Previous research on supply risk management mainly focuses on the general risk management process based on case studies. In this study, we explore supply risk management via the relational approach ...in the Chinese business environment (i.e., guanxi) from the buying firm's perspective. We develop a theoretical model grounded in the social capital theory. Theorizing from the three forms of social capital (i.e., obligation, expectation, and trustworthiness; information channel; and norms and effective sanctions), we hypothesize that when a buying firm faces supply risk, it tends to form guanxi networks with its key supplier to reduce risk. We collect data to test the model by surveying manufacturing firms in Hong Kong and apply structural equation modeling to analyze the survey data. The research findings show that purchasing firms form guanxi networks with their key suppliers when they perceive supply risk. We also find that with guanxi development between the buyer and the supplier, both communication and supplier trust are improved, which in turn are positively related to supplier performance. This research contributes to theory by identifying the role of guanxi in supply risk management and to practice by providing insights to purchasing professionals that guide their effort in managing supply risk.
The structural flexibility of RNA underlies fundamental biological processes, but there are no methods for exploring the multiple conformations adopted by RNAs in vivo. We developed cross-linking of ...matched RNAs and deep sequencing (COMRADES) for in-depth RNA conformation capture, and a pipeline for the retrieval of RNA structural ensembles. Using COMRADES, we determined the architecture of the Zika virus RNA genome inside cells, and identified multiple site-specific interactions with human noncoding RNAs.
Lysosomes serve as the degradation hubs for macroautophagic/autophagic and endocytic components, thus maintaining cellular homeostasis essential for neuronal survival and function. LAMP1 (lysosomal ...associated membrane protein 1) and LAMP2 are distributed among autophagic and endolysosomal organelles. Despite widespread distribution, LAMP1 is routinely used as a lysosome marker and LAMP1-positive organelles are often referred to as lysosomal compartments. By applying immuno-electron microscopy (iTEM) and confocal imaging combined with Airyscan microscopy, we expand on the limited literature to provide a comprehensive and quantitative analysis of LAMP1 distribution in various autophagic and endolysosomal organelles in neurons. Our study demonstrates that a significant portion of LAMP1-labeled organelles lack major lysosomal hydrolases. BSA-gold pulse-chase assay further shows heterogeneous degradative capacities of LAMP1-labled organelles. In addition, LAMP1 intensity is not a sensitive readout to assess lysosomal deficits in familial amyotrophic lateral sclerosis-linked motor neurons in vivo. Our study thus calls for caution when interpreting LAMP1-labeled organelles in the nervous system where LAMP1 intensity, trafficking, and distribution do not necessarily represent degradative lysosomes or autolysosomes under physiological and pathological conditions.
Abbreviations: ALS: amyotrophic lateral sclerosis; BSA: bovine serum albumin; DRG: dorsal root ganglion; IGF2R/CI-M6PR: insulin like growth factor 2 receptor; iTEM: immuno-transmission electron microscopy; LAMP1/2: lysosomal associated membrane protein 1/2; P80: postnatal day 80; sMNs: spinal motor neurons
It is a central tenet of cochlear neurobiology that mammalian ears rely on a local, mechanical amplification process for their high sensitivity and sharp frequency selectivity. While it is generally ...agreed that outer hair cells provide the amplification, two mechanisms have been proposed: stereociliary motility and somatic motility. The latter is driven by the motor protein prestin. Electrophysiological phenotyping of a prestin knockout mouse intimated that somatic motility is the amplifier. However, outer hair cells of knockout mice have significantly altered mechanical properties, making this mouse model unsatisfactory. Here, we study a mouse model without alteration to outer hair cell and organ of Corti mechanics or to mechanoelectric transduction, but with diminished prestin function. These animals have knockout-like behavior, demonstrating that prestin-based electromotility is required for cochlear amplification.
The exact identity of castrate-resistant (CR) cells and their relation to CR prostate cancer (CRPC) is unresolved. We use single-cell gene profiling to analyze the molecular heterogeneity in basal ...and luminal compartments. Within the luminal compartment, we identify a subset of cells intrinsically resistant to castration with a bi-lineage gene expression pattern. We discover LY6D as a marker of CR prostate progenitors with multipotent differentiation and enriched organoid-forming capacity. Lineage tracing further reveals that LY6D+ CR luminal cells can produce LY6D− luminal cells. In contrast, in luminal cells lacking PTEN, LY6D+ cells predominantly give rise to LY6D+ tumor cells, contributing to high-grade PIN lesions. Gene expression analyses in patients’ biopsies indicate that LY6D expression correlates with early disease progression, including progression to CRPC. Our studies thus identify a subpopulation of luminal progenitors characterized by LY6D expression and intrinsic castration resistance. LY6D may serve as a prognostic maker for advanced prostate cancer.
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•Single-cell analysis identifies a highly heterogeneous luminal compartment•LY6D marks luminal cells that are resistant to castration with bi-lineage capacity•LY6D correlates with prostate cancer development from luminal lineage•LY6D expression in human prostate cancer correlates with early disease progression
To address the identity of castration-resistant prostate cells in vivo, Barros-Silva et al. coupled single-cell analysis with organoid culture and in situ lineage tracing. They identify LY6D as a progenitor marker that liaises intrinsically castration-resistant luminal cells and castration-resistant prostate tumor growth.
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