of better than 3 nm. With these new experimental and analytical developments, we have entered a new era for the SPI method and the path towards close-to-atomic resolution imaging of biomolecules is apparent

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank

Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6 and the Scottish Funding Council HR03006. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z. YZ acknowledges support from China Scholarship Council. IJD is supported by the Centre for Cognitive Ageing and Cognitive Epidemiology which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). AMMcI and T-KC acknowledges support from the Dr Mortimer and Theresa Sackler Foundation. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Ethics approval for the study was given by the NHS Tayside committee on research ethics (reference 05/S1401/8)Peer reviewedPublisher PD

Emotional reaction to diagnosis of infertility in Kuwait and successful clients' perception of nurses' role during treatment

<p>Abstract</p> <p>Background</p> <p>The unfulfilled desire of millions of infertile couples worldwide to have their own biological children results in emotional distress. This study evaluated the emotional reactions of couples attending a combined infertility clinic in Kuwait and successful clients' perception of nurses.</p> <p>Methods</p> <p>Quantitative and qualitative methods were used. The first phase was by structured interview using two standardized psychological scales: the 25-item Hopkins Symptom Checklist and Modified Fertility Adjustment Scale. Data were collected from 268 couples attending the combined infertility clinic, between October 2002 and September 2007. The second phase was a semi-structured interview of 10 clients who got pregnant following treatment. The interview explored their feelings and perception of the nurses' role. Interviews were transcribed verbatim and analyzed.</p> <p>Results</p> <p>The average duration of infertility was 4 years; 65.7% of the women and 76.1% of men suffered from primary infertility. Emotional reactions experienced were: anxiety in women (12.7%) and men (6%), depression in women (5.2%) and men (14.9%) and reduced libido in women (6.7%) and men (29.9%). Also in men, 14.9% experienced premature ejaculation, 5.2% weak ejaculation and 7.9% had impotence although 4.9% were transient. In the semi-structured interviews, the emotions expressed were similar and in addition to anger, feelings of devastation, powerlessness, sense of failure and frustration. In the survey, 12.7% of the men were found to show more anxiety than women (6%). Although all the 10 women interviewed confirmed they were anxious; only 4 of their partners were reported to be sad or anxious. Successful clients' perception of nurses' roles included nurses carrying out basic nursing procedures, communicating, educating about investigative and treatment procedures, providing emotional support by listening, encouraging, reassuring and being empathetic.</p> <p>Conclusions</p> <p>This study illuminates the emotional reactions of infertile clients. Fertility nurses in Kuwait can provide emotional support through communication. The need for additional and continuous training for nurses employed in fertility settings in Kuwait is paramount.</p