Dynamical Behavior of an Eco-epidemiological Model Incorporating Prey Refuge and Prey Harvesting

In this paper an eco-epidemiological model incorporating a prey refuge and prey harvesting with disease in the prey-population is considered. Predators are assumed to consume both the susceptible and infected prey at different rates. The positivity and boundedness of the solution of the system are discussed. The existence and stability of the biologically feasible equilibrium points are investigated. Numerical simulations are performed to support our analytical findings

Genetic Signatures for \u3cem\u3eHelicobacter pylori\u3c/em\u3e Strains of West African Origin

Helicobacter pylori is a genetically diverse bacterial species that colonizes the stomach in about half of the human population. Most persons colonized by H. pylori remain asymptomatic, but the presence of this organism is a risk factor for gastric cancer. Multiple populations and subpopulations of H. pylori with distinct geographic distributions are recognized. Genetic differences among these populations might be a factor underlying geographic variation in gastric cancer incidence. Relatively little is known about the genomic features of African H. pylori strains compared to other populations of strains. In this study, we first analyzed the genomes of H. pylori strains from seven globally distributed populations or subpopulations and identified encoded proteins that exhibited the highest levels of sequence divergence. These included secreted proteins, an LPS glycosyltransferase, fucosyltransferases, proteins involved in molybdopterin biosynthesis, and Clp protease adaptor (ClpS). Among proteins encoded by the cag pathogenicity island, CagA and CagQ exhibited the highest levels of sequence diversity. We then identified proteins in strains of Western African origin (classified as hspWAfrica by MLST analysis) with sequences that were highly divergent compared to those in other populations of strains. These included ATP-dependent Clp protease, ClpS, and proteins of unknown function. Three of the divergent proteins sequences identified in West African strains were characterized by distinct insertions or deletions up to 8 amino acids in length. These polymorphisms in rapidly evolving proteins represent robust genetic signatures for H. pylori strains of West African origin

Lysophosphatidic acid-3 receptor-mediated feed-forward production of lysophosphatidic acid: an initiator of nerve injury-induced neuropathic pain

<p>Abstract</p> <p>Background</p> <p>We previously reported that intrathecal injection of lysophosphatidylcholine (LPC) induced neuropathic pain through activation of the lysophosphatidic acid (LPA)-1 receptor, possibly via conversion to LPA by autotaxin (ATX).</p> <p>Results</p> <p>We examined <it>in vivo </it>LPA-induced LPA production using a biological titration assay with B103 cells expressing LPA₁receptors. Intrathecal administration of LPC caused time-related production of LPA in the spinal dorsal horn and dorsal roots, but not in the dorsal root ganglion, spinal nerve or sciatic nerve. LPC-induced LPA production was markedly diminished in ATX heterozygotes, and was abolished in mice that were deficient in LPA₃, but not LPA₁or LPA₂receptors. Similar time-related and LPA₃receptor-mediated production of LPA was observed following intrathecal administration of LPA. In an <it>in vitro </it>study using spinal cord slices, LPA-induced LPA production was also mediated by ATX and the LPA₃receptor. Intrathecal administration of LPA, in contrast, induced neuropathic pain, which was abolished in mice deficient in LPA₁or LPA₃receptors.</p> <p>Conclusion</p> <p>These findings suggest that feed-forward LPA production is involved in LPA-induced neuropathic pain.</p

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Pregnancy-related interventions in mothers at risk for gestational diabetes in Asian India and low and middle-income countries (PRIMORDIAL study): protocol for a randomised controlled trial.

INTRODUCTION: Lifestyle modification is the mainstay of gestational diabetes mellitus (GDM) prevention. However, clinical trials evaluating the safety and efficacy of diet or physical activity (PA) in low-income and middle-income settings such as Africa and India are lacking. This trial aims to evaluate the efficacy of yoghurt consumption and increased PA (daily walking) in reducing GDM incidence in high-risk pregnant women. METHODS AND ANALYSIS: The study is a 2×2 factorial, open-labelled, multicentre randomised controlled trial to be conducted in Vellore, South India and The Gambia, West Africa. 'High-risk' pregnant women (n=1856) aged ≥18 years and ≤16 weeks of gestational age, with at least one risk factor for developing GDM, will be randomised to either (1) yoghurt (2) PA (3) yoghurt +PA or (4) standard antenatal care. Participants will be followed until 32 weeks of gestation with total active intervention lasting for a minimum of 16 weeks. The primary endpoint is GDM incidence at 26-28 weeks diagnosed using International Association of the Diabetes and Pregnancy Study Groups criteria or elevated fasting glucose (≥5.1 mmol/L) at 32 weeks. Secondary endpoints include absolute values of fasting plasma glucose concentration at 32 weeks gestation, maternal blood pressure, gestational weight gain, intrapartum and neonatal outcomes. Analysis will be both by intention to treat and per-protocol. Continuous outcome measurements will be analysed using multiple linear regression and binary variables by logistic regression. ETHICS AND DISSEMINATION: The study is approved by Oxford Tropical Research Ethics Committee (44-18), ethics committees of the Christian Medical College, Vellore (IRB 11367) and MRCG Scientific Coordinating Committee (SCC 1645) and The Gambia Government/MRCG joint ethics committee (L2020.E15). Findings of the study will be published in peer-reviewed scientific journals and presented in conferences. TRIAL REGISTRATION NUMBER: ISRCTN18467720

Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni

The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts

Micronutrient Deficiencies, Nutritional Status and the Determinants of Anemia in Children 0-59 Months of Age and Non-Pregnant Women of Reproductive Age in The Gambia.

Data on micronutrient deficiency prevalence, nutrition status, and risk factors of anemia in The Gambia is scanty. To fill this data gap, a nationally representative cross-sectional survey was conducted on 1354 children (0-59 months), 1703 non-pregnant women (NPW; 15-49 years), and 158 pregnant women (PW). The survey assessed the prevalence of under and overnutrition, anemia, iron deficiency (ID), iron deficiency anemia (IDA), vitamin A deficiency (VAD), and urinary iodine concentration (UIC). Multivariate analysis was used to assess risk factors of anemia. Among children, prevalence of anemia, ID, IDA, and VAD was 50.4%, 59.0%, 38.2%, and 18.3%, respectively. Nearly 40% of anemia was attributable to ID. Prevalence of stunting, underweight, wasting, and small head circumference was 15.7%, 10.6%, 5.8%, and 7.4%, respectively. Among NPW, prevalence of anemia, ID, IDA and VAD was 50.9%, 41.4%, 28.0% and 1.8%, respectively. Anemia was significantly associated with ID and vitamin A insufficiency. Median UIC in NPW and PW was 143.1 µg/L and 113.5 ug/L, respectively. Overall, 18.3% of NPW were overweight, 11.1% obese, and 15.4% underweight. Anemia is mainly caused by ID and poses a severe public health problem. To tackle both anemia and ID, programs such as fortification or supplementation should be intensified

Prevalence and co-existence of cardiometabolic risk factors and associations with nutrition-related and socioeconomic indicators in a national sample of Gambian women.

Cardiovascular diseases (CVD) are on the rise in Sub-Saharan Africa, and a large proportion of the adult population is thought to suffer from at least one cardiometabolic risk factor. This study assessed cardiometabolic risk factors and the contribution of nutrition-related indicators in Gambian women. The prevalence and co-existence of diabetes (elevated glycated hemoglobin (HbA1c ≥ 6.5%) or prediabetes (HbA1c ≥ 5.7% to  3 mg/L or alpha-1-acid glycoprotein (AGP) > 1 g/L) and the contribution of nutrition related and socioeconomic indicators were measured in non-pregnant women 15-49 years of age in the Gambia using data from a nationally representative cross-sectional stratified survey. Nationally, 54.5% (95% CI: 47.4, 61.4) of 1407 women had elevated HbA1c. Of these, 14.9% were diabetic and 85.1% were prediabetic. Moreover, 20.8% (95% CI 17.8, 20.0) of 1685 women had hypertension, 11.1% (95% CI 9.0, 13.7) of 1651 were obese and 17.2% (95% CI 5.1, 19.6) of 1401 had inflammation. At least one of the aforementioned cardiometabolic risk factor was present in 68.3% (95% CI 63.0, 73.1) of women. Obesity increased the risk of hypertension (aRR 1.84; 95% CI 1.40, 2.41), diabetes (aRR 1.91; 95% CI 1.29, 2.84), elevated HbA1c (aRR 1.31; 95% CI 1.14, 1.51) and inflammation (aRR 3.47; 95% CI 2.61, 4.61). Inflammation increased the risk of hypertension (aRR 1.42; 95% CI 1.14, 1.78). Aging increased the risk of hypertension, obesity and inflammation. Further, inadequate sanitation increased the risk for diabetes (aRR 1.65; 95% CI 1.17, 2.34) and iron deficiency increased the risk of elevated HbA1c (aRR 1.21; 95% CI 1.09, 1.33). The high prevalence of cardiometabolic risk factors and their co-existence in Gambian women is concerning. Although controlling obesity seems to be key, multifaceted strategies to tackle the risk factors separately are warranted to reduce the prevalence or minimize the risk of CVD

The dynamics of nasopharyngeal streptococcus pneumoniae carriage among rural Gambian mother-infant pairs

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>is an important cause of community acquired pneumonia, sepsis, meningitis and otitis media globally and has been incriminated as a major cause of serious childhood bacterial infections in The Gambia. Better understanding of the dynamics of transmission and carriage will inform control strategies.</p> <p>Methods</p> <p>This study was conducted among 196 mother-infant pairs recruited at birth from six villages in the West Kiang region of The Gambia. Nasopharyngeal swabs were collected from mother-infant pairs at birth (within 12 hours of delivery), 2, 5 and 12 months. Standard techniques of culture were used to identify carriage and serotype <it>S. pneumoniae</it>.</p> <p>Results</p> <p>Of 46 serotypes identified, the 6 most common, 6A, 6B, 14, 15, 19F and 23F, accounted for 67.3% of the isolates from infants. Carriage of any serotype among infants rose from 1.5% at birth to plateau at approximately 80% by 2 m (prevalence at 2 m = 77%; 5 m = 86%; 12 m = 78%). Likewise, maternal carriage almost doubled in the first 2 months post-partum and remained elevated for the next 10 m (prevalence at birth = 13%; 2 m = 24%; 5 m = 22%; 12 m = 21%). Carriage was significantly seasonal in both infants and mothers with a peak in December and lowest transmission in August. The total number of different serotypes we isolated from each infant varied and less than would be expected had the serotypes assorted independently. In contrast, this variability was much as expected among mothers. The half-life of a serotype colony was estimated to be 1.90 m (CI_95%: 1.66-2.21) in infants and 0.75 m (CI_95%: 0.55-1.19) in mothers. While the odds for a serotype to be isolated from an infant increased by 9-fold if it had also been isolated from the mother, the population attributable fraction (PAF) of pneumococcal carriage in infants due to maternal carriage was only 9.5%. Some marked differences in dynamics were observed between vaccine and non-vaccine serotypes.</p> <p>Conclusions</p> <p>Colonisation of the nasopharynx in Gambian infants by <it>S. pneumoniae </it>is rapid and highly dynamic. Immunity or inter-serotype competition may play a role in the dynamics. Reducing mother-infant transmission would have a minimal effect on infant carriage.</p

Small Heat Shock Protein αA-Crystallin Prevents Photoreceptor Degeneration in Experimental Autoimmune Uveitis

The small heat shock protein, αA-crystallin null (αA−/−) mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU). In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA−/− and wild type mice with EAU as donors and Rag2−/− as the recipient mice), which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ), both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses