Region-specific and activity-dependent regulation of SVZ neurogenesis and recovery after stroke.

Stroke is the leading cause of adult disability. Neurogenesis after stroke is associated with repair; however, the mechanisms regulating poststroke neurogenesis and its functional effect remain unclear. Here, we investigate multiple mechanistic routes of induced neurogenesis in the poststroke brain, using both a forelimb overuse manipulation that models a clinical neurorehabilitation paradigm, as well as local manipulation of cellular activity in the peri-infarct cortex. Increased activity in the forelimb peri-infarct cortex via either modulation drives increased subventricular zone (SVZ) progenitor proliferation, migration, and neuronal maturation in peri-infarct cortex. This effect is sensitive to competition from neighboring brain regions. By using orthogonal tract tracing and rabies virus approaches in transgenic SVZ-lineage-tracing mice, SVZ-derived neurons synaptically integrate into the peri-infarct cortex; these effects are enhanced with forelimb overuse. Synaptic transmission from these newborn SVZ-derived neurons is critical for spontaneous recovery after stroke, as tetanus neurotoxin silencing specifically of the SVZ-derived neurons disrupts the formation of these synaptic connections and hinders functional recovery after stroke. SVZ-derived neurogenesis after stroke is activity-dependent, region-specific, and sensitive to modulation, and the synaptic connections formed by these newborn cells are functionally critical for poststroke recovery

The pathogenic role of the renal proximal tubular cell in diabetic nephropathy

Abstract A growing body of evidence indicates that the renal proximal tubular epithelial cell (PTEC) plays an important role in the pathogenesis of diabetic nephropathy (DN). Microalbuminuria that intensifies over time to overt proteinuria, a hallmark of DN, is already known to activate the PTEC to induce tubulointerstitial inflammation. In addition to proteins, a number of diabetic substrates including high glucose per se, advanced glycation end-products and their carbonyl intermediates, angiotensin II, and ultrafiltered growth factors activate a number of signaling pathways including nuclear factor kappa B, protein kinase C, extracellular signal-regulated kinase 1/2, p38, signal transducer and activator of transcription-1 and the generation of reactive oxygen species, to culminate in tubular cell hypertrophy and the accumulation in the interstitium of a repertoire of chemokines, cytokines, growth factors and adhesion molecules capable of orchestrating further inflammation and fibrosis. More recently, the kallikreinkinin system (KKS) and toll-like receptors (TLRs) in PTECs have been implicated in this process. While in vitro data suggest that the KKS contributes to the progression of DN, there are conflicting in vivo results on its precise role, which may in part be strain-dependent. On the other hand, there are both in vitro and in vivo data to suggest a role for both TLR2 and TLR4 in DN. In this review, we offer a critical appraisal of the events linking the participation of the PTEC to the pathogenesis of DN, which we believe may be collectively termed diabetic tubulopathy

A Nanophotonic Structure Containing Living Photosynthetic Bacteria

Photosynthetic organisms rely on a series of self-assembled nanostructures with tuned electronic energy levels in order to transport energy from where it is collected by photon absorption, to reaction centers where the energy is used to drive chemical reactions. In the photosynthetic bacteria Chlorobaculum tepidum, a member of the green sulfur bacteria family, light is absorbed by large antenna complexes called chlorosomes to create an exciton. The exciton is transferred to a protein baseplate attached to the chlorosome, before migrating through the Fenna-Matthews-Olson complex to the reaction center. Here, it is shown that by placing living Chlorobaculum tepidum bacteria within a photonic microcavity, the strong exciton-photon coupling regime between a confined cavity mode and exciton states of the chlorosome can be accessed, whereby a coherent exchange of energy between the bacteria and cavity mode results in the formation of polariton states. The polaritons have energy distinct from that of the exciton which can be tuned by modifying the energy of the optical modes of the microcavity. It is believed that this is the first demonstration of the modification of energy levels within living biological systems using a photonic structure

Impoundment increases methane emissions in Phragmites‐invaded coastal wetlands

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sanders‐DeMott, R., Eagle, M., Kroeger, K., Wang, F., Brooks, T., Suttles, J., Nick, S., Mann, A., & Tang, J. Impoundment increases methane emissions in Phragmites‐invaded coastal wetlands. Global Change Biology, 28(15), (2022): 4539– 4557. https://doi.org/10.1111/gcb.16217.Saline tidal wetlands are important sites of carbon sequestration and produce negligible methane (CH4) emissions due to regular inundation with sulfate-rich seawater. Yet, widespread management of coastal hydrology has restricted tidal exchange in vast areas of coastal wetlands. These ecosystems often undergo impoundment and freshening, which in turn cause vegetation shifts like invasion by Phragmites, that affect ecosystem carbon balance. Understanding controls and scaling of carbon exchange in these understudied ecosystems is critical for informing climate consequences of blue carbon restoration and/or management interventions. Here, we (1) examine how carbon fluxes vary across a salinity gradient (4–25 psu) in impounded and natural, tidally unrestricted Phragmites wetlands using static chambers and (2) probe drivers of carbon fluxes within an impounded coastal wetland using eddy covariance at the Herring River in Wellfleet, MA, United States. Freshening across the salinity gradient led to a 50-fold increase in CH4 emissions, but effects on carbon dioxide (CO2) were less pronounced with uptake generally enhanced in the fresher, impounded sites. The impounded wetland experienced little variation in water-table depth or salinity during the growing season and was a strong CO2 sink of −352 g CO2-C m−2 year−1 offset by CH4 emission of 11.4 g CH4-C m−2 year−1. Growing season CH4 flux was driven primarily by temperature. Methane flux exhibited a diurnal cycle with a night-time minimum that was not reflected in opaque chamber measurements. Therefore, we suggest accounting for the diurnal cycle of CH4 in Phragmites, for example by applying a scaling factor developed here of ~0.6 to mid-day chamber measurements. Taken together, these results suggest that although freshened, impounded wetlands can be strong carbon sinks, enhanced CH4 emission with freshening reduces net radiative balance. Restoration of tidal flow to impounded ecosystems could limit CH4 production and enhance their climate regulating benefits.This project was supported by USGS-NPS Natural Resources Preservation Program #2021-07, U.S. Geological Survey Coastal & Marine Hazards and Resources Program and the USGS Land Change Science Program's LandCarbon program, and NOAA National Estuarine Research Reserve Science Collaborative NA14NOS4190145. R Sanders-DeMott was supported by a USGS Mendenhall Fellowship and partnership with Restore America's Estuaries

Gut microbiome variation modulates the effects of dietary fiber on host metabolism

Background: There is general consensus that consumption of dietary fermentable fiber improves cardiometabolic health, in part by promoting mutualistic microbes and by increasing production of beneficial metabolites in the distal gut. However, human studies have reported variations in the observed benefits among individuals consuming the same fiber. Several factors likely contribute to this variation, including host genetic and gut microbial differences. We hypothesized that gut microbial metabolism of dietary fiber represents an important and differential factor that modulates how dietary fiber impacts the host. Results: We examined genetically identical gnotobiotic mice harboring two distinct complex gut microbial communities and exposed to four isocaloric diets, each containing different fibers: (i) cellulose, (ii) inulin, (iii) pectin, (iv) a mix of 5 fermentable fibers (assorted fiber). Gut microbiome analysis showed that each transplanted community preserved a core of common taxa across diets that differentiated it from the other community, but there were variations in richness and bacterial taxa abundance within each community among the different diet treatments. Host epigenetic, transcriptional, and metabolomic analyses revealed diet-directed differences between animals colonized with the two communities, including variation in amino acids and lipid pathways that were associated with divergent health outcomes. Conclusion: This study demonstrates that interindividual variation in the gut microbiome is causally linked to differential effects of dietary fiber on host metabolic phenotypes and suggests that a one-fits-all fiber supplementation approach to promote health is unlikely to elicit consistent effects across individuals. Overall, the presented results underscore the importance of microbe-diet interactions on host metabolism and suggest that gut microbes modulate dietary fiber efficacy. [MediaObject not available: see fulltext.]Fil: Murga Garrido, Sofia M.. Universidad Nacional Autónoma de México; México. University of Wisconsin; Estados UnidosFil: Hong, Qilin. University of Wisconsin; Estados UnidosFil: Cross, Tzu Wen L.. University of Wisconsin; Estados Unidos. Purdue University; Estados UnidosFil: Hutchison, Evan R.. University of Wisconsin; Estados UnidosFil: Han, Jessica. Wisconsin Institute for Discovery; Estados UnidosFil: Thomas, Sydney P.. Wisconsin Institute for Discovery; Estados UnidosFil: Vivas, Eugenio I.. University of Wisconsin; Estados UnidosFil: Denu, John. Wisconsin Institute for Discovery; Estados UnidosFil: Ceschin, Danilo Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Tang, Zheng Zheng. University of Wisconsin; Estados Unidos. Wisconsin Institute for Discovery; Estados UnidosFil: Rey, Federico E.. University of Wisconsin; Estados Unido

Large Between-Patient Variability in eGFR Decline Before Clinical Trial Enrollment and Impact on Atrasentan's Efficacy - A Post-Hoc Analysis From the SONAR Trial

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