Natural volcanic CO2 seeps reveal future trajectories for host–microbial associations in corals and sponges

Atmospheric carbon dioxide (CO₂) levels are rapidly rising causing an increase in the partial pressure of CO₂ (pCO₂) in the ocean and a reduction in pH known as ocean acidification (OA). Natural volcanic seeps in Papua New Guinea expel 99% pure CO₂ and thereby offer a unique opportunity to explore the effects of OA in situ. The corals Acropora millepora and Porites cylindrica were less abundant and hosted significantly different microbial communities at the CO₂ seep than at nearby control sites <500 m away. A primary driver of microbial differences in A. millepora was a 50% reduction of symbiotic Endozoicomonas. This loss of symbiotic taxa from corals at the CO₂ seep highlights a potential hurdle for corals to overcome if they are to adapt to and survive OA. In contrast, the two sponges Coelocarteria singaporensis and Cinachyra sp. were ∼40-fold more abundant at the seep and hosted a significantly higher relative abundance of Synechococcus than sponges at control sites. The increase in photosynthetic microbes at the seep potentially provides these species with a nutritional benefit and enhanced scope for growth under future climate scenarios (thus, flexibility in symbiosis may lead to a larger niche breadth). The microbial community in the apparently pCO₂-sensitive sponge species S. massa was not significantly different between sites. These data show that responses to elevated pCO₂ are species-specific and that the stability and flexibility of microbial partnerships may have an important role in shaping and contributing to the fitness and success of some hosts.     

Spatio-Temporal Variations in Malaria Incidence in Children Less than 10 Years Old,Health District of Sokone,Senegal, 2010–2013

Introduction

Malaria is a leading cause of morbidity and mortality in sub-Saharan Africa. Detailed characterization of the risks for malaria, among populations living in areas where the disease is endemic, is an important priority, especially for planning and evaluating future malaria-control tools. A prospective cohort study was implemented in children under ten years living in rural areas with high Plasmodium falciparum transmission in Senegal.

Methods

Malaria incidence was prospectively evaluated over three year follow-up among a cohort of children aged less than 10 years old living in eight villages of the Sokone health district. The parents of 1316 children comprising a passive case detection cohort were encouraged to seek care from the study health centers at any time their child felt sick. In the event of reported history of fever within 24 hours or measured axillary temperature ≥ 37.5°C, a Rapid Diagnostic Test (RDT) was performed.

Results

From November 2010 to October 2013, among the 1468 reported febrile episodes, 264 were confirmed malaria episodes. Over the 3 years, 218 (16.9%) children experienced at least one clinical malaria episode. Cumulative malaria incidence was 7.3 episodes per 100 children-year at risk, with remarkably heterogeneous rates from 2.5 to 10.5 episodes per 100 children-year at risk. Clinical malaria prevalence ranged from 11.5 to 28.4% in the high transmission season versus from 9.6 to 21.2% in the low transmission season.

Conclusion

This longitudinal community-based study shows that occurrence of clinical malaria was not evenly distributed among all the cohort children in the eight villages. It demonstrates the complexity of spatial distribution of malaria incidence at a local level, even in a region of vegetation and altitudinal homogeneity.     

Valuing and Sustaining (or Not) the Ability of Volunteer Community Health Workers to Deliver Integrated Community Case Management in Northern Ghana: A Qualitative Study

Background

Within the integrated community case management of childhood illnesses (iCCM) programme, the traditional health promotion and prevention role of community health workers (CHWs) has been expanded to treatment. Understanding both the impact and the implementation experience of this expanded role are important. In evaluating UNICEF’s implementation of iCCM, this qualitative case study explores the implementation experience in Ghana.

Methods and Findings

Data were collected through a rapid appraisal using focus groups and individual interviews during a field visit in May 2013 to Accra and the Northern Region of Ghana. We sought to understand the experience of iCCM from the perspective of locally based UNICEF staff, their partners, researchers, Ghana health services management staff, CHWs and their supervisors, nurses in health facilities and mothers receiving the service. Our analysis of the findings showed that there is an appreciation both by mothers and by facility level staff for the contribution of CHWs. Appreciation was expressed for the localisation of the treatment of childhood illness, thus saving mothers from the effort and expense of having to seek treatment outside of the village. Despite an overall expression of value for the expanded role of CHWs, we also found that there were problems in supporting and sustaining their efforts. The data showed concern around CHWs being unpaid, poorly supervised, regularly out of stock, lacking in essential equipment and remaining outside the formal health system.

Conclusions

Expanding the roles of CHWs is important and can be valuable, but contextual and health system factors threaten the sustainability of iCCM in Ghana. In this and other implementation sites, policymakers and key donors need to take into account historical lessons from the CHW literature, while exploring innovative and sustainable mechanisms to secure the programme as part of a government owned and government led strategy.     

Early-Onset Atopic Dermatitis in Children: Which Are the Phenotypes at Risk of Asthma? Results from the ORCA Cohort

Background

Atopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term “atopic march”. However, this classic sequence is not always present and only a few studies have addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma.

Methods

We performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6.

Results

We identified 3 clusters - cluster 1 (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called “AD with low sensitization”; - cluster 2 (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called “AD with multiple sensitizations” - cluster 3 (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called “AD with familial history of asthma”. Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p<0.01).

Conclusion

Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma.     

Safety of adjuvant intensity-modulated postoperative radiation therapy in endometrial cancer: Clinical data and dosimetric parameters according to the International Commission on Radiation Units (ICRU) 83 report

AimTo report a single-institution experience using postoperative pelvic Intensity Modulation Radiation Therapy (IMRT) using tomotherapy accelerators (TA) in postoperative endometrial cancer (EC) regarding ICRU 83 recommendations.BackgroundIMRT in gynecological malignancies provides excellent dosimetric data, lower rates of adverse events and clinical data similar to historical series.Material and methodsSeventy-six patients with EC were postoperatively treated with adjuvant IMRT using TA. The IMRT dose was 45 Gy for patients without positive lymph nodes and Type I histology and 50.4 Gy for patients with positive lymph nodes and/or type II histology.ResultsWith a median follow-up of 29 months, the 12- and 24-month Overall Survival (OS) and Disease-Free Survival (DFS) were 96%, 93%, 87%, and 74%, respectively. Age of less than 60 years was associated with better OS (HR: 8.9; CI: 1.1–68) and DFS (HR: 3.5; CI: 1.2–10.2). Patients with Type II and Type I Grade III histology had a worse OS (HR: 3.3; CI: 1.1–11). Five women (6.6%) presented in-field local vaginal recurrence, 2 (2.6%) presented non-in-field vaginal recurrence, 4 (5.2%) presented pelvic node and distant recurrence and 11 (14.4%) presented only distant metastases. One patient stopped radiation treatment due to Grade III acute diarrhea. No Grade III late toxicity was observed. Planning Target Volume (PTV) coverage showed mean D2, D50, D95, and D98 of 51.64–46.23 Gy, 49.49–44.97 Gy, 48.62–43.96 Gy, and 48.47–43.58 Gy for patients who received 45 and 50.4 Gy, respectively.ConclusionsIMRT with TA in postoperative EC shows excellent conformity and homogeneity of PTV dose. Without Grade III late toxicity, data from this cohort demonstrated the utility of IMRT.     

Tctex1d2 associates with short-rib polydactyly syndrome proteins and is required for ciliogenesis

Short-rib polydactyly syndromes (SRPS) arise from mutations in genes involved in retrograde intraflagellar transport (IFT) and basal body homeostasis, which are critical for cilia assembly and function. Recently, mutations in WDR34 or WDR60 (candidate dynein intermediate chains) were identified in SRPS. We have identified and characterized Tctex1d2, which associates with Wdr34, Wdr60 and other dynein complex 1 and 2 subunits. Tctex1d2 and Wdr60 localize to the base of the cilium and their depletion causes defects in ciliogenesis. We propose that Tctex1d2 is a novel dynein light chain important for trafficking to the cilium and potentially retrograde IFT and is a new molecular link to understanding SRPS pathology.     

Netamines O–S,Five New Tricyclic Guanidine Alkaloids from the Madagascar Sponge Biemna laboutei,and Their Antimalarial Activities

In our continuing program to isolate new compounds from the Madagascar sponge Biemna laboutei, five new tricyclic guanidine alkaloids, netamines O – S ( 1 – 5 , resp.), have been identified together with the known compounds netamine E ( 6 ) and mirabilin J ( 7 ). The structures of all new netamines were assigned on the basis of spectroscopic analyses. Their relative configurations were established by analysis of ROESY data and comparison with literature data. Netamines O, P, and Q, which were isolated in sufficient quantities, were tested for their cytotoxic activities against KB cells and their activities against the malaria parasite Plasmodium falciparum. Netamines O and Q were found to be moderately cytotoxic. Netamines O, P, and Q exhibited antiplasmodial activities with IC₅₀ values of 16.99±4.12, 32.62±3.44, and 8.37±1.35 μM , respectively.     

Metabolic Outcome of Female Mice Exposed to a Mixture of Low-Dose Pollutants in a Diet-Induced Obesity Model

Pollutants are suspected to contribute to the etiology of obesity and related metabolic disorders. Apart from occupational exposure which concerns a subset of chemicals, humans are mostly exposed to a large variety of chemicals, all life-long and at low doses. Food ingestion is a major route of exposure and it is suggested that pollutants have a worsened impact when combined with a high-fat diet. In the experimental studies described herein, we aimed to add further evidence on the metabolic impact of food pollutants using a recently set up model in which mice are life-long fed a high-fat/high-sucrose diet (HFSD) with/without common food pollutants shown to exhibit metabolic disrupting activities. Specifically, this mixture comprised bisphenol A, dioxin, polychlorobiphenyl PCB153, and phthalate and was added in HFSD at doses resulting in mice exposure at the Tolerable Daily Intake dose range for each pollutant. We herein focused on the 7-week-old females which exhibited early signs of obesity upon HFSD feeding. We observed no signs of toxicity and no additional weight gain following exposure to the mixture but alleviated HFSD-induced glucose intolerance in the absence of alteration of gluconeogenesis and steatosis. It suggested that the observed metabolic improvement was more likely due to effects on muscle and/or adipose tissues rather than on the liver. Consistently, female mice exhibited enhanced lean/fat mass ratio and skeletal muscle insulin sensitivity. Moreover, expression levels of inflammatory markers were reduced in adipose tissue at 7 but enhanced at 12 weeks of age in agreement with the inverse alterations of glucose tolerance observed at these ages upon pollutant exposure in the HFSD-fed females. Collectively, these data suggest apparent biphasic effects of pollutants upon HFSD feeding along with obesity development. These effects were not observed in males and may depend on interactions between diet and pollutants.     

An essential role for talin during alpha(M)beta(2)-mediated phagocytosis

The cytoskeletal, actin-binding protein talin has been previously implicated in phagocytosis in Dictyostelium discoideum and mammalian phagocytes. However, its mechanism of action during internalization is not understood. Our data confirm that endogenous talin can occasionally be found at phagosomes forming around IgG- and C3bi-opsonized red blood cells in macrophages. Remarkably, talin knockdown specifically abrogates uptake through complement receptor 3 (CR3, CD11b/CD18, alpha(M)beta(2) integrin) and not through the Fc gamma receptor. We show that talin physically interacts with CR3/alpha(M)beta(2) and that this interaction involves the talin head domain and residues W747 and F754 in the beta(2) integrin cytoplasmic domain. The CR3/alpha(M)beta(2)-talin head interaction controls not only talin recruitment to forming phagosomes but also CR3/alpha(M)beta(2) binding activity, both in macrophages and transfected fibroblasts. However, the talin head domain alone cannot support phagocytosis. Our results establish for the first time at least two distinct roles for talin during CR3/alpha(M)beta(2)-mediated phagocytosis, most noticeably activation of the CR3/alpha(M)beta(2) receptor and phagocytic uptake.     

HMM-Kalign: a tool for generating sub-optimal HMM alignments

Recent development of strategies using multiple sequence alignments (MSA) or profiles to detect remote homologies between proteins has led to a significant increase in the number of proteins whose structures can be generated by comparative modeling methods. However, prediction of the optimal alignment between these highly divergent homologous proteins remains a difficult issue. We present a tool based on a generalized Viterbi algorithm that generates optimal and sub-optimal alignments between a sequence and a Hidden Markov Model. The tool is implemented as a new function within the HMMER package called hmmkalign.