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This article investigates whether public investments that led to improvements in road quality and increased access to agricultural extension services led to faster consumption growth and lower rates of poverty in rural Ethiopia. Estimating an Instrumental Variables model using Generalized Methods of Moments and controlling for household fixed effects, we find evidence of positive impacts with meaningful magnitudes. Receiving at least one extension visit reduces headcount poverty by 9.8 percentage points and increases consumption growth by 7.1 percentage points. Access to all-weather roads reduces poverty by 6.9 percentage points and increases consumption growth by 16.3 percentage points. These results are robust to changes in model specification and estimation methods.

We evaluate causal impacts of a large-scale agricultural extension program for smallholder women farmers on technology adoption and food security in Uganda through a regression discontinuity design that exploits an arbitrary distance-to-branch threshold for village program eligibility. We find eligible farmers used better basic cultivation methods, achieved improved food security. Given minimal changes in adoption of relatively expensive inputs, we attribute these gains to improved cultivation methods that require low upfront monetary investment. Farmers also modified their shock-coping methods. These results highlight the role of information and training in boosting agricultural productivity among poor farmers and, indirectly, improving food security.

The orchestration of intercellular communication is essential for multicellular organisms. One mechanism by which cells communicate is through long, actin-rich membranous protrusions called tunneling nanotubes (TNTs), which allow the intercellular transport of various cargoes, between the cytoplasm of distant cells in vitro and in vivo. With most studies failing to establish their structural identity and examine whether they are truly open-ended organelles, there is a need to study the anatomy of TNTs at the nanometer resolution. Here, we use correlative FIB-SEM, light- and cryo-electron microscopy approaches to elucidate the structural organization of neuronal TNTs. Our data indicate that they are composed of a bundle of open-ended individual tunneling nanotubes (iTNTs) that are held together by threads labeled with anti-N-Cadherin antibodies. iTNTs are filled with parallel actin bundles on which different membrane-bound compartments and mitochondria appear to transfer. These results provide evidence that neuronal TNTs have distinct structural features compared to other cell protrusions. The architecture of functional TNTs is still under debate. Here, the authors combine correlative FIB-SEM, light- and cryo-electron microscopy approaches to elucidate the structure of TNTs in neuronal cells, showing that they form structures that are distinct form other membrane protrusions.

Standard experimental designs are geared toward point estimation and hypothesis testing, while bandit algorithms are geared toward in-sample outcomes. Here, we instead consider treatment assignment in an experiment with several waves for choosing the best among a set of possible policies (treatments) at the end of the experiment. We propose a computationally tractable assignment algorithm that we call “exploration sampling,” where assignment probabilities in each wave are an increasing concave function of the posterior probabilities that each treatment is optimal. We prove an asymptotic optimality result for this algorithm and demonstrate improvements in welfare in calibrated simulations over both non-adaptive designs and bandit algorithms. An application to selecting between six different recruitment strategies for an agricultural extension service in India demonstrates practical feasibility.

Key Points Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane. They act as sites of attachment to — and degradation of — the extracellular matrix. These structures contain actin regulators such as cortactin and neural Wiskott–Aldrich syndrome protein (N-WASP), adaptor proteins such as Tyr kinase substrate with four SH3 domains (TKS4) and Tyr kinase substrate with five SH3 domains (TKS5), and several pericellular proteases. Podosomes are found in vascular smooth muscle and endothelial cells, as well as in cells derived from monocyte lineages. Their presence correlates with migratory ability. Invadopodia are found in invasive human cancer cells. In two-dimensional culture, their presence correlates with invasive behaviour. However, in three-dimensional culture and in vivo , invadopodium-associated proteins are also required for cell growth. Podosome-associated proteins have been implicated in human developmental and immune disorders, and dysregulation of podosome formation is associated with atherosclerosis. Small-molecule regulation of podosomes and invadopodia might represent a new therapeutic strategy to treat several diseases. Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane of metazoan cells that represent sites of attachment to — and degradation of — the extracellular matrix. Progress has been made in our understanding of the regulation and function of these structures, and their role in human disease. Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane of metazoan cells that represent sites of attachment to — and degradation of — the extracellular matrix. The key proteins in these structures include the actin regulators cortactin and neural Wiskott–Aldrich syndrome protein (N-WASP), the adaptor proteins Tyr kinase substrate with four SH3 domains (TKS4) and Tyr kinase substrate with five SH3 domains (TKS5), and the metalloprotease membrane type 1 matrix metalloprotease (MT1MMP; also known as MMP14). Many cell types can produce these structures, including invasive cancer cells, vascular smooth muscle and endothelial cells, and immune cells such as macrophages and dendritic cells. Recently, progress has been made in our understanding of the regulatory and functional aspects of podosome and invadopodium biology and their role in human disease.

Small intestinal mononuclear cells that express CX3CR1 (CX3CR1 + cells) regulate immune responses 1 – 5 . CX3CR1 + cells take up luminal antigens by protruding their dendrites into the lumen 1 – 4 , 6 . However, it remains unclear how dendrite protrusion by CX3CR1 + cells is induced in the intestine. Here we show in mice that the bacterial metabolites pyruvic acid and lactic acid induce dendrite protrusion via GPR31 in CX3CR1 + cells. Mice that lack GPR31, which was highly and selectively expressed in intestinal CX3CR1 + cells, showed defective dendrite protrusions of CX3CR1 + cells in the small intestine. A methanol-soluble fraction of the small intestinal contents of specific-pathogen-free mice, but not germ-free mice, induced dendrite extension of intestinal CX3CR1 + cells in vitro. We purified a GPR31-activating fraction, and identified lactic acid. Both lactic acid and pyruvic acid induced dendrite extension of CX3CR1 + cells of wild-type mice, but not of Gpr31b −/− mice. Oral administration of lactate and pyruvate enhanced dendrite protrusion of CX3CR1 + cells in the small intestine of wild-type mice, but not in that of Gpr31b −/− mice. Furthermore, wild-type mice treated with lactate or pyruvate showed an enhanced immune response and high resistance to intestinal Salmonella infection. These findings demonstrate that lactate and pyruvate, which are produced in the intestinal lumen in a bacteria-dependent manner, contribute to enhanced immune responses by inducing GPR31-mediated dendrite protrusion of intestinal CX3CR1 + cells. In the mouse intestine, pyruvate and lactate produced from bacterial metabolites enhance immune responses through inducing dendrite protrusion, mediated by GPR31, of small intestinal mononuclear cells that express CX3CR1.

In this paper, we study matrix functions of bounded type from the viewpoint of describing an interplay between function theory and operator theory. We first establish a criterion on the coprime-ness of two singular inner functions and obtain several properties of the Douglas-Shapiro-Shields factorizations of matrix functions of bounded type. We propose a new notion of tensored-scalar singularity, and then answer questions on Hankel operators with matrix-valued bounded type symbols. We also examine an interpolation problem related to a certain functional equation on matrix functions of bounded type; this can be seen as an extension of the classical Hermite-Fejér Interpolation Problem for matrix rational functions. We then extend the

Liquid chromatography coupled with high-resolution mass spectrometry (LC–HRMS) has become a workhorse in global metabolomics studies with growing applications across biomedical and environmental sciences. However, outstanding bioinformatics challenges in terms of data processing, statistical analysis and functional interpretation remain critical barriers to the wider adoption of this technology. To help the user community overcome these barriers, we have made major updates to the well-established MetaboAnalyst platform (www.metaboanalyst.ca). This protocol extends the previous 2011 Nature Protocol by providing stepwise instructions on how to use MetaboAnalyst 5.0 to: optimize parameters for LC–HRMS spectra processing; obtain functional insights from peak list data; integrate metabolomics data with transcriptomics data or combine multiple metabolomics datasets; conduct exploratory statistical analysis with complex metadata. Parameter optimization may take ~2 h to complete depending on the server load, and the remaining three stages may be executed in ~60 min.LC–HRMS is used for metabolomics studies in the biomedical and environmental sciences. MetaboAnalyst (metaboanalyst.ca) can be used to address challenges in data processing, statistical analysis, functional interpretation and multi-omics integration.

Background: FSCN1 and matrix metalloproteinase 14 (MMP14) are both invadopodia-related proteins. We herein elucidate the tumourigenicity of these proteins and identify novel therapeutic agents in esophageal squamous cell carcinoma (ESCC). Methods: FSCN1 and MMP14 were evaluated by immunohistochemistry and quantitative PCR, and microRNA (miR)-133a was also evaluated by PCR in surgical ESCC specimens. The roles of FSCN1 , MMP14 and miR-133a were established in ESCC cells. Results: The expression of FSCN1 or MMP14 was an independent poor prognostic factor according to a multivariate analysis of immunohistochemistry, and their co-expression correlated with the poorest overall survival (OS) out of all the examined factors. Additionally, their mRNAs significantly correlated and both inversely correlated with miR-133a in surgical specimens. Transfection of a miR-133a mimic decreased the mRNA and protein levels of both FSCN1 and MMP14 in ESCC cells. The knockdown of FSCN1 or MMP14 and transfection of a miR-133a mimic inhibited the proliferation and invasion of ESCC cells. Patients with a lower miR-133a expression have a significantly poorer OS than those with a higher expression. Conclusion: The combined expression of FSCN1 and MMP14 is associated with a poor prognosis, and miR-133a, which regulates their mRNAs, can serve as a strong tumour suppressor of ESCC.