T-Cell Responses to the M3 Immune Evasion Protein of Murid Gammaherpesvirus 68 Are Partially Protective and Induced with Lytic Antigen Kinetics

DNA vaccination with the M3 gene, encoding an immune evasion molecule expressed during both the acute lytic and persistent phases of murid gammaherpesvirus 68 infection, yielded a significantly lower titer of virus in the lung than controls. The protection seen was dependent on T cells, and we mapped an epitope recognized by CD8 T cells. The immune response to this epitope follows the same kinetics as lytic cycle antigens, despite the fact that this gene is expressed in both lytic and persistent stages of infection. This has important implications for our understanding of T-cell responses to putative latency-associated gammaherpesvirus proteins and how vaccination may improve control of these viruses

Implications of climate change for managing urban green infrastructure in Indiana

Urban areas around the world are increasingly investing in networks of urban forests, gardens, and other forms of green infrastructure for its many benefits, including enhanced livability, sustainability, and climate change mitigation and adaptation. Proactive planning for climate change requires anticipating potential climate change impacts to green infrastructure and adjusting management strategies accordingly. We apply climate change projections for Indiana to assess the possible impacts of climate change on common forms of urban green infrastructure, and identify management implications. Projected changes in Indiana’s temperature and precipitation could pose numerous management challenges for managing urban green infrastructure, including water stress; pests, weeds, disease and invasive species; flooding; frost risk; and timing of maintenance. Meeting these challenges will involve managing for key characteristics of resilient systems (e.g. biodiversity, redundancy) as well as more specific strategies addressing particular climate changes (e.g. shifting species compositions, building soil water holding capacity). Climate change also presents opportunities to promote urban green infrastructure. Unlike human built infrastructure, green infrastructure is conducive to grassroots stewardship and governance, relieving climate change-related strains on municipal budgets. Many online resources for adapting urban green infrastructure to climate change are already available, and emerging research will enhance understanding of best management practices

Stress and eating behaviors

Studies pertaining to obesity, stress, and their impact on organizations are plentiful. Further, there is an abundance of research surrounding stress at work and eating behaviors. However, studies regarding work stress and fasting are absent. Because of this, our study aims to examine the relationship between stress, fasting behaviors, and interoception. Interoception is the perception of physical (body) sensations, such as hunger. We argue that interoceptive awareness will mediate the positive relationships between stress and fasting behavior. We argue that stress fasting behaviors are likely to occur during periods of high stress, such as balancing work and midterm exams. Therefore, we propose to gather data from working college students to test our hypotheses

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138837/1/cncr30802.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138837/2/cncr30802_am.pd

Lactation and neonatal nutrition: defining and refining the critical questions.

This paper resulted from a conference entitled "Lactation and Milk: Defining and refining the critical questions" held at the University of Colorado School of Medicine from January 18-20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond

Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers

Muscle glycogen utilisation during Rugby match play: Effects of pre-game carbohydrate

Objectives: Although the physical demands of Rugby League (RL) match-play are well-known, the fuel sources supporting energy-production are poorly understood. We therefore assessed muscle glycogen utilisation and plasma metabolite responses to RL match-play after a relatively high (HCHO) or relatively low CHO (LCHO) diet. Design: Sixteen (mean ± SD age; 18 ± 1 years, body-mass; 88 ± 12 kg, height 180 ± 8 cm) professional players completed a RL match after 36-h consuming a non-isocaloric high carbohydrate (n = 8; 6 g kg day−1) or low carbohydrate (n = 8; 3 g kg day−1) diet. Methods: Muscle biopsies and blood samples were obtained pre- and post-match, alongside external and internal loads quantified using Global Positioning System technology and heart rate, respectively. Data were analysed using effects sizes ±90% CI and magnitude-based inferences. Results: Differences in pre-match muscle glycogen between high and low carbohydrate conditions (449 ± 51 and 444 ± 81 mmol kg−1 d.w.) were unclear. High (243 ± 43 mmol kg−1 d.w.) and low carbohydrate groups (298 ± 130 mmol kg−1 d.w.) were most and very likely reduced post-match, respectively. For both groups, differences in pre-match NEFA and glycerol were unclear, with a most likely increase in NEFA and glycerol post-match. NEFA was likely lower in the high compared with low carbohydrate group post-match (0.95 ± 0.39 mmol l−1 and 1.45 ± 0.51 mmol l−1, respectively), whereas differences between the 2 groups for glycerol were unclear (98.1 ± 33.6 mmol l−1 and 123.1 ± 39.6 mmol l−1) in the high and low carbohydrate groups, respectively. Conclusions: Professional RL players can utilise ∼40% of their muscle glycogen during a competitive match regardless of their carbohydrate consumption in the preceding 36-h

A Core Outcome Set for the Benefits and Adverse Events of Bariatric and Metabolic Surgery:the BARIACT project

BackgroundBariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this. Here, we present the development of a COS for BARIAtric and metabolic surgery Clinical Trials-the BARIACT Study.Methods and findingsOutcomes identified from systematic reviews and patient interviews informed a questionnaire survey. Patients and health professionals were surveyed three times and asked to rate the importance of each item on a 1-9 scale. Delphi methods provided anonymised feedback to participants. Items not meeting predefined criteria were discarded between rounds. Remaining items were discussed at consensus meetings, held separately with patients and professionals, where the COS was agreed. Data sources identified 2,990 outcomes, which were used to develop a 130-item questionnaire. Round 1 response rates were moderate but subsequently improved to above 75% for other rounds. After rounds 2 and 3, 81 and 14 items were discarded, respectively, leaving 35 items for discussion at consensus meetings. The final COS included nine items: "weight," "diabetes status," "cardiovascular risk," "overall quality of life (QOL)," "mortality," "technical complications of the specific operation," "any re-operation/re-intervention," "dysphagia/regurgitation," and "micronutrient status." The main limitation of this study was that it was based in the United Kingdom only.ConclusionsThe COS is recommended to be used as a minimum in all trials of bariatric and metabolic surgery. Adoption of the COS will improve data synthesis and the value of research data. Future work will establish methods for the measurement of the outcomes in the COS

Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study

Objectives To measure the effect of the adverse events within 35 days of transrectal ultrasound guided biopsy from the perspective of asymptomatic men having prostate specific antigen (PSA) testing; to assess early attitude to re-biopsy; to estimate healthcare resource use associated with adverse events due to biopsy; and to develop a classification scheme for reporting adverse events after prostate biopsy

A rare variant in EZH2 is associated with prostate cancer risk

Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genome sequencing was performed in a large PrCa family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), was identified as segregating with disease in all but two individuals in the family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10−5). Transcriptome analysis was performed on prostate tumour needle biopsies available for two rare variant carriers and two wild-type cases. Although no allele-dependent differences were detected in EZH2 transcripts, a distinct differential gene expression signature was observed when comparing prostate tissue from the rare variant carriers with the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB and EGR1, which were subsequently validated by qPCR. These data provide evidence that rs78589034 is associated with increased PrCa risk in Tasmanian men and further, that this variant may be associated with perturbed EZH2 function in prostate tissue. Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including prostate, and is of significant interest as a therapeutic target