Prox2 and Runx3 vagal sensory neurons regulate esophageal motility.

Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we use genetically guided anatomical tracing, optogenetics, and electrophysiology to identify and characterize vagal sensory neuron subtypes expressing Prox2 and Runx3 in mice. We show that three of these neuronal subtypes innervate the esophagus and stomach in regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological analysis revealed that they are low-threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis in freely behaving mice. Our work defines the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.

Molecular identity of proprioceptor subtypes innervating different muscle groups in mice.

The precise execution of coordinated movements depends on proprioception, the sense of body position in space. However, the molecular underpinnings of proprioceptive neuron subtype identities are not fully understood. Here we used a single-cell transcriptomic approach to define mouse proprioceptor subtypes according to the identity of the muscle they innervate. We identified and validated molecular signatures associated with proprioceptors innervating back (Tox, Epha3), abdominal (C1ql2), and hindlimb (Gabrg1, Efna5) muscles. We also found that proprioceptor muscle identity precedes acquisition of receptor character and comprise programs controlling wiring specificity. These findings indicate that muscle-type identity is a fundamental aspect of proprioceptor subtype differentiation that is acquired during early development and includes molecular programs involved in the control of muscle target specificity.

Economic development, weather shocks and child marriage in South Asia: A machine learning approach.

Globally, 21 percent of young women are married before their 18th birthday. Despite some progress in addressing child marriage, it remains a widespread practice, in particular in South Asia. While household predictors of child marriage have been studied extensively in the literature, the evidence base on macro-economic factors contributing to child marriage and models that predict where child marriage cases are most likely to occur remains limited. In this paper we aim to fill this gap and explore region-level indicators to predict the persistence of child marriage in four countries in South Asia, namely Bangladesh, India, Nepal and Pakistan. We apply machine learning techniques to child marriage data and develop a prediction model that relies largely on regional and local inputs such as droughts, floods, population growth and nightlight data to model the incidence of child marriages. We find that our gradient boosting model is able to identify a large proportion of the true child marriage cases and correctly classifies 77% of the true marriage cases, with a higher accuracy in Bangladesh (92% of the cases) and a lower accuracy in Nepal (70% of cases). In addition, all countries contain in their top 10 variables for classification nighttime light growth, a shock index of drought over the previous and the last two years and the regional level of education, suggesting that income shocks, regional economic activity and regional education levels play a significant role in predicting child marriage. Given the accuracy of the model to predict child marriage, our model is a valuable tool to support policy design in countries where household-level data remains limited.

Rabies Anterograde Monosynaptic Tracing Allows Identification of Postsynaptic Circuits Receiving Distinct Somatosensory Input.

Somatosensory neurons detect vital information about the environment and internal status of the body, such as temperature, touch, itch, and proprioception. The circuit mechanisms controlling the coding of somatosensory information and the generation of appropriate behavioral responses are not clear yet. In order to address this issue, it is important to define the precise connectivity patterns between primary sensory afferents dedicated to the detection of different stimuli and recipient neurons in the central nervous system. In this study we describe and validate a rabies tracing approach for mapping mouse spinal circuits receiving sensory input from distinct, genetically defined, modalities. We analyzed the anatomical organization of spinal circuits involved in coding of thermal and mechanical stimuli and showed that somatosensory information from distinct modalities is relayed to partially overlapping ensembles of interneurons displaying stereotyped laminar organization, thus highlighting the importance of positional features and population coding for the processing and integration of somatosensory information.

Determinants and drivers of young children's diets in Latin America and the Caribbean: Findings from a regional analysis.

The Latin America and Caribbean region exhibit some of the lowest undernutrition rates globally. Yet, disparities exist between and within countries and countries in the region increasingly face other pressing nutritional concerns, including overweight, micronutrient deficiencies and inadequate child feeding practices. This paper reports findings from a regional analysis to identify the determinants and drivers of children's diets, with a focus on the complementary feeding window between the age of 6-23 months. The analysis consists of a narrative review and descriptive data analysis, complemented with qualitative interviews with key informants in four countries: Guatemala, Paraguay, Peru and Uruguay. Findings indicate that poverty and inequality (disparities within countries by wealth and residence), unequal access to services, inadequate coverage of social programmes and lack of awareness on appropriate feeding practices are important drivers for inadequate diets. We conclude that countries in the region need to invest in policies to tackle overweight and micronutrient deficiencies in young children, considering inequalities between and within countries, enhance coverage of social protection programmes, improve coordination between sectors to improve children's diets and expand the coverage and intensity of awareness campaigns on feeding practices, using iterative programme designs.

Nontoxic, double-deletion-mutant rabies viral vectors for retrograde targeting of projection neurons.

Recombinant rabies viral vectors have proven useful for applications including retrograde targeting of projection neurons and monosynaptic tracing, but their cytotoxicity has limited their use to short-term experiments. Here we introduce a new class of double-deletion-mutant rabies viral vectors that left transduced cells alive and healthy indefinitely. Deletion of the viral polymerase gene abolished cytotoxicity and reduced transgene expression to trace levels but left vectors still able to retrogradely infect projection neurons and express recombinases, allowing downstream expression of other transgene products such as fluorophores and calcium indicators. The morphology of retrogradely targeted cells appeared unperturbed at 1 year postinjection. Whole-cell patch-clamp recordings showed no physiological abnormalities at 8 weeks. Longitudinal two-photon structural and functional imaging in vivo, tracking thousands of individual neurons for up to 4 months, showed that transduced neurons did not die but retained stable visual response properties even at the longest time points imaged.

Non-thermal plasma activates human keratinocytes by stimulation of antioxidant and phase II pathways.

Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application.

Early failure of a press-fit carbon fiber hip prosthesis with a smooth surface.

We investigated a press-fit anatomically shaped hip stem made of carbon fiber-reinforced composite material in a prospective clinical study. The intention of the design was that a surface of interlaced carbon fibers in the proximal part would achieve metaphyseal fixation. A total of 51 carbon stems were implanted in 48 patients (30 women and 22 men). Mean age at operation was 59 years. The patients were followed clinically, radiologically, and with computed tomography. At 6-year follow-up, aseptic loosening was observed in 47 hips (92%). Forty stems were revised on average 30 months (range, 9-58 months) postoperatively. All revised carbon stems showed fibrous fixation without any bony on-growth. No osteolysis was seen. Histologically, no carbon wear or inflammatory reactions were observed. Only 4 cases had a good clinical result with bony fixation on computed tomography scan. The carbon fiber prosthesis without effective ingrowth or on-growth irregularities showed a high rate of early loosening.