Transcriptomics of liver and muscle in Holstein cows genetically divergent for fertility highlight differences in nutrient partitioning and inflammation processes.

peer-reviewedBM and SC were funded by the Teagasc Walsh Fellowship Scheme. This project was supported by Teagasc (RMIS 6075) and DAFM grant 13/S/528 led by SB. CJC was funded under the Science Foundation Ireland (SFI) Stokes lecturer scheme (07/SK/B1236A).Background The transition between pregnancy and lactation is a major physiological change for dairy cows. Complex systemic and local processes involving regulation of energy balance, galactopoiesis, utilisation of body reserves, insulin resistance, resumption of oestrous cyclicity and involution of the uterus can affect animal productivity and hence farm profitability. Here we used an established Holstein dairy cow model of fertility that displayed genetic and phenotypic divergence in calving interval. Cows had similar genetic merit for milk production traits, but either very good genetic merit for fertility traits (‘Fert+’; n = 8) or very poor genetic merit for fertility traits (‘Fert-’; n = 8). We used RNA sequencing to investigate gene expression profiles in both liver and muscle tissue biopsies at three distinct time-points: late pregnancy, early lactation and mid lactation (-18, 1 and 147 days relative to parturition, respectively). Results We found 807 and 815 unique genes to be differentially expressed in at least one time-point in liver and muscle respectively, of which 79 % and 83 % were only found in a single time-point; 40 and 41 genes were found differentially expressed at every time-point indicating possible systemic or chronic dysregulation. Functional annotation of all differentially expressed genes highlighted two physiological processes that were impacted at every time-point in the study, These were immune and inflammation, and metabolic, lipid and carbohydrate-binding. Conclusion These pathways have previously been identified by other researchers. We show that several specific genes which are differentially regulated, including IGF-1, might impact dairy fertility. We postulate that an increased burden of reactive oxidation species, coupled with a chronic inflammatory state, might reduce dairy cow fertility in our model.Teagasc Walsh Fellowship ProgrammeDepartment of Agriculture, Food and the MarineScience Foundation Irelan

Celebrating 70 years of nursing and midwifery in NHS Scotland. [Exhibition]

This set of infographics were displayed together in an exhibition celebrating 70 years of nursing and midwifery in NHS Scotland. They highlight events and images covering each decade of the history of NHS Scotland, from the 1940s through to present day and beyond

Using Nodal Ratios to Predict Risk of Regional Recurrences in Patients Treated with Breast Conservation Therapy with 4 or More Positive Lymph Nodes

Purpose. The value of nodal ratios (NRs) as a prognostic variable in breast cancer is continually being demonstrated. The purpose of this study was to use NR in patients with ≥4+ nodes to assess a correlation of NR with regional (lymph node) recurrence. Methods. Inclusion criteria was ≥8 nodes dissected with ≥4+ nodes after breast conservation therapy. Of 1060 patients treated from 1975 to 2003 who had a minimum of 8 nodes dissected, 273 were node+; 56 patients had ≥4+ involved nodes and were the focus of this study. Nodal ratios were calculated for each patient and grouped into 3 categories: high (≥70%), intermediate (40%–69%) and low (<40%). Each nodal ratio was correlated with patterns of local, regional, and distant failures and OS. Results. Outcomes for the entire cohort were BRFS-83%, NRFS-93%, DMFS-61%, and OS 63% at 10 yrs. The OS, DMFS, and NRFS correlated with N2 (4–9 nodes+) versus N3 (≥10+) status but did not correlate with BRFS, as expected. When evaluating NR, 18 pts had high NR (>70%). Only 3 patients experienced nodal recurrences, all within previously radiated supraclavicular fields. All 3 in-field regional failures occurred in the N3 group of patients with NR >70%. All were treated with a single AP field prescribed to a dose of 46 Gy at a standard depth of 3 cm. Conclusions. In this group of N2/N3 patients treated with BCT, we were able to identify patients at high risk for regional failures as those with high NR of >70% and ≥10+ nodes. While these findings need to be reproduced in larger datasets, this group of patients with NR of >70% in 4 or more positive axillary lymph nodes may benefit from meticulous targeting of regional nodes, dose escalation, and/or more intensive systemic therapies

The evolution of sex ratio distorter suppression affects a 25 cM genomic region in the butterfly Hypolimnas bolina

Open Access ArticleSymbionts that distort their host's sex ratio by favouring the production and survival of females are common in arthropods. Their presence produces intense Fisherian selection to return the sex ratio to parity, typified by the rapid spread of host 'suppressor' loci that restore male survival/development. In this study, we investigated the genomic impact of a selective event of this kind in the butterfly Hypolimnas bolina. Through linkage mapping, we first identified a genomic region that was necessary for males to survive Wolbachia-induced male-killing. We then investigated the genomic impact of the rapid spread of suppression, which converted the Samoan population of this butterfly from a 100:1 female-biased sex ratio in 2001 to a 1:1 sex ratio by 2006. Models of this process revealed the potential for a chromosome-wide effect. To measure the impact of this episode of selection directly, the pattern of genetic variation before and after the spread of suppression was compared. Changes in allele frequencies were observed over a 25 cM region surrounding the suppressor locus, with a reduction in overall diversity observed at loci that co-segregate with the suppressor. These changes exceeded those expected from drift and occurred alongside the generation of linkage disequilibrium. The presence of novel allelic variants in 2006 suggests that the suppressor was likely to have been introduced via immigration rather than through de novo mutation. In addition, further sampling in 2010 indicated that many of the introduced variants were lost or had declined in frequency since 2006. We hypothesize that this loss may have resulted from a period of purifying selection, removing deleterious material that introgressed during the initial sweep. Our observations of the impact of suppression of sex ratio distorting activity reveal a very wide genomic imprint, reflecting its status as one of the strongest selective forces in nature.Natural Environment Research Council (NERC

Public Health Response to Imported Case of Poliomyelitis, Australia, 2007

Inactivated polio vaccine was offered, and the index case-patient and household contacts were quarantined

PTP-1B is an essential positive regulator of platelet integrin signaling

Outside-in integrin αIIbβ3 signaling is required for normal platelet thrombus formation and is triggered by c-Src activation through an unknown mechanism. In this study, we demonstrate an essential role for protein–tyrosine phosphatase (PTP)–1B in this process. In resting platelets, c-Src forms a complex with αIIbβ3 and Csk, which phosphorylates c-Src tyrosine 529 to maintain c-Src autoinhibition. Fibrinogen binding to αIIbβ3 triggers PTP-1B recruitment to the αIIbβ3–c-Src–Csk complex in a manner that is dependent on c-Src and specific tyrosine (tyrosine 152 and 153) and proline (proline 309 and 310) residues in PTP-1B. Studies of PTP-1B–deficient mouse platelets indicate that PTP-1B is required for fibrinogen-dependent Csk dissociation from αIIbβ3, dephosphorylation of c-Src tyrosine 529, and c-Src activation. Furthermore, PTP-1B–deficient platelets are defective in outside-in αIIbβ3 signaling in vitro as manifested by poor spreading on fibrinogen and decreased clot retraction, and they exhibit ineffective Ca2+ signaling and thrombus formation in vivo. Thus, PTP-1B is an essential positive regulator of the initiation of outside-in αIIbβ3 signaling in platelets

A systematic mapping review of the associations between pregnancy intentions and health-related lifestyle behaviours or psychological wellbeing

The aim of this study was to conduct a systematic mapping review of the literature that explored associations of pregnancy intentions with health-related lifestyle behaviours and psychological wellbeing before and during pregnancy. Six databases were searched (May 2017) for papers relating to pregnancy intentions, health-related lifestyle behaviours, and psychological wellbeing. The literature was mapped according to the preconception or pregnancy period; prospective or retrospective variable assessment; and reported lifestyle behaviours and psychological wellbeing outcomes. Of 19,430 retrieved records, 303 studies were eligible. Pregnancy intentions were considered during the preconception period in 103 studies (only 23 assessed prospectively), and during the pregnancy period in 208 studies (141 prospectively). Associations between pregnancy intention and preconception behaviours/psychological wellbeing were primarily reported for supplement use (n = 58) and were lacking for diet/exercise, and psychological factors. For behaviours/psychological wellbeing during pregnancy, associations with pregnancy intention were focused on prenatal care (n = 79), depression (n = 61), and smoking (n = 56) and were lacking for diet/exercise. Only 7 studies assessed pregnancy intentions with a validated tool. Despite a large body of literature, there were several methodological limitations identified, namely assessment of pregnancy intentions with non-validated measures and the reliance on retrospective assessment. Future primary studies are needed to fill gaps in our understanding regarding energy-balance-related behaviours. Future studies (including reviews/meta-analyses) should take care to address the noted limitations to provide a comprehensive and accurate understanding of the relationships between pregnancy intentions and health-related lifestyle behaviours and psychological wellbeing before and during pregnancy

Lifestyle and psychological factors associated with pregnancy intentions: findings from a Longitudinal Cohort Study of Australian women

BACKGROUND:Preconception is a critical time for the establishment of healthy lifestyle behaviours and psychological well-being to reduce adverse maternal and offspring outcomes. This study aimed to explore relationships between preconception lifestyle and psychological factors and prospectively assessed short- (currently trying to conceive) and long-term (future parenthood aspirations) pregnancy intentions. METHODS:Data from Wave 3 (age 25-30 years; n = 7656) and Wave 5 (age 31-36 years; n = 4735) from the Australian Longitudinal Study of Women's Health were used. Pregnancy intentions and parenthood aspirations were evaluated. Logistic regressions explored cross-sectional associations between demographic, lifestyle and psychological factors and pregnancy intentions/parenthood aspirations. RESULTS:In multivariable models, parity and marital status were associated consistently with pregnancy intentions and parenthood aspirations. Few lifestyle behaviours and no psychological factors were associated with pregnancy intentions. Alcohol intake was the only behaviour associated with aspirations to have a first child. Aspirations for a second/subsequent child were associated negatively with physical activity, sitting time, diet quality, lower anxiety and higher stress. CONCLUSIONS:It appears that women are not changing their behaviours when they form a decision to try to conceive. Interventions are needed that address women's preconception needs, to optimise lifestyle and improve health outcomes for women and their families.Briony Hill, Mathew Ling, Gita Mishra, Lisa J. Moran, Helena J. Teede, Lauren Bruce and Helen Skouteri