The Influence of Mesoscopic Surface Structure on the Electrocatalytic Selectivity of CO2 Reduction with UHV-Prepared Cu(111) Single Crystals.

The key role of morphological defects (e.g., irregular steps and dislocations) on the selectivity of model Cu catalysts for the electrocatalytic reduction of CO2 (CO2RR) is illustrated here. Cu(111) single-crystal surfaces prepared under ultrahigh vacuum (UHV) conditions and presenting similar chemical and local microscopic surface features were found to display different product selectivity during the CO2RR. In particular, changes in selectivity from hydrogen-dominant to hydrocarbon-dominant product distributions were observed based on the number of CO2RR electrolysis pretreatment cycles performed prior to a subsequent UHV surface regeneration treatment, which lead to surfaces with seemingly identical chemical composition and local crystallographic structure. However, significant mesostructural changes were observed through a micron-scale microscopic analysis, including a higher density of irregular steps on the samples producing hydrocarbons. Thus, our findings highlight that step edges are key for C-C coupling in the CO2RR and that not only atomistic but also mesoscale characterization of electrocatalytic materials is needed in order to comprehend complex selectivity trends.

Development of a single crystal sample holder for interfacing ultrahigh vacuum and electrochemical experimentation.

Electrocatalyst surfaces prepared under ultrahigh vacuum (UHV) conditions can create model surfaces to better connect theoretical calculations with experimental studies. The development of a single crystal sample holder and inert electrochemical cells prepared with modularity and chemical stability in mind would allow for expensive single crystals to be reused indefinitely in both UHV and electrochemical settings. This sample holder shows reproducible surface preparations for single crystal samples and consistent electrochemical experiments without the introduction of impurities into the surface. The presented setup has been used as a critical piece for the characterization of Cu(111) surfaces under CO2 electrochemical reduction reaction conditions as a test case.

Identifying Structure-Selectivity Correlations in the Electrochemical Reduction of CO2 : A Comparison of Well-Ordered Atomically Clean and Chemically Etched Copper Single-Crystal Surfaces.

The identification of the active sites for the electrochemical reduction of CO2 (CO2 RR) to specific chemical products is elusive, owing in part to insufficient data gathered on clean and atomically well-ordered electrode surfaces. Here, ultrahigh vacuum based preparation methods and surface science characterization techniques are used with gas chromatography to demonstrate that subtle changes in the preparation of well-oriented Cu(100) and Cu(111) single-crystal surfaces drastically affect their CO2 RR selectivity. Copper single crystals with clean, flat, and atomically ordered surfaces are predicted to yield hydrocarbons; however, these were found experimentally to favor the production of H2 . Only when roughness and defects are introduced, for example by electrochemical etching or a plasma treatment, are significant amounts of hydrocarbons generated. These results show that structural and morphological effects are the key factors determining the catalytic selectivity of CO2 RR.

A Metabolic Roadmap for Somatic Stem Cell Fate.

While metabolism was initially thought to play a passive role in cell biology by generating ATP to meet bioenergetic demands, recent studies have identified critical roles for metabolism in the generation of new biomass and provision of obligate substrates for the epigenetic modification of histones and DNA. This review details how metabolites generated through glycolysis and the tricarboxylic acid cycle are utilized by somatic stem cells to support cell proliferation and lineage commitment. Importantly, we also discuss the evolving hypothesis that histones can act as an energy reservoir during times of energy stress. Finally, we discuss how cells integrate both extrinsic metabolic cues and intrinsic metabolic machinery to regulate cell fate.

Tau positron emission tomography imaging in C9orf72 repeat expansion carriers.

BACKGROUND AND PURPOSE: AV-1451 (18 F-AV-1451, flortaucipir) positron emission tomography was performed in C9orf72 expansion carriers to assess tau accumulation and disease manifestation. METHODS: Nine clinically characterized C9orf72 expansion carriers and 18 age- and gender- matched cognitively normal individuals were psychometrically evaluated and underwent tau positron emission tomography imaging. The regional AV-1451 standard uptake value ratios from multiple brain regions were analyzed. Spearman correlation was performed to relate the AV-1451 standard uptake value ratio to clinical, psychometric and cerebrospinal fluid measures. RESULTS: C9orf72 expansion carriers had increased AV-1451 binding in the entorhinal cortex compared to controls. Primary age-related tauopathy was observed postmortem in one patient. AV-1451 uptake did not correlate with clinical severity, disease duration, psychometric performance or cerebrospinal fluid markers. CONCLUSION: C9orf72 expansion carriers exhibited increased AV-1451 uptake in entorhinal cortex compared to cognitively normal controls, suggesting a propensity for primary age-related tauopathy. However, AV-1451 accumulation was not associated with psychometric performance in our cohort.

Measuring Mitochondrial Substrate Utilization in Skeletal Muscle Stem Cells.

Skeletal muscle stem cells (MuSCs) derived from the somatic mesoderm play a critical role in successful muscle regeneration following injury and trauma. MuSCs have been found to undergo rapid changes in metabolism following a change in cell state, such as that which occurs during the transition from quiescence to an actively proliferating state. There is mounting evidence that metabolism is critically important in the regulation of quiescence, activation, and differentiation and thus the development of new techniques that aim to further probe the metabolism of MuSCs is essential. The Seahorse XF Bioanalyzer is a powerful tool that simultaneously measures the extracellular rate of change in oxygen partial pressure and pH, providing a method to measure mitochondrial respiration and lactate production. In this chapter, we describe the use of key metabolic inhibitors that allow for the investigation of mitochondrial substrate utilization in primary MuSCs.

[The care of skin lesions caused by extravasation of intravenous fluids in peripheral venous perfusion]. / Prise en charge thérapeutique des lésions cutanées après extravasation de solutés en perfusion veineuse périphérique.

INTRODUCTION: Infiltration and extravasation account for 23-78 % of the complications stemming from peripheral venous perfusions in neonatal intensive care units. Their consequences, sometimes dramatic, can be pain, infections, or even loss of skin, which can lead to nerve and/or muscle damage, particularly severe for preterm neonates. Today there are no recommendations on the care of these lesions, which can lead to an erroneous choice or to a delay in the possible treatments. OBJECTIVE: This review of the literature aims to explore and propose elements of therapeutic care collected in the scientific literature. It focuses on skin lesions due to extravasation of peripheral venous perfusions in neonatal intensive care units. METHODS: The PubMed database and the publishers' platform ScienceDirect were used. The bibliographies of the selected articles were also run. All types of studies examining one or several treatments for the care of postextravasation skin lesions in neonatal intensive care units were included in the search, without any limit on the date, except for case reports. To estimate the quality of the studies, the tool proposed by the French National Authority for Health, which classifies the various types of studies according to their proof level, was used. RESULTS/DISCUSSION: Thirteen publications were analyzed, including four case series, five retrospective studies, and four interventional studies. The vast majority of these studies have been published since 2005. No comparative, controlled, and randomized trials appear in the literature. Chronologically, we observed a growing interest in the premature infant population, in parallel with the increasing number of publications. Among the significant number of treatments proposed, five main categories were identified: topical treatment, surgery, the Gault method, no specific treatment, and others. All the skin lesions of the babies studied healed, without important aftereffects. These publications also show that most of the time a combination of different types of treatment is used depending on the lesions' progress and doctor's assessment. Few differences are made between term neonates and premature neonates in the choice of treatment. All these types of care can be applied to both populations. In spite of the lack of consensus on the care to be adopted, all the authors emphasize the important role of prevention according to the official regulations. CONCLUSION: The total absence of studies with a sufficient level of proof does not allow, at this time, the elaboration of guidelines for the care of these lesions. However, the proposals made in the literature seem promising. Therefore, it would be wise to conduct randomized trials on relatively large samples to compare these various types of treatment.

Andrée Gruslin award lecture: Metabolomics as an important modality to better understand preeclampsia.

Preeclampsia (PE) is a complex disorder that affects 3-5% of all pregnancies and is a leading cause of maternal and fetal morbidity and mortality. To date, the heterogeneity of clinical presentation, disease severity and outcomes have limited significant advances in early prediction, diagnosis, and therapeutic intervention of PE. The rapidly expanding field of metabolomics, which has the capacity to quantitatively detect low molecular weight compounds (metabolites) in tissue and biological fluids, shows tremendous promise in gaining a better understanding of PE. This review will discuss this emerging field and its contribution to recent advances in the understanding of PE pathophysiology, and identification of early predictive metabolic biomarkers for this complex disorder.

Blood pressure variability: cardiovascular risk integrator or independent risk factor?

Blood pressure (BP) variability is associated with several cardiovascular (CV) risk factors. Is BP variability measurement of any additive value, in terms of CV risk assessment strategies? To answer this question, we analyzed data from the SU.FOL.OM3 secondary prevention trial that included 2501 patients with background of CV disease history (coronary or cerebrovascular disease). BP was measured every year allowing calculation of variability of BP, expressed as s.d. and coefficient of variability (s.d./mean systolic BP) in 2157 patients. We found that systolic BP variability was associated with several CV risk factors: principally hypertension, age, and diabetes. Furthermore, all antihypertensives were positively associated with variability. Logistic regression analysis revealed that three factors were independent predictors of major CV event: coefficient of variability of systolic BP (OR=1.23 per s.d., 95% CI: 1.04-1.46, P=0.016), current smoking (OR=1.94, 95% CI: 1.03-3.66, P=0.039), and inclusion for cerebrovascular disease (OR=1.92, 95% CI: 1.29-2.87, P=0.001). Finally, when comparing logistic regression models characteristics without, and then with, inclusion of BP variability, there was a modest but statistically significant improvement (P=0.04). In conclusion, age, BP and diabetes were the major determinants of BP variability. Furthermore, BP variability has an independent prognostic value in the prediction of major CV events; but improvement in the prediction model was quite modest. This last finding is more in favor of BP variability acting as an integrator of CV risk than acting as a robust independent CV risk factor in this high-risk population.

A metabolic link to skeletal muscle wasting and regeneration.

Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed "metabolic reprogramming."

[HIV seroprevalence among STD patients in Nouakchott and Nouadhibou (Mauritania)]. / Séroprévalence VIH chez les consultants IST à Nouakchott et à Nouadhibou (Mauritanie).

This work presents the results of the behavioural and serologic survey on HIV/AIDS conducted from December 2007 to December 2008 among the group of STD (sexually transmitted disease) patients, supposed to be at HIV infection risk. In Mauritania, the last survey of HIV seroprevalence among the STD patients goes up to the year 1995 (the prevalence was estimated then to be 0.9%). The goal was to determine the seroprevalence of HIV and syphilis and to gather information on the knowledge, the sexual behaviours on a risk concerning the HIV/AIDS, and the sexually transmitted disease among these patients. The census has been made on over 224 STD patients during the period of the study, without predominance of sex and with a majority of young adults. The prevalence for HIV is 9% and for the syphilis it is 10%. Actually, the condom is widely underused by this group, even in occasional intercourse. The STD patients are a group of risk towards HIV, because of their risk behaviours and low level of knowledge.

Improving immunization coverage through budgeted microplans and sub-national performance agreements: early experience from Cambodia.

In recent years, Cambodia has demonstrated significant success in specific aspects of immunization with gains through campaign efforts in measles control and polio eradication. In contrast, routine immunization rates have failed to improve over the last five years. In response, the National Immunization Program of the Ministry of Health developed a coverage improvement planning (CIP) process. This paper describes the CIP process in Cambodia, including identified barriers to and strategies for improving coverage. Immunization coverage rose in 8 of 10 pilot districts in the year following the introduction of CIP in 2003. The mean increase in DPT3 coverage across pilot districts on an annual basis was 16%, which provides encouraging early evidence for the effectiveness of the intervention. Factors associated with success in coverage improvement included: (1) development of a needs-based micro-plan, (2) application of performance-based contracting between levels of management, (3) investment in social mobilization, (4) securing finance for health outreach programs and (5) strengthened monitoring systems. Lessons learned will guide program expansion to improve immunization coverage nationally.

Early short-term infant food supplementation, maternal weight loss and duration of breast-feeding: a randomised controlled trial in rural Senegal.

OBJECTIVE: Early supplementation of breastfed infants may have consequences both for the mother and the child. We hypothesised that it would result in decreased maternal weight loss and in shorter durations of breastfeeding and birth intervals. DESIGN: Controlled randomised population-based trial. SETTING: Six villages in the Sine area of Senegal, West Africa. SUBJECTS: Healthy breastfed infants and their mothers, 68 controls and 66 supplemented infants at randomization. INTERVENTION: Supplementation with high-energy, nutrient dense food from 4 to 7 months of age, twice daily under supervision of field workers. Both controls and supplemented infants were free to eat other complementary foods. Maternal weight was measured monthly. Dates of breastfeeding cessation and of subsequent births were collected prospectively through weekly demographic surveillance, and were analysed using Cox's regression models and 'intent-to-supplement' approach. RESULTS: Mean maternal weight gain from 4 to 7 months postpartum tended to be greater in the supplemented group (+0.25 kg/months, 95% confidence interval (CI): -0.07, +0.57). Supplemented infants were breastfed for significantly longer durations than controls (medians: 24.9 and 23.7 months, respectively, P: 0.034). Their adjusted hazard ratio (HR) for breastfeeding cessation was 0.59 (95% CI: 0.40, 0.89). Their mothers had a lower risk of a new birth than mothers of controls (adjusted HR: 0.57, 95% CI: 0.36, 0.92). CONCLUSIONS: Early short-term infant supplementation tended to decrease maternal postpartum weight loss, but it increased, rather than shortened, the duration of breastfeeding and birth interval. SPONSORSHIP: This study was supported by a grant from the French Ministry of Research (Grant 92L0623).

Change in body water distribution index in infants who become stunted between 4 and 18 months of age.

OBJECTIVE: To evaluate body composition changes using bioelectrical impedance analysis and skinfold thickness measurements in infants from tropical areas who become stunted between 4-18 months of age. DESIGN AND MEASUREMENTS: Follow-up study. Extracellular water to total body water ratio index (length(2)/resistance at low to high frequency), peripheral fat (tricipital and subscapular skinfold thickness), and length-for-age index were studied at 4 and 18 months of age. SETTINGS: Low-income areas in four tropical regions (Congo, Senegal, Bolivia and New Caledonia). SUBJECTS: Infants were included in the analysis provided they were neither stunted nor wasted at 4 months. Two groups of infants were compared, those that were stunted at 18 months (n=61) or not (n=170). RESULTS: The extracellular water to total body water ratio index and the sum of skinfold thickness measurements were similar in the two groups at 4 months, and only the extracellular water to total body water ratio index was significantly different at 18 months. When no stunting appeared between 4 and 18 months, the change in the extracellular water to total body water ratio index was not linked with variations in length-for-age, and presented the expected pattern of variation in body water compartments. When stunting occurred, variation in length-for-age was related to significant changes in the extracellular water to total body water ratio index, the biggest increase in the proportion of extracellular water being found in the most stunted infants. Variations in the sum of the two skinfold thickness measurements presented the expected pattern for the 4-18 months growth and did not differ between the two groups. CONCLUSIONS: Multifrequency resistances suggested that stunting was associated with a lack of the expansion of the intracellular compartment that is expected during normal growth of cell mass, together with preserved fat mass. SPONSORSHIPS: Supported by grant 92L0623 from the French Ministry of Research, and by Institut de Recherche pour le Développement (IRD).

Ocsyn, a novel syntaxin-interacting protein enriched in the subapical region of inner hair cells.

Sensory (hair) cells of the inner ear contain two specialized areas of membrane delivery. The first, located at the cell base, is the afferent synapse where rapid delivery of synaptic vesicles is required to convey information about auditory signals with exceedingly high temporal precision. The second area is at the apex. To accommodate the continuous movement of stereocilia and facilitate their repair, recycling of membrane components is required. Intense vesicular traffic is restricted to a narrow band of cytoplasm around the cuticular plate, which anchors stereocilia. Our previous analyses showed that SNARE proteins (syntaxin 1A/SNAP25/VAMP1) are concentrated at both poles of hair cells, consistent with their involvement in membrane delivery at both locations. To investigate further the molecules involved in membrane delivery at these two sites, we constructed a two-hybrid library of the organ of Corti and probed it with syntaxin 1A. Here we report the cloning of a novel syntaxin-binding protein that is concentrated in a previously uncharacterized organelle at the apex of inner hair cells.

Vesicle targeting in hair cells.

The mammalian hair cell has two distinct plasma membrane domains separated by tight junctions, the apical domain which contains the stereocilia and the basolateral domain which contains the presynaptic region. Little is known concerning the mechanisms that regulate vesicle trafficking to these two domains. Using SNAP 25 and syntaxin as baits, we carried out a yeast two-hybrid screen of the organ of Corti. We identified a novel syntaxin interacting protein, ocsyn, that is enriched in inner hair cells and concentrated at the apical pole. Our results are consistent with ocsyn playing a role in vesicle trafficking to the apical membrane of the hair cell.

Identification of rat EMAP, a delta-glutamate receptor binding protein.

While most subtypes of glutamate receptors have been studied extensively, less is known about the delta-glutamate receptors, delta1 and delta2. Although neither forms functional channels when expressed in heterologous cells, genetic analyses have demonstrated the physiological significance of delta2. We used the cytosolic C-terminus of the delta2 glutamate receptor subunit in a yeast two-hybrid screen of a rat brain cDNA library to identify delta-glutamate receptor binding proteins. We isolated rat EMAP, the rat homolog of a microtubule-associated protein initially isolated and characterized in echinoderms. Rat EMAP contains 10 WD-repeats, which are domains important for mediating protein-protein interactions in a wide variety of proteins. Rat EMAP binds to delta-glutamate receptor subunits within a 50-amino-acid segment of the delta C-terminus. It is widely expressed in both brain and peripheral tissues, including high expression in brainstem and enrichment in the postsynaptic density.

Melatonin protects SHSY5Y neuroblastoma cells from cobalt-induced oxidative stress, neurotoxicity and increased beta-amyloid secretion.

Heavy metals are increasingly being implicated as causative agents in neurodegenerative diseases such as Alzheimer's disease (AD). Cobalt, a positively charged transition metal, has previously been shown to be in elevated levels in the brain of AD patients compared with age-matched controls. In this study, we investigate the effects of cobalt as an inducer of oxidative stress/cell cytotoxicity and the resultant metabolic implications for neural cells. We show that cobalt is able to induce cell cytotoxicity (reduced MTT metabolism) and oxidative stress (reduced cellular glutathione). The pre-treatment of cells with the pineal indoleamine melatonin, prevented cell cytotoxicity and the induction of oxidative stress. Cobalt treatment of SHSY5Y cells increased the release of beta-amyloid (Abeta) compared with untreated controls (ratio Abeta 40/42). Melatonin pre-treatment reversed the deleterious effects of cobalt. These findings are significant as cobalt is an essential nutritional requirement, usually bound to cobalamin (vitamin B12), for all animals which in the unbound form could lead to neurotoxicity.

Molecular determinants of NMDA receptor internalization.

Although synaptic AMPA receptors have been shown to rapidly internalize, synaptic NMDA receptors are reported to be static. It is not certain whether NMDA receptor stability at synaptic sites is an inherent property of the receptor, or is due to stabilization by scaffolding proteins. In this study, we demonstrate that NMDA receptors are internalized in both heterologous cells and neurons, and we define an internalization motif, YEKL, on the distal C-terminus of NR2B. In addition, we show that the synaptic protein PSD-95 inhibits NR2B-mediated internalization, and that deletion of the PDZ-binding domain of NR2B increases internalization in neurons. This suggests an involvement for PSD-95 in NMDA receptor regulation and an explanation for NMDA receptor stability at synaptic sites.