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International audience; Background: ESBL-producing Escherichia coli (ESBL-Ec) is considered a key indicator for antimicrobial resistance (AMR) epidemiological surveillance in animal, human and environment compartments. There is likelihood of ESBL-Ec animal-human transmission but proof of cross-compartment transmission is still unclear.Objectives: To characterize ESBL-Ec genetic similarity in various compartments (humans, animals and environment) from a rural area of Madagascar.Methods: We collected ESBL-Ec isolates prospectively from humans, animals and the environment (water) between April and October 2018. These isolates were subject to WGS and analysed with cutting-edge phylogenomic methods to characterize population genetic structure and infer putative transmission events among compartments.Results: Of the 1454 samples collected, 512 tested positive for ESBL-Ec. We successfully sequenced 510 samples, and a phylogenomic tree based on 179 365 SNPs was produced. Phylogenetic distances between and amongst compartments were indistinguishable, and 104 clusters of recent transmission events between compartments were highlighted. Amongst a large diversity of ESBL-Ec genotypes, no lineage host specificity was observed, indicating the regular occurrence of ESBL-Ec transfer among compartments in rural Madagascar.Conclusions: Our findings stress the importance of using a phylogenomic approach on ESBL-Ec samples in various putative compartments to obtain a clear baseline of AMR transmissions in rural settings, where one wants to identify risk factors associated with transmission or to measure the effect of 'One Health' interventions in low- and middle-income countries.

Supplemental material for this article can be accessed here: https://doi.org/10.1080/14772000.2022.2130464; International audience; Determining the relative importance of dispersal and vicariance events across neotropical regions is a major goal in biogeography. These events are thought to be related to important landscape changes, notably the transition of Amazonia toward its modern hydrological configuration ca. 10 million years ago. We investigated the spatio-temporal context of the diversification of one of the major lineages of Pristimantis, a widespread and large genus of direct-developing Neotropical frogs. We gathered a spatially and taxonomically extensive sampling of mitochondrial DNA sequences from 754 Pristimantis gr. conspicillatus specimens, which led to delimiting 75 Operational Taxonomic Units (OTUs). Complete mitogenomes of 35 of these OTUs were assembled and collated with two nuDNA loci to reconstruct a time-calibrated phylogeny. We identified five major clades that diverged around the Oligocene-Miocene transition and that are largely restricted to distinct Neotropical regions i.e. Western Amazonia (P. conspicillatus clade), the Brazilian Shield (P. fenestratus clade), the Atlantic Forest (P. ramagii clade), the Guiana Shield (P. vilarsi clade) and the northern Andes (P. nicefori clade). The majority of the diversification events within these clades occurred in-situ from the early Miocene onward. Yet, a few ancient dispersal/vicariance events are inferred to have occurred among trans-Andean forests, the Atlantic Forest, the Brazilian and the Guiana Shields, but almost none in the last 10 Ma. The radical landscape transformations during the Miocene caused by the Andean orogeny and hydrological barriers such as the Pebas System and the subsequent transcontinental configuration of the Amazon drainage is a likely explanation for the isolation of the different clades within the P. gr. conspicillatus.

International audience; Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.

International audience; Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2–5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.

BackgroundAnaemia occurs in children when the haemoglobin level in the blood is less than the normal (11 g/dL), the consequence is the decrease of oxygen quantity in the tissues. It is a prevalent public health problem in many low-income countries, including Madagascar, and data on risk factors are lacking. We used existing data collected within the pathophysiology of environmental enteric dysfunction (EED) in Madagascar and the Central African Republic project (AFRIBIOTA project) conducted in underprivileged neighbourhoods of Antananarivo to investigate the factors associated with anaemia in children 24 to 59 months of age.MethodsChildren included in the AFRIBIOTA project in Antananarivo for whom data on haemoglobin and ferritin concentrations were available were included in the study. Logistic regression modelling was performed to identify factors associated with anaemia.ResultsOf the 414 children included in this data analysis, 24.4% were found to suffer from anaemia. We found that older children (adjusted OR: 0.95; 95% CI: 0.93–0.98) were less likely to have anaemia. Those with iron deficiency (adjusted OR: 6.1; 95% CI: 3.4–11.1) and those with a high level of faecal calprotectin (adjusted OR: 2.5; 95% CI: 1.4–4.4) were more likely to have anaemia than controls.ConclusionsTo reduce anaemia in the children in this underprivileged area, more emphasis should be given to national strategies that improve children’s dietary quality and micronutrient intake. Furthermore, existing measures should be broadened to include measures to reduce infectious disease burden.

Artículo con 10 figuras, We present a co-axial acoustic-based optical coherence vibrometry probe (CoA-OCV) for vibro-acoustic resonance quantification in biological tissues. Sample vibrations were stimulated via a loudspeaker, and pre-compensation was used to calibrate the acoustic spectrum. Sample vibrations were measured via phase-sensitive swept-source optical coherence tomography (OCT). Resonance frequencies of corneal phantoms were measured at varying intraocular pressures (IOP), and dependencies on Young¿s Modulus (E), phantom thickness and IOP were observed. Cycling IOP revealed hysteresis. For E = 0.3 MPa, resonance frequencies increased with IOP at a rate of 3.9, 3.7 and 3.5 Hz/mmHg for varied thicknesses and 1.7, 2.5 and 2.8 Hz/mmHg for E = 0.16 MPa. Resonance frequencies increased with thickness at a rate of 0.25 Hz/µm for E = 0.3 MPa, and 0.40 Hz/µm for E = 0.16 MPa. E showed the most predominant impact in the shift of the resonance frequencies. Full width at half maximum (FWHM) of the resonance modes increased with increasing thickness and decreased with increasing E. Only thickness and E contributed to the variance of FWHM. In rabbit corneas, resonance frequencies of 360–460 Hz were observed. The results of the current study demonstrate the feasibility of CoA-OCV for use in future OCT-V studies., The research leading to these results has received funding from: Horizon 2020 European Project Imcustomeye (H2020-ICT-2017 Ref. 779960); European Research Council 2018-ADG-SILKEYE-833106; Spanish Government FIS2017-84753-R, PID2020-115191RB-I00; NIH NIE P30EY 001319; Unrestricted Funds Research to Prevent Blindness, NY; Juan de la Cierva (IJC2018-037508-I); L'Oréal-UNESCO “For Women in Science” Spain; Fundacja na rzecz Nauki Polskiej (MAB/2019/12); Polish National Agency for Academic Exchange, (NAWA ULAM/2020/1/00176).The funding organizations had no role in the design or conduct of this research.

International audience; Stunting and environmental enteric dysfunction (EED) may be responsible for altered gut and systemic immune responses. However, their impact on circulating immune cell populations remains poorly characterized during early life. A detailed flow cytometry analysis of major systemic immune cell populations in 53 stunted and 52 non-stunted (2 to 5 years old) children living in Antananarivo (Madagascar) was performed. Compared to age-matched non-stunted controls, stunted children aged 2-3 years old had a significantly lower relative proportion of classical monocytes. No significant associations were found between stunting and the percentages of effector T helper cell populations (Th1, Th2, Th17, Th1Th17, and cTfh). However, we found that HLA-DR expression (MFI) on all memory CD4+ or CD8+ T cell subsets was significantly lower in stunted children compared to non-stunted controls. Interestingly, in stunted children compared to the same age-matched non-stunted controls, we observed statistically significant age-specific differences in regulatory T cells (Treg) subsets. Indeed, in 2- to 3-year-old stunted children, a significantly higher percentage of memory Treg, whilst a significantly lower percentage of naive Treg, was found. Our results revealed that both innate and adaptive systemic cell percentages, as well as activation status, were impacted in an age-related manner during stunting. Our study provides valuable insights into the understanding of systemic immune system changes in stunted children.

International audience; Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.

The fundamental limits currently faced by traditional computing devices necessitate the exploration of ways to store, compute, and transmit information going beyond the current CMOS-based technologies. Here, we propose a three-dimensional (3D) magnetic interconnector that exploits geometry-driven automotion of domain walls (DWs), for the transfer of magnetic information between functional magnetic planes. By combining state-of-the-art 3D nanoprinting and standard physical vapor deposition, we prototype 3D helical DW conduits. We observe the automotion of DWs by imaging their magnetic state under different field sequences using X-ray microscopy, observing a robust unidirectional motion of DWs from the bottom to the top of the spirals. From experiments and micromagnetic simulations, we determine that the large thickness gradients present in the structure are the main mechanism for 3D DW automotion. We obtain direct evidence of how this tailorable magnetic energy gradient is imprinted in the devices, and how it competes with pinning effects that are due to local changes in the energy landscape. Our work also predicts how this effect could lead to high DW velocities, reaching the Walker limit during automotion. This work demonstrates a possible mechanism for efficient transfer of magnetic information in three dimensions., This work was supported by the EPSRC Cambridge NanoDTC EP/L015978/1, the Winton Program for the Physics of Sustainability, the project CALIPSOplus (under Grant Agreement No. 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020), and by the European Community (under the Horizon 2020 Program, Contract No. 101001290, 3DNANOMAG). L.S. acknowledges support from St. Johns College of the University of Cambridge. C.D. was supported by the Leverhulme Trust (No. ECF-2018-016), the Isaac Newton Trust (No. 18-08), and the L’Oréal-UNESCO UK and Ireland Fellowship For Women In Science. A.H.-R. acknowledges support from Spanish AEI, under Project Reference No. PID2019-104604RB/AEI/10.13039/501100011033. The authors acknowledge the University of Vienna research platform MMM Mathematics–Magnetism–Materials, the FWF (Project No. I 4917), and Aragon Government through the Project Q-MAD.

Environmental Enteric Dysfunction (EED) refers to an incompletely defined syndrome of inflammation, reduced absorptive capacity, and reduced barrier function in the small intestine. It is widespread among children and adults in low- and middle-income countries and is also associated with poor sanitation and certain gut infections possibly resulting in an abnormal gut microbiota, small intestinal bacterial overgrowth (SIBO) and stunting. We investigated bacterial pathogen exposure in stunted and non-stunted children in Antananarivo, Madagascar by collecting fecal samples from 464 children (96 severely stunted, 104 moderately stunted and 264 non-stunted) and the prevalence of SIBO in 109 duodenal aspirates from stunted children (61 from severely stunted and 48 from moderately stunted children). SIBO assessed by both aerobic and anaerobic plating techniques was very high: 85.3% when selecting a threshold of ≥105 CFU/ml of bacteria in the upper intestinal aspirates. Moreover, 58.7% of the children showed more than 106 bacteria/ml in these aspirates. The most prevalent cultivated genera recovered were Streptococcus, Neisseria, Staphylococcus, Rothia, Haemophilus, Pantoea and Branhamella. Feces screening by qPCR showed a high prevalence of bacterial enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, such as Shigella spp., enterotoxigenic Escherichia coli, enteropathogenic E. coli and enteroaggregative E. coli. These pathogens were detected at a similar rate in stunted children and controls, all showing no sign of severe diarrhea the day of inclusion but both living in a highly contaminated environment (slum-dwelling). Interestingly Shigella spp. was the most prevalent enteropathogen found in this study (83.3%) without overrepresentation in stunted children.

19 pags., 9 figs., 5 tabs., Quantifying the full 3-D shape of the human crystalline lens is important for improving intraocular lens power or sizing calculations in treatments of cataract and presbyopia. In a previous work we described a novel method for the representation of the full shape of the ex vivo crystalline lens called eigenlenses, which proved more compact and accurate than compared state-of-the art methods of crystalline lens shape quantification. Here we demonstrate the use of eigenlenses to estimate the full shape of the crystalline lens in vivo from optical coherence tomography images, where only the information visible through the pupil is available. We compare the performance of eigenlenses with previous methods of full crystalline lens shape estimation, and demonstrate an improvement in repeatability, robustness and use of computational resources. We found that eigenlenses can be used to describe efficiently the crystalline lens full shape changes with accommodation and refractive error., HORIZON EUROPE European Research Council (IMCUSTOMEYE H2020-ICT-2017 Ref. 779960;); European Research Council (SILKEYE H2020-ERC-571 2018-ADG Ref.833106); Ministerio de Ciencia e Innovación (PID2020-115191RB-I00); Narodowa Agencja Wymiany Akademickiej (ULAM 2020/1/00176); Fundacja narzecz Nauki Polskiej (MAB/2019/12); L’Oréal-UNESCO “For Women in Science”; Ministerio de Ciencia, Innovación y Universidades (IJC2018-037508-I, Juan de la Cierva-Incorporation); Research to Prevent Blindness (Bascom Palmer Eye Institute, Flaum Eye Institute); National Institutes of Health (NIE P30EY 001319); Unrestricted Funds Research to Prevent Blindness, NY; National Institutes of Health (R01EY021834); National Institutes of Health (P30EY014801); Florida Lions Eye Bank and Beauty of Sight Foundation; Hyderabad Eye Research Foundation.

Objectives With a fourth of all under-five children affected, stunting remains one of the biggest health challenges worldwide. Even though the main underlying factors are known, the exact pathways to stunting varying in affected regions, and interventions thus need to be tailored to the local contexts. This study aimed assessing and comparing factors associated with stunting in two understudied sub-Saharan urban contexts with some of the highest stunting prevalence globally: Bangui, Central African Republic (~ 36%) and Antananarivo, Madagascar (42%). Methods We performed a case–control study on 175 + 194 stunted and 237 + 230 non-stunted control children aged 2–5 years and matched for age, gender and district of residency. Factors associated with stunting were identified using a standardized, paper questionnaire delivered by trained interviewers. Statistical analysis was done using logistic regression modelling. Results In both sites, formal maternal education lowered the risk of being stunted and restricted access to soap, suffering of anaemia and low birth weight were associated with higher risk of stunting. Short maternal stature, household head different from parents, diarrhoea and coughing were associated with an increased risk and continuing breastfeeding was associated with a lower risk of stunting in Antananarivo. Previous severe undernutrition and dermatitis/ fungal skin infections were associated with higher and changes in diet during pregnancy with lower risk of stunting in Bangui. Conclusions Our results suggest maternal education, antenatal care, iron supplementation and simple WASH interventions such as using soap and infection control as general and breastfeeding (Antananarivo) or better nutrition (Bangui) as area-specified interventions. Supplementary Information The online version contains supplementary material available at 10.1007/s10995-021-03201-8.

NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. The core mechanism for this form of plasticity is thought to be entirely neuronal. However, we now demonstrate that astrocytic activity drives LTD at CA3-CA1 synapses. We have found that LTD induction enhances astrocyte-to-neuron communication mediated by glutamate, and that Ca2+ signaling and SNARE-dependent vesicular release from the astrocyte are required for LTD expression. In addition, using optogenetic techniques, we show that low-frequency astrocytic activation, in the absence of presynaptic activity, is sufficient to induce postsynaptic AMPA receptor removal and LTD expression. Using cell-type-specific gene deletion, we show that astrocytic p38α MAPK is required for the increased astrocytic glutamate release and astrocyte-to-neuron communication during low-frequency stimulation. Accordingly, removal of astrocytic (but not neuronal) p38α abolishes LTD expression. Finally, this mechanism modulates long-term memory in vivo., How astrocytes influence neuronal plasticity remains unclear, as they are typically considered as modulators of core mechanisms driven by neuronal components. Here, authors show that Long-term depression (LTD) induction in the hippocampus triggers calcium signaling in the astrocyte and enhances SNARE-dependent astrocytic glutamate release, which is then responsible for the activation of postsynaptic NMDA receptors and synaptic depression.

Aluminum (Al), which is omnipresent in human life, is a potent neurotoxin. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against changes in cognitive function in rats exposed to both high and low levels of Al. Indeed, EWH has been previously shown to improve the negative effects induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl3 at a dose of 8.3 mg/kg b.w. during 60 days) with or without EWH treatment (1 g/kg/day); Group 2) High aluminum level (AlCl3 at a dose of 100 mg/kg b.w. during 42 days) with or without EWH treatment (1 g/kg/day). After 60 or 42 days of exposure, rats exposed to Al and EWH did not show memory or cognitive dysfunction as was observed in Al-treated animals. Indeed, co-treatment with EWH prevented catalepsy, hippocampal oxidative stress, cholinergic dysfunction and increased number of activated microglia and COX-2-positive cells induced by Al exposure. Altogether, since hippocampal inflammation and oxidative damage were partially prevented by EWH, our results suggest that it could be used as a protective agent against the detrimental effects of long term exposure to Al., This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq 406715/2013-0, 203503/2015-5]; the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Programa Nacional de Cooperação Acadêmica; Pró-reitoria de Pesquisa - Universidade Federal do Pampa [N°10.134.14] and by the Spanish Goverment [MINECO - AGL2012-32387, CSIC – Intramural 201570I028 and SAF2015-69294-R]. PBMC was supported by For Women in Science Program – L’Oreal Foundation and UNESCO.

The design of complex, competing effects in magnetic systems – be it via the introduction of nonlinear interactions, or the patterning of three-dimensional geometries – is an emerging route to achieve new functionalities. Here, we combine 3D geometric effects with non-linear and non-local interactions to produce magnetic field textures in free space. For this, we harness direct write nanofabrication techniques, creating intertwined nanomagnetic cobalt double helices, where curvature, torsion, chirality, and magnetic coupling are jointly exploited. By reconstructing the 3D vectorial magnetic state of the double helices with soft X-ray magnetic laminography, we identify the presence of a regular array of highly coupled locked domain wall pairs in neighbouring helices. Micromagnetic simulations reveal that the magnetisation configuration leads to the formation of an array of complex textures in the magnetic induction, consisting of vortices in the magnetisation and antivortices in free space, which together, form an effective B-field cross-tie wall. The design and creation of complex three-dimensional magnetic field nanotextures opens new possibilities for smart materials, unconventional computing, particle trapping and magnetic imaging., This work was funded by an EPSRC Early Career Fellowship EP/M008517/1 and the Winton Program for the Physics of Sustainability. C.D. acknowledges funding from the Leverhulme Trust (ECF-2018-016), the Isaac Newton Trust (18-08), the L’Oréal-UNESCO UK and Ireland Fellowship For Women In Science 2019, and the Max Planck Society Lise Meitner Excellence Program. A.F.P. acknowledges funding by the European Community under the Horizon 2020 Program, Contract no. 101001290, 3DNANOMAG. A.H.-R. and S.MV. acknowledge the support from European Union’s Horizon 2020 research and innovation program under Marie Skłodowska-Curie grant ref. H2020-MSCA-IF-2016-746958. A.H.-R. acknowledges funding from Spanish AEI under project reference PID2019–104604RB/AEI/10.13039/501100011033. The PolLux end station was financed by the German Ministerium für Bildung und Forschung (BMBF) through contracts 05K16WED and 05K19WE2. K.W. acknowledges the funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 701647. A.F.P. is grateful to the University of Cambridge and the University of Glasgow, where part of this research was performed.

Background This study aimed to compare the prevalence of intestinal parasite infestations (IPIs) in stunted children, compared to control children, in Ankasina and Andranomanalina Isotry (two disadvantaged neighborhoods of Antananarivo, Madagascar), to characterize associated risk factors and to compare IPI detection by real-time PCR and standard microscopy techniques. Methodology/Principal findings Fecal samples were collected from a total of 410 children (171 stunted and 239 control) aged 2–5 years. A single stool sample per subject was examined by simple merthiolate-iodine-formaldehyde (MIF), Kato-Katz smear and real-time PCR techniques. A total of 96.3% of the children were infested with at least one intestinal parasite. The most prevalent parasites were Giardia intestinalis (79.5%), Ascaris lumbricoides (68.3%) and Trichuris trichiura (68.0%). For all parasites studied, real-time PCR showed higher detection rates compared to microscopy (G. intestinalis [77.6% (n = 318) versus 20.9% (n = 86)], Entamoeba histolytica [15.8% (n = 65) versus 1.9% (n = 8)] and A. lumbricoides [64.1% (n = 263) versus 50.7% (n = 208)]). Among the different variables assessed in the study, age of 4 to 5 years (AOR = 4.61; 95% CI, (1.35–15.77)) and primary and secondary educational level of the mother (AOR = 12.59; 95% CI, (2.76–57.47); AOR = 9.17; 95% CI, (2.12–39.71), respectively) were significantly associated with IPIs. Children drinking untreated water was associated with infestation with G. intestinalis (AOR = 1.85; 95% CI, (1.1–3.09)) and E. histolytica (AOR = 1.9; 95% CI, (1.07–3.38)). E. histolytica was also associated with moderately stunted children (AOR = 0.37; 95% CI, 0.2–0.71). Similarly, children aged between 4 and 5 years (AOR = 3.2; 95% CI (2.04–5.01)) and living on noncemented soil types (AOR = 1.85; 95% CI, (1.18–2.09)) were associated with T. trichiura infestation. Conclusions/Significance The prevalence of IPIs is substantial in the studied areas in both stunted and control children, despite the large-scale drug administration of antiparasitic drugs in the country. This high prevalence of IPIs warrants further investigation. Improved health education, environmental sanitation and quality of water sources should be provided., Author summary In populations living in adverse conditions due to poverty, a wide variety of intestinal parasite infestations can be observed. These infestations are usually diagnosed by stool microscopy but can be easily overlooked if the procedures used are inaccurate or performed in a suboptimal way. In the present study, we investigated the prevalence of intestinal parasite infestations in stunted and control children aged from 2 to 5 years living in two disadvantaged neighborhoods of Antananarivo Madagascar. We also assessed risk factors for infestations and the diagnostic performance of microscopic techniques and real-time PCR for the detection of parasites. Almost all individuals were found to be infested with at least one parasitic species. Children aged between 4 and 5 years and mothers with low educational levels were found to be associated with infestation. Similarly, children drinking untreated water were associated with G. intestinalis and E. histolytica infestation. This latter species was also associated with moderately stunted children. Children between 4 and 5 years old and with no cemented soil type were associated with T. trichiura infestation. The high prevalence of intestinal parasite infestations among the study participants requires the improvement of health education, environmental sanitation and quality of water sources.

Background Child undernutrition is a global health issue that is associated with poor sanitation and an altered intestinal microbiota. Immunoglobulin (Ig) A mediates host-microbial homeostasis in the intestine, and acutely undernourished children have been shown to have altered IgA recognition of the fecal microbiota. We sought to determine whether chronic undernutrition (stunting) or intestinal inflammation were associated with antibody recognition of the microbiota using two geographically distinct populations from the Afribiota project. Fecal bacteria from 200 children between 2 and 5 years old in Antananarivo, Madagascar, and Bangui, Central African Republic (CAR), were sorted into IgA-positive (IgA+) and IgA-negative (IgA−) populations by flow cytometry and subsequently characterized by 16S rRNA gene sequencing to determine IgA-bacterial targeting. We additionally measured IgG+ fecal bacteria by flow cytometry in a subset of 75 children. Results Stunted children (height-for-age z-score ≤ −2) had a greater proportion of IgA+ bacteria in the fecal microbiota compared to non-stunted controls. This trend was consistent in both countries, despite the higher overall IgA-targeting of the microbiota in Madagascar, but lost significance in each country individually. Two of the most highly IgA-recognized bacteria regardless of nutritional status were Campylobacter (in CAR) and Haemophilus (in both countries), both of which were previously shown to be more abundant in stunted children; however, there was no association between IgA-targeting of these bacteria and either stunting or inflammatory markers. IgG-bound intestinal bacteria were rare in both stunted and non-stunted children, similar to levels observed in healthy populations. Conclusions Undernourished children carry a high load of intestinal pathogens and pathobionts. Our data suggest that stunted children have a greater proportion of IgA-recognized fecal bacteria. We moreover identify two putative pathobionts, Haemophilus and Campylobacter, that are broadly targeted by intestinal IgA. This study furthers our understanding of host-microbiota interactions in undernutrition and identifies immune-recognized microbes for future study.

8 Figuras.- 4 Tablas, Pd and PdM (M = Fe or Co) nanostructured electrocatalysts were synthesized by the impregnation method and supported on carbon black Vulcan XC-72R for the formic acid oxidation reaction, FAOR, in acid medium. Nitrates or chlorides were used as Fe and Co precursors to study the counter ion role on the physicochemical features and electrochemical performance of the electrocatalysts. TEM analysis showed that PdM was deposited on the carbon material with a particle size around 2–3 nm. From XRD, peaks associated with the fcc palladium planes were observed along with evidence of PdM alloy formation, particularly when the nitrate salts were used as metal precursors. Furthermore, XPS analyses indicated that nitrates promote the metal oxide formation to a greater extent than chlorides, mainly for Pd. PdCo electrocatalyst obtained from nitrates exhibited the highest performance for FAOR with a steady state current density of 451 and 313 μA cm−2 at 200 and 400 mV respectively, which is in both cases, 3 times larger than that developed for a commercial Pd/C catalyst., LJM is grateful to CONACYT for the grant awarded for this research, as well as to the UAM-A and the ICB for the support provided. MGMY, MRR, MPP and AEM thank the SNI for the distinction of their membership and the stipend provided. MGMY is indebted to L'oreál-UNESCO-CONACyT-AMC for the grant Women in Science 2016. MJL and SPR gratefully acknowledge financial support given by Spanish MINECO (ENE2014-52158-C2-1-R).

Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising cell therapy in regenerative medicine and for autoimmune/inflammatory diseases. However, a main hurdle for MSCs‐based therapies is the loss of their proliferative potential in vitro. Here we report that glycoprotein A repetitions predominant (GARP) is required for the proliferation and survival of adipose‐derived MSCs (ASCs) via its regulation of transforming growth factor‐β (TGF‐β) activation. Silencing of GARP in human ASCs increased their activation of TGF‐β which augmented the levels of mitochondrial reactive oxygen species (mtROS), resulting in DNA damage, a block in proliferation and apoptosis. Inhibition of TGF‐β signaling reduced the levels of mtROS and DNA damage and restored the ability of GARP−/lowASCs to proliferate. In contrast, overexpression of GARP in ASCs increased their proliferative capacity and rendered them more resistant to etoposide‐induced DNA damage and apoptosis, in a TGF‐β‐dependent manner. In summary, our data show that the presence or absence of GARP on ASCs gives rise to distinct TGF‐β responses with diametrically opposing effects on ASC proliferation and survival., Silencing of glycoprotein A repetitions predominant (GARP) in adipose‐derived mesenchymal stromal cells (ASCs) increases the activation of transforming growth factor‐β (TGF‐β), resulting in mitochondrial reactive oxygen species‐dependent DNA damage, inhibition of proliferation, and apoptosis. In contrast, overexpression of GARP induces a TGF‐β response characterized by an increased resistance to DNA damage, increased proliferation, and a reduction in apoptosis. We show that GARP is critical in controlling TGF‐β activation/signaling in ASCs during in vitro expansion.

Chirality plays a major role in nature, from particle physics to DNA, and its control is much sought-after due to the scientific and technological opportunities it unlocks. For magnetic materials, chiral interactions between spins promote the formation of sophisticated swirling magnetic states such as skyrmions, with rich topological properties and great potential for future technologies. Currently, chiral magnetism requires either a restricted group of natural materials or synthetic thin-film systems that exploit interfacial effects. Here, using state-of-the-art nanofabrication and magnetic X-ray microscopy, we demonstrate the imprinting of complex chiral spin states via three-dimensional geometric effects at the nanoscale. By balancing dipolar and exchange interactions in an artificial ferromagnetic double-helix nanostructure, we create magnetic domains and domain walls with a well-defined spin chirality, determined solely by the chiral geometry. We further demonstrate the ability to create confined 3D spin textures and topological defects by locally interfacing geometries of opposite chirality. The ability to create chiral spin textures via 3D nanopatterning alone enables exquisite control over the properties and location of complex topological magnetic states, of great importance for the development of future metamaterials and devices in which chirality provides enhanced functionality., This work was funded by EPSRC Early Career Fellowship EP/M008517/1, the Winton Program for the Physics of Sustainability, and the EU CELINA COST action. D.S.-H. acknowledges a Girton College Pfeiffer scholarship and support from the EPSRC CDT in Nanoscience and Nanotechnology. A.H.-R. and S.M.V. acknowledge funding from the EU Horizon 2020 program through Marie Skłodowska-Curie Action H2020-MSCA-IF-2016-74695. C.D. acknowledges funding from Leverhulme Trust (ECF-2018-016), Isaac Newton Trust (18-08), and a L’Oréal-UNESCO UK and Ireland Fellowship for Women in Science 2019. Funding by the Spanish Ministry of Science is acknowledged, grants MAT2017-82970-C2-1-R, MAT2017-82970-C2-2-R and MAT2018-102627-T, and by Aragon Government (Construyendo Europa desde Aragón), grant E13_20R including European Social Fund. J.P.-N. acknowledges MINECO funding BES-2015-072950. S.M.V. appreciates support from EPSRC EP/M024423/1. P.F. was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division, Contract No. DE-AC02-05-CH11231 (NEMM program MSMAG). These experiments were performed at MISTRAL beamline at ALBA Synchrotron with the collaboration of ALBA staff and CALIPSOplus (Grant 730872) funding.

Nicotinic acetylcholine receptors (nAChRs) modulate the cholinergic drive to a hierarchy of inhibitory neurons in the superficial layers of the PFC, critical to cognitive processes. It has been shown that genetic deletions of the various types of nAChRs impact the properties of ultra-slow transitions between high and low PFC activity states in mice during quiet wakefulness. The impact characteristics depend on specific interneuron populations expressing the manipulated receptor subtype. In addition, recent data indicate that a genetic mutation of the α5 nAChR subunit, located on vasoactive intestinal polypeptide (VIP) inhibitory neurons, the rs16969968 single nucleotide polymorphism (α5 SNP), plays a key role in the hypofrontality observed in schizophrenia patients carrying the SNP. Data also indicate that chronic nicotine application to α5 SNP mice relieves the hypofrontality. We developed a computational model to show that the activity patterns recorded in the genetically modified mice can be explained by changes in the dynamics of the local PFC circuit. Notably, our model shows that these altered PFC circuit dynamics are due to changes in the stability structure of the activity states. We identify how this stability structure is differentially modulated by cholinergic inputs to the parvalbumin (PV), somatostatin (SOM) or the VIP inhibitory populations. Our model uncovers that a change in amplitude, but not duration of the high activity states can account for the lowered pyramidal (PYR) population firing rates recorded in α5 SNP mice. We demonstrate how nicotine-induced desensitization and upregulation of the β2 nAChRs located on SOM interneurons, as opposed to the activation of α5 nAChRs located on VIP interneurons, is sufficient to explain the nicotine-induced activity normalization in α5 SNP mice. The model further implies that subsequent nicotine withdrawal may exacerbate the hypofrontality over and beyond one caused by the SNP mutation., Graphical abstract Image 1, Highlights • Prefrontal cortex shows ultra-slow alterations between low and high activity states at rest. This activity is characteristically decreased in schizophrenia patients. • Model identifies local circuit origin of hypofrontality associated with schizophrenia and a5 nicotinic receptor malfunction. • Decrease in PFC VIP-interneuron excitability drives decrease in high-activity-state stability and overall hypofrontality. • Model shows desensitization/upregulation of SOM-expressed β2-NAChRs drive nicotine-induced renormalization of PFC activity.

The synthesis and full characterization of a family of sustainable luminescent nanoparticles, CdTeQDs@MNs, made of quantum dots coated by modified mesoporous silica nanoparticles is reported. The presence of the luminescent QDs allows the imaging of the nanoparticles during cell internalization, as well as the visualization of selective release of doxorubicin inside the cell (via pH stimuli). The modified mesoporous silica nanoparticles lead to pore size improvement allowing better encapsulation and controlled release, of different active principles studied such as, small molecules (rhodamine B), drugs (doxorubicin), and isolated proteins such as bovine serum albumin, lysozyme, carbonic anhydrase, ovalbumin, α-lactalbumin, hemoglobin, myoglobin and cytochrome C. Finally, and as a proof-of-concept the efficacy of these novel platforms was demonstrated through the successful extraction and recognition of proteins in raw serum of osteoarthritis and prosthesis patients, without any previous protein depletion., This work was supported by PROTEOMASS Scientific Society (Portugal) and LAQV/REQUIMTE (UID/QUI/50006/2013). D.R-M and F.N. want to thanks project MAT2015-70615-R from the Spanish Government and by FEDER funds. ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295). J. L acknowledges support from project BIO2016-08057-R from MINECO-Spain. EO and SJ acknowledge the Post-Doctoral and Doctoral grants SFRH/BPD/108660/2015 and SFRH/BD/120537/2016, respectively, from Fundação para a Ciência e a Tecnologia (FCT-MEC) Portugal. EO thanks to Foundation L'Oreal (UNESCO and FCT) for the Prize Women in Science 2015, “Medalhas de Honra L’Oréal Portugal para as Mulheres na Ciência”. We also thank to Ms. Jessica Ariana-Machado for her help in the physical characterization (IR studies). H.M.S. is funded by the FCT 2015 Investigator Program (IF/00007/2015).

Mothers may vary resource allocation to eggs and embryos, which may affect offspring fitness and prepare them for future environmental conditions. The effects of food availability and predation risk on reproduction have been extensively studied, yet their simultaneous impacts on reproductive investment and offspring early life conditions are still unclear. We experimentally manipulated these key environmental elements using a 2×2 full factorial design in wild, free-living pied flycatchers (Ficedula hypoleuca), and measured egg composition, eggshell traits and offspring condition. Eggs laid in food-supplemented nests had larger yolks and thicker shells independently of predation risk, while eggs laid in nests exposed to predator cues had lower levels of immunoglobulins, independent of food supplementation. In nests without predator cues, shell biliverdin content was higher in eggs laid in food-supplemented nests. Incubation was 1 day shorter in food-supplemented nests and shorter incubation periods were associated with higher hatching success, but there were no direct effects of maternal treatment on hatching success. To investigate the impact of maternal treatment (via egg composition) on the offspring, we performed full brood cross-fostering after hatching to unmanipulated nests. Maternal treatment did not significantly affect body mass and immunoglobulin levels of offspring. Our results suggest that although prenatal maternal cues affected egg composition, these egg-mediated effects may not have detectable consequences for offspring growth or immune capacity. Unpredictable environmental stressors may thus affect parental investment in the eggs, but parental care may level off costs and benefits of differential maternal egg allocation., The project was funded by the Finnish Cultural Foundation (Suomen Kulttuurirahasto)-South Ostrobothnia Regional Fund and the L'Oréal-UNESCO For Women in Science award (personal grants to C.M.), and the Academy of Finland (projects 138049 to R.L.T. and 258419 to S.R.).

Ferroelectric perovskite oxides are emerging as a promising photoactive layer for photovoltaic applications due to their very high stability and their alternative ferroelectricity-related mechanism for solar energy conversion that could lead to extraordi-narily high efficiencies. One of the biggest challenges so far is to reduce their band gap towards the visible while simultane-ously retaining ferroelectricity. To address these two issues, herein it is performed an elemental composition engineering of BiFeO3 by substituting Fe by Co cations, as means to tune the characteristics of the transition metal-oxygen bond. We demonstrate by solution processing the formation of epitaxial, pure phase and stable BiFe1-xCoxO3 thin films for x=0.3 and film thickness up to 100 nm. Importantly, the band gap can be tuned from 2.7 eV to 2.3 eV upon cobalt substitution while simultaneously enhancing ferroelectricity. As a proof of concept, non-optimized vertical devices have been fabricated and, reassuringly, the electrical photoresponse in the visible of the Co-substituted phase is improved with respect to the unsubsti-tuted oxide., We would like to acknowledge Prof. Josep Fontcuberta for fruitful discussions and comments on this study and for providing access to his experimental facilities. This research was supported by the Spanish MINECO (“Severo Ochoa” Programme for Centres of Excellence in R&D SEV-2015-0496 and FIPNANOSOLE- 2016, MAT2017-83169-R, MAT2014-51778-C2- 1-R, MAT2015-70850-P, MAT2017-85232-R (AEI/FEDER, EU)), the Generalitat de Catalunya (2017-SGR-1519, 2017 SGR- 1377), the European Research Council-ERC (FOREMAT under grant agreement no. 648901) and “L’Oreal UNESCO For Women in Science”. M.C., J.G. and I.F. acknowledge RyC contracts (2013-12448, 2012-11709 and RYC-2017-22531). I.F. is grateful to MINECO for MAT2015-73839-JIN project. The HRTEM microscopy work was conducted at the Center for Nanophase Materials Sciences at Oak Ridge National Laboratory, which is a DOE Office of Science User Facility.

International audience; Even though tremendous progress has been made in the last decades to elucidate the mechanisms of intestinal homeostasis, dysbiosis and disease, we are only at the beginning of understanding the complexity of the gut ecosystem and the underlying interaction networks. We are also only starting to unravel the mechanisms that pathogens have evolved to overcome the barriers imposed by the microbiota and host to exploit the system to their own benefit. Recent work in these domains clearly indicates that the 'traditional Koch's postulates', which state that a given pathogen leads to a distinct disease, are not valid for all 'infectious' diseases, but that a more complete and complex interpretation of Koch's postulates is needed in order to understand and explain them. This review summarises the current understanding of what defines a healthy gut ecosystem and highlights recent progress in uncovering the interplay between the host, its microbiota and invading intestinal pathogens. Based on these recent findings, we propose a new interpretation of Koch's postulates that we term 'ecological Koch's postulates'.

In this work, we present a substrate removal procedure for solar cells compatible with direct attachment of the epitaxy to a holder through a thermally and electrically conductive interface. In our case this procedure was motivated by the need to develop a processing technique compatible with low-temperature characterization of the devices. The method is based on the use of indium to bond a thin-film epitaxial structure to a silicon support. The adequate properties of indium, namely, low tensile strength and good thermal and electrical conductivity, allow characterizing the devices at very low temperatures without causing strain-induced degradation in the samples. Following this method, we have fabricated and characterized thin-film (1.74 µm) AlGaAs solar cells with and without a layer of InAs quantum dots. We show the adequacy of our method to measure at low temperatures by means of measuring the photocurrent or quantum efficiency of the devices at different temperatures, ranging from 300 K to 20 K., J. Villa is grateful for the financing of the Spanish Government through the Grant BES-2013–066463. This work has been supported by Comunidad de Madrid through the Project MADRID-PV (Grant S2013/MAE-2780) and by the Spanish National Research Programs through the Projects INVENTA-PV (Grant TEC2015-64189-C3-1-R) and POWERLEO (Grant RTC-2015–3469-3). E. Antolín acknowledges financial support from L’Oréal-UNESCO through a Women in Science Fellowship. I. García is funded by the Spanish Programa Estatal de Promoción del Talento y su Empleabilidad through a Ramón y Cajal grant.

p–n junctions based on vertically stacked single or few-layer transition metal dichalcogenides (TMDCs) have attracted substantial scientific interest. Due to the propensity of TMDCs to show exclusively one type of conductivity, n- or p-type, heterojunctions of different materials are typically fabricated to produce diode-like current rectification and photovoltaic response. Recently, artificial, stable and substitutional doping of MoS2 into n- and p-type materials has been demonstrated. MoS2 is an interesting material for use in optoelectronic applications due to its potential of low-cost production in large quantities, strong light–matter interactions and chemical stability. Here we report the characterization of the optoelectronic properties of vertical homojunctions made by stacking few-layer flakes of MoS2:Fe (n-type) and MoS2:Nb (p-type). The junctions exhibit a peak external quantum efficiency of 4.7% and a maximum open circuit voltage of 0.51 V; they are stable in air; and their rectification characteristics and photovoltaic response are in excellent agreement with the Shockley diode model. The gate-tunability of the maximum output power, the ideality factor and the shunt resistance indicate that the dark current is dominated by trap-assisted recombination and that the photocurrent collection depends strongly on the spatial extent of the space charge region. We demonstrate a response time faster than 80 ms and highlight the potential to integrate such devices into quasi-transparent and flexible optoelectronics., S. A. S. and N. A. acknowledge funding from the European Commission through the FP7 ITN MOLESCO (Project Number 606728). E. A. gratefully acknowledges financial support from L’Oréal-UNESCO through the Women in Science program. A. J. M.-M. acknowledges the financial support from MICINN (Spain) through the scholarship BES-2012-057346. D. Y. and T. S. acknowledge the support from the Ministry of Science and Technology of the Republic of China under the MOST 104-2112-M-018-004 and 104-2221-E-018-017. D. P. is thankful for funding from the Spanish Ministry of Economy and Competitiveness through FIS2015-67367-C2-1-P. R. F. thanks the Netherlands Organisation for Scientific Research (NWO) for the financial support through the research programme Rubicon with the project number 680-50-1515. AC-G. acknowledges the support from the BBVA Foundation through the fellowship “I Convocatoria de Ayudas Fundacion BBVA a Investigadores, Innovadores y Creadores Culturales” (“Semiconductores ultradelgados: hacia la optoelectronica flexible”), from the MINECO (Ramón y Cajal 2014 program, RYC-2014-01406), from the MICINN (MAT2014-58399-JIN) and from the Comunidad de Madrid (MAD2D-CM Program (S2013/MIT-3007)), and the European Commission under the Graphene Flagship, contract CNECTICT-604391.

4 Figuras, 1 Tabla., [EN] Pd, PdCo and PdFe catalysts were prepared by the impregnation method, using sodium borohydride (NaBH4) as the reducing agent and a commercial carbon material (Vulcan XC-72R) as support. The synthesized electrocatalysts were tested for the formic acid oxidation reaction (FAOR) in acid medium (H2SO4 0.5 M). The morphology, composition and particle size of the electrocatalysts were characterized by physicochemical techniques as X-ray diffraction (XRD), scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). The catalytic activity was evaluated by cyclic voltammetry (CV) and chronoamperometry techniques (CA)., [ES] Catalizadores de Pd, PdFe y PdCo fueron preparados por el método de impregnación, usando borohidruro de sodio (NaBH4) como agente reductor y un material de carbono comercial, (Vulcan XC-72R) como soporte. Los electrocatalizadores sintetizados fueron probados para la reacción de oxidación de ácido fórmico (FAOR, por sus siglas en inglés) en medio ácido (H2SO4 0,5 M). La morfología, la composición y el tamaño de partícula de los electrocatalizadores se caracterizaron mediante técnicas físico-químicas como difracción de rayos X (XRD), microscopía electrónica de barrido con espectroscopia por energía dispersiva (SEM-EDS) y microscopia electrónica de transmisión (TEM). La actividad catalítica se evaluó mediante técnicas de voltamperometría cíclica (CV) y cronoamperometría (CA)., LJM agradece a CONACyT por la beca otorgada para la realización de los estudios de Maestría, así como a UAM-A, ICB, IPN por el apoyo otorgado para la realización de este trabajo. MGMY, MRR, MEPP y AEM agradecen al SNI. MGMY agradece a L ́oreal-UNESCO-CONACyT-AMC por la beca en Mujeres en la Ciencia 2016. MJL and SPR agradecen al Gobierno de Aragón (DGA) y FEDER por la financiación a través del Grupo de Investigación Conversión de Combustibles (T06_17R)