The growth and reproduction of the freshwater limpet Burnupia stenochorias (Pulmonata, Ancylidae), and an evaluation of its use as an ecotoxicology indicator in whole effluent testing

For the protection of the ecological Reserve in South Africa, the proposed introduction of compulsory toxicity testing in the licensing of effluent discharges necessitates the development of whole effluent toxicity testing. The elucidation of the effects of effluent on the local indigenous populations of organisms is essential before hazard and risk assessment can be undertaken. The limpet Burnupia stenochorias, prevalent in the Eastern Cape of South Africa, was chosen to represent the freshwater molluscs as a potential toxicity indicator. Using potassium dichromate (as a reference toxicant) and a textile whole effluent, the suitability of B. stenochorias was assessed under both acute and chronic toxicity conditions in the laboratory. In support of the toxicity studies, aspects of the biology of B. stenochorias were investigated under both natural and laboratory conditions. Using Principal Component and Discriminant Function Analyses, the relative shell morphometrics of three feral populations of B. stenochorias were found to vary. Length was shown to adequately represent growth of the shell, although the inclusion of width measurements is more statistically preferable. Two of the feral populations, one in impacted water, were studied weekly for 52 weeks to assess natural population dynamics. Based on the Von Bertalanffy Growth Equation, estimates of growth and longevity were made for this species, with growth highly seasonal. Age is not easily discerned from shell size. Egg laying occurred all year round, with early summer (peak egg lay), mid summer (a second, smaller peak in egg lay), and winter (limited presence of eggs) phases. In toxicity testing, consideration is given to the choice of the test organism based on age and sexual development. Consequently, the sexual development of B. stenochorias relative to shell length was determined with the aid of histological examinations of transverse sections of limpets, of all sizes, collected over one year. Limpets less than 3mm shell length were found to be immature in the development of the oocytes and spermatozoa, and were later chosen for acute toxicity tests. A laboratory diet was developed, for both culturing and maintaining of the limpets during toxicity tests; however, the diet requires optimisation. Under laboratory conditions, growth was linear, and individual fecundity highly variable. Successful methods for the collection of limpets from naturally occurring populations, and their acclimation to the laboratory were developed. Three B. stenochorias populations, representing different hydrological and water quality conditions, were compared to a laboratory population (maintained for three years) in their responses to the textile whole effluent and potassium dichromate. Under acute conditions, variability of mortality between limpet populations and between seasons was consistent with acceptable international standards. However, seasonal differences between feral limpets were apparent, with early summer limpets significantly more susceptible to both potassium dichromate and textile effluent than winter limpets. Although mortality occurred within the effluent at all concentrations, no 96 hour LC₅₀ values were obtained. The chronic toxicity effects of the textile whole effluent were assessed over the entire life cycle of B. stenochorias, based on survival, growth and reproductive effects. Lower concentrations of effluent (# 10%) gave greater variability of responses and toxicity than higher concentrations, with a 43 day LC₅₀ of 3.9% effluent. The No Observed Effect Concentrations for survival (over 43 days) were calculated in consecutive years as 0.1% and 1% effluent. Survival is considered a useful tool for determining toxicity endpoints using B. stenochorias. Limpet growth remained linear in effluent, with an apparent stimulation of growth at the 3-10% effluent concentration, confusing the toxicity and variability assessments. The possible addition of nutrients from the effluent points to either a potential inadequacy of the food quality provided in the chronic assessment, or the presence in the effluent of growth stimulants. Growth was also found to be too variable to allow adequate statistical conclusions about the toxicity of the effluent, although it is suggested that growth may be useful in the assessment of single compounds. Despite large individual variability in fecundity, statistical differences were discernible between effluent concentrations. The application of fecundity of B. stenochorias in hazard assessment therefore warrants further investigation. It was concluded that an assessment of textile whole effluent toxicity to B. stenochorias over an entire life cycle, and an F1 generation, is unnecessary. The development of the bucket/plastic bag method for both acute and chronic toxicity assessment of B. stenochorias was useful. In the final assessment of the usefulness of B. stenochorias as a toxicity indicator, toxicity endpoints were compared with those of the standard laboratory organism Daphnia pulex. Both in acute and chronic toxicity, B. stenochorias was found to be more sensitive. B. stenochorias is therefore considered valuable as a South African freshwater molluscan ecotoxicological indicator, with a place in hazard assessment, although further development and research is necessary before the limpet can be effectively used

Over-expression of UDP-glucose pyrophosphorylase in hybrid poplar affects carbon allocation

The effects of the over-expression of the Acetobacter xylinum UDP-glucose pyrophosphorylase (UGPase) under the control of the tandem repeat Cauliflower Mosaic Virus promoter (2335S) on plant metabolism and growth were investigated in hybrid poplar (Populus alba3grandidentata). Transcript levels, enzyme activity, growth parameters, leaf morphology, structural and soluble carbohydrates, and soluble metabolite levels were quantified in both transgenic and wild-type trees. Transgenic 2335S::UGPase poplar showed impaired growth rates, displaying reduced height growth and stem diameter. Morphologically, 2335S::UGPase trees had elongated axial shoots, and leaves that were substantially smaller in size when compared with wild-type trees at equivalent developmental stages. Biochemical analysis revealed significant increases in soluble sugar, starch, and cellulose contents, and concurrent decreases in lignin content. Lignin monomer composition was altered in favour of syringyl moieties. Detailed soluble metabolite analysis revealed that 2335S::UGPase trees had as much as a 270-fold increase in the salicylic acid 2-O-b-Dglucoside (SAG), a compound typically associated with the stress response. These data suggest that while it is possible to alter the allocation of carbon in favour of cellulose biosynthesis, whole plant changes result in unexpected decreases in growth and an increase in defence metabolites

Sugarcane transgenics expressing MYB transcription factors show improved glucose release

Additional file 1: Figure S1. Nucleotide and amino acid alignments of MYB31 and MYB42. Alignments of published (Fornalé et al. 2006) and cloned nucleotide and amino acid sequences (ORF and UTR) for ZmMYB31 (NM_001112479) and ZmMYB42 (NM_001112539). Alignments were made using the Kyoto University Bioinformatics Center website ( http://www.genome.jp/tools-bin/clustalw ) and amino acid translations were made using the ORF region of each MYB nucleotide sequences and Vector NTI software. The start and stop codons are underlined in nucleotide sequence alignments with the 5′ and 3′ UTR regions being upstream and downstream of the start and stop codons respectively. The R2 and R3 motifs in each sequence are underlined with light gray and dark grey shading respectively

Correlates of Complete Childhood Vaccination in East African Countries.

Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and country-specific barriers to complete childhood vaccination. Using data from the Demographic and Health Surveys (DHS) for Burundi, Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, we looked at the prevalence of complete vaccination for polio, measles, Bacillus Calmette-Guérin (BCG) and DTwPHibHep (DTP) as recommended by the WHO among children ages 12 to 23 months. We conducted multivariable logistic regression within each country to estimate associations between complete vaccination status and health care access and sociodemographic variables using backwards stepwise regression. Vaccination varied significantly by country. In all countries, the majority of children received at least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and Uganda less than 50% of children received a complete schedule of recommended vaccines. Being delivered in a public or private institution compared with being delivered at home was associated with increased odds of complete vaccination status. Sociodemographic covariates were not consistently associated with complete vaccination status across countries. Although no consistent set of predictors accounted for complete vaccination status, we observed differences based on region and the location of delivery. These differences point to the need to examine the historical, political, and economic context of each country in order to maximize vaccination coverage. Vaccination against these childhood diseases is a critical step towards reaching the Millennium Development Goal of reducing under-five mortality by two-thirds by 2015 and thus should be a global priority

Peptidylarginine Deiminase 3 (PAD3) Is Upregulated by Prolactin Stimulation of CID-9 Cells and Expressed in the Lactating Mouse Mammary Gland

Peptidylarginine deiminases (PADs) post-translationally convert arginine into neutral citrulline residues. Our past work shows that PADs are expressed in the canine and murine mammary glands; however, the mechanisms regulating PAD expression and the function of citrullination in the normal mammary gland are unclear. Therefore, the first objective herein was to investigate regulation of PAD expression in mammary epithelial cells. We first examined PAD levels in CID-9 cells, which were derived from the mammary gland of mid-pregnant mice. PAD3 expression is significantly higher than all other PAD isoforms and mediates protein citrullination in CID-9 cells. We next hypothesized that prolactin regulates PAD3 expression. To test this, CID-9 cells were stimulated with 5 mug/mL of prolactin for 48 hours which significantly increases PAD3 mRNA and protein expression. Use of a JAK2 inhibitor and a dominant negative (DN)-STAT5 adenovirus indicate that prolactin stimulation of PAD3 expression is mediated by the JAK2/STAT5 signaling pathway in CID-9 cells. In addition, the human PAD3 gene promoter is prolactin responsive in CID-9 cells. Our second objective was to investigate the expression and activity of PAD3 in the lactating mouse mammary gland. PAD3 expression in the mammary gland is highest on lactation day 9 and coincident with citrullinated proteins such as histones. Use of the PAD3 specific inhibitor, Cl4-amidine, indicates that PAD3, in part, can citrullinate proteins in L9 mammary glands. Collectively, our results show that upregulation of PAD3 is mediated by prolactin induction of the JAK2/STAT5 signaling pathway, and that PAD3 appears to citrullinate proteins during lactation

Personal values, social capital, and higher education student career decidedness: a new 'protean'-informed model

This study investigates the role of personal values as motivational antecedents for understanding HE student career decidedness among university business school (UBS) students. We propose a new ‘protean’ informed HE student career decidedness model for theorizing how both personal values and social capital mediators (student social capital; personal, social and enterprise skills; access to resources) help in the student-centric and self-directed processes of career decision-making. A mixed methods study combines a (stage 1) survey of 308 UBS students from five (UK) university business schools, with results from (stage 2) four student focus groups, and (stage 3) two staff-student interactive seminars. From an employability perspective, arguably, the ultimate responsibility for becoming a ‘protean graduate’ rests with each UBS student, whilst the obligation of HE staff is to effectively facilitate and nurture all possible personal growth and skills development opportunities

Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments.

BACKGROUND: The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within approximately 24-48 h of their test result. METHODS: A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (approximately within 24-48 h of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology. RESULTS: Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1013 recruits to PRINCIPLE at the start of October 2020 to 2802 recruits by 20 December 2020. Whilst procedural caveats were identified by the public consultation, out of 2639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached. CONCLUSIONS: This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions. TRIAL REGISTRATION: PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 . 26/03/2020 ISRCTN registry: ISRCTN86534580 . 20/03/2020 REC number: 20/SC/058 IRAS number: 281958

Age-dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q \u3c 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans