Predicting gene expression in the human malaria parasite Plasmodium falciparum using histone modification, nucleosome positioning, and 3D localization features.

Empirical evidence suggests that the malaria parasite Plasmodium falciparum employs a broad range of mechanisms to regulate gene transcription throughout the organism's complex life cycle. To better understand this regulatory machinery, we assembled a rich collection of genomic and epigenomic data sets, including information about transcription factor (TF) binding motifs, patterns of covalent histone modifications, nucleosome occupancy, GC content, and global 3D genome architecture. We used these data to train machine learning models to discriminate between high-expression and low-expression genes, focusing on three distinct stages of the red blood cell phase of the Plasmodium life cycle. Our results highlight the importance of histone modifications and 3D chromatin architecture in Plasmodium transcriptional regulation and suggest that AP2 transcription factors may play a limited regulatory role, perhaps operating in conjunction with epigenetic factors

Tissue Destruction Resulting from the Interaction of Cytotoxic T Cells and Their Targets a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73703/1/j.1749-6632.1988.tb36330.x.pd

Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni

BACKGROUND: Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. RESULTS: We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1, cytoplasmic intermediate filament (IF) protein and transcription enzymes such as elongation factor 1α and EF-2. CONCLUSION: Production of the first cDNA microarray for profiling gene expression in B. glabrata provides a foundation for expanding our understanding of pathways and genes involved in the snail internal defence system (IDS). We demonstrate resistant strain-specific expression of genes potentially associated with the snail IDS, ranging from signalling and inflammation responses through to lysis of proteinacous products (encapsulated sporocysts or phagocytosed parasite components) and processing/degradation of these targeted products by ubiquitination

Ageing well in older men in Otago and Southland of New Zealand: a focus group study protocol

Background: Men in New Zealand (NZ) do not enjoy the same level of health and wellbeing as women. Men generally experience a higher incidence of, and mortality from, major diseases; most importantly, life expectancies for men in NZ are approximately four years less than for women. Such disparities vary across rural and urban communities, and across ethnic sub-groups. In particular, Māori men live some seven years less than other NZ men. Despite such inequalities, men’s health is not recognised as a priority by healthcare providers, government, or at the wider societal level. This qualitative study seeks to address this, by contributing to our understanding of factors associated with health and wellbeing for men in the ageing process. Study findings will also inform the development of a national survey of older men. Method: Focus groups will be used to explore the expectations and experiences of health and wellbeing in a cohort of older men (≥45 years) in the Otago and Southland regions. Topics to be explored will include gender role conflict, health service help-seeking, lifestyle behaviours, social engagement, and self-identified health risks. In total, five groups are planned (6-10 men per group) and will be conducted in urban, rural, and urban-rural adjunct areas. Focus groups will be recorded, and transcribed verbatim. Transcriptions will be coded for themes using the abductive thematic analysis approach. Results: This paper presents a protocol of a study in progress, and results are not yet known. Discussion: This is the first qualitative study focussing on ageing well in men in NZ. It will contribute to our understanding of this aspect of men’s health, and–ultimately–help to inform interventions and policies to better support men to age positively

Men’s Health Research in New Zealand: A Scoping Review

Background: Globally, there has been a growing awareness of the health challenges faced by men. The current public health agenda in Aotearoa New Zealand (NZ) does not specifically address the needs of men. The aim of this scoping review was to capture the major health issues facing men in NZ and particularly to identify the knowledge gaps in the understanding of men’s health within the NZ context. This was achieved by presenting key data on their health status and systematically mapping research in NZ related to men’s health; international data are also referenced for context as relevant. Method: A search and screening of the literature were conducted using Ovid, Web of Science and Scopus databases from January 1996 to July 2021, with advice from a medical librarian. Search terms included “men’s/male’s health” and “men’s/male’s health NZ.” An environmental scan of international literature was also carried out and information from the Ministry of Health and Statistics NZ was obtained to provide context of the status of research on men’s health in NZ. Main Findings: In keeping with international literature, the major health issues for men in NZ are life-limiting diseases including cancer and cardiovascular disease, the spread of overweight and obesity, issues with masculinity and help-seeking behaviours, unhealthy lifestyles, mental health issues and poor health literacy. The main areas of research related to men’s health from the NZ literature were highlighted. Discussion: Men’s health remains an under-recognised issue in NZ. If we are to address current inequities in health for men, clinicians, researchers and relevant agencies need to pay more attention to men’s health issues and take up the challenge to highlight and promote men’s health status in NZ

Detection of the heavy Higgs boson at γγ\gamma\gamma colliders

We consider the possibility of detecting a heavy Higgs boson ($m_H>2m_Z$) in proposed $\gamma\gamma$ colliders through the semi-leptonic mode $\gamma\gamma \rightarrow H \rightarrow ZZ \rightarrow q\bar q \ell^+\ell^-$. We show that due to the non-monochromatic nature of the photon beams produced by the laser-backscattering method, the resultant cross section for Higgs production is much smaller than the on-resonance cross section and generally {\it decreases} with increasing collider energy. Although continuum $ZZ$ production is expected to be negligible, we demonstrate the presence of and calculate sizeable backgrounds from $\gamma\gamma\rightarrow \ell^+\ell^-Z,\,q\bar qZ$, with $Z\rightarrow q\bar q,\,\ell^+\ell^-$, respectively, and $\gamma\gamma\rightarrow t\bar t\rightarrow b\bar b\ell^+\ell^-\nu\bar\nu$. This channel may be used to detect a Higgs of mass $m_H$ up to around 350~GeV at a 0.5~TeV $e^+e^-$ collider, assuming a nominal yearly luminosity of 10--20~fb$^{-1}$.Comment: 18 pages (in RevTeX) plus Postscript figures (available by email or FAX), NUHEP-TH-92-29 and DOE-309-CPP-47. (Revised version: NO CHANGES to the manuscript, simply removed corrupted figure files

Notes on Notebooks: Is Jupyter the Bringer of Jollity?

As the interactive computational notebook becomes a more prominent code development medium, we examine advantages and disadvantages of this particular source code format. We specify the structure of a coding notebook layout. We describe complexities in notebook programming; some of these are incidental whereas others may be inherent complexities. We outline how we envisage research and development might proceed to advance the cause of notebook programming

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients

Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826Not peer reviewedPublisher PD