Removal of urothelium affects bladder contractility and release of ATP but not release of NO in rat urinary bladder

<p>Abstract</p> <p>Background</p> <p>The objective of our work was to investigate both the contractile function and the release of ATP and NO from strips of bladder tissue after removal of the urothelium.</p> <p>Methods</p> <p>The method of removal was a gentle swabbing motion rather than a sharp surgical cutting to separate the urothelium from the smooth muscle. The contractile response and ATP and NO release were measured in intact as well as on swabbed preparations. The removal of the urothelial layer was affirmed microscopically.</p> <p>Results</p> <p>After the swabbing, the smaller contractions were evoked by electrical as well as by chemical stimulation (50 μM carbachol or 50 μM α, β meATP). Electrical stimulation, carbachol and substance P (5 μM) evoked lower release of ATP in the swabbed strips than in intact strips. Although release of NO evoked by electrical stimulation or substance P was not changed, release of NO evoked by carbachol was significantly less in the swabbed preparations.</p> <p>Conclusion</p> <p>Since swabbing removes only the urothelium, the presence of the suburothelial layer may explain the difference between our findings and those of others who found an increase in contractility. Evoked release of ATP is reduced in swabbed strips, indicating that ATP derives solely from the urothelium. On the other hand, electrical stimulation and substance P evoke identical degrees of NO release in both intact and swabbed preparations, suggesting that NO can be released from the suburothelium. Conversely, carbachol-induced release of NO is lower in swabbed strips, implying that the cholinergic receptors (muscarinic or nicotinic) are located in the upper layer of the urothelium.</p

Altered Bladder-Related Brain Network in Multiple Sclerosis Women With Voiding Dysfunction

Objectives: A number of neuro-urology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions in order to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamics (UDS)/fMRI. Materials and Methods: Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥ 6 months and symptomatic voiding phase Neurogenic Lower Urinary Tract Dysfunction (NLUTD) underwent UDS/fMRI evaluation with a task of bladder filling/emptying that was repeated three to five times. We quantitatively compared their FC within 17 bladder-related brain regions during two urodynamic phases: ‘strong desire to void’ and ‘(attempt at) voiding initiation’. Results: At ‘strong desire to void’, the healthy group showed significantly stronger FC in regions involved in bladder filling and suppression of voiding compared to the patient group. These regions included the bilateral anterior cingulate cortex, right supplementary motor area, and right middle frontal gyrus. During ‘(attempt at) voiding initiation’, healthy subjects exhibited stronger FC in the right inferior frontal gyrus compared to MS patients. Conclusion: Our study offers a new way to identify alterations in the neural mechanisms underlying NLUTD and provides potential targets for clinical interventions (such as cortical neuromodulation) aimed at restoring bladder functions in MS patients

Infrared Galaxies in the Field of the Massive Cluster Abell S1063: Discovery of a Luminous Kiloparsec-Sized HII Region in a Gravitationally Lensed IR-Luminous Galaxy at z=0.6z=0.6

Using the Spitzer Space Telescope and Herschel Space Observatory, we have conducted a survey of infrared galaxies in the field of the galaxy cluster Abell S1063 (AS1063) at $z=0.347$, which is one of the most massive clusters known and a target of the HST CLASH and Frontier-Field surveys. The Spitzer/MIPS 24 $\mu$m and Herschel/PACS & SPIRE images revealed that the core of AS1063 is surprisingly devoid of infrared sources, showing only a few detectable sources within the central r$\sim1^{\prime}$. There is, however, one particularly bright source (2.3 mJy at 24 $\mu$m; 106 mJy at 160 $\mu$m), which corresponds to a background galaxy at $z=0.61$. The modest magnification factor (4.0$\times$) implies that this galaxy is intrinsically IR-luminous (L$_{\rm IR}=3.1\times10^{11}\ \rm L_{\odot}$). What is particularly interesting about this galaxy is that HST optical/near-infrared images show a remarkably bright and large (1 kpc) clump at one edge of the disk. Our follow-up optical/near-infrared spectroscopy shows Balmer (H$\alpha$-H8) and forbidden emission from this clump ([OII] $\lambda$3727, [OIII] $\lambda\lambda$4959,5007, [NII] $\lambda\lambda$6548,6583), indicating that it is a HII region. The HII region appears to have formed in-situ, as kinematically it is part of a rotating disk, and there is no evidence of nearby interacting galaxies. With an extinction correction of A$_{\rm V}=1.5$ mag, the star formation rate of this giant HII region is $\sim$10 M$_{\odot}$ yr$^{-1}$, which is exceptionally large, even for high redshift HII regions. Such a large and luminous HII region is often seen at $z\sim2$ but quite rare in the nearby Universe.Comment: Accepted for publication in the Astrophysical Journal. 29 pages, 15 figure

The role of virtual reality as adjunctive therapy to spinal cord stimulation in chronic pain: A feasible concept?

Spinal cord stimulation and virtual reality therapy are established and promising techniques, respectively, for managing chronic pain, each with its unique advantages and challenges. While each therapy has been the subject of significant research interest, the prospect of combining the two modalities to offer a synergistic effect in chronic pain therapy is still in its infancy. In this narrative review, we assess the state of the field combining virtual reality as an adjunctive therapy to spinal cord stimulation in chronic pain. We also review the broader field of virtual reality therapy for acute and chronic pain, considering evidence related to feasibility in the Canadian healthcare system from cost and patient satisfaction perspectives. While early results show promise, there are unexplored aspects of spinal cord stimulation combined with virtual reality therapy, particularly long-term effects on analgesia, anxiolysis, and implications on the effectiveness and longevity of spinal cord stimulation. The infrastructure for billing virtual reality as a consult service or therapy must also catch up if it is eventually used to supplement spinal cord stimulation for chronic pain

Identification of a Bacterial Type III Effector Family with G Protein Mimicry Functions

SummaryMany bacterial pathogens use the type III secretion system to inject “effector” proteins into host cells. Here, we report the identification of a 24 member effector protein family found in pathogens including Salmonella, Shigella, and enteropathogenic E. coli. Members of this family subvert host cell function by mimicking the signaling properties of Ras-like GTPases. The effector IpgB2 stimulates cellular responses analogous to GTP-active RhoA, whereas IpgB1 and Map function as the active forms of Rac1 and Cdc42, respectively. These effectors do not bind guanine nucleotides or have sequences corresponding the conserved GTPase domain, suggesting that they are functional but not structural mimics. However, several of these effectors harbor intracellular targeting sequences that contribute to their signaling specificities. The activities of IpgB2, IpgB1, and Map are dependent on an invariant WxxxE motif found in numerous effectors leading to the speculation that they all function by a similar molecular mechanism

Linking Animals Aloft with the Terrestrial Landscape

Despite using the aerosphere for many facets of their life, most flying animals (i.e., birds, bats, some insects) are still bound to terrestrial habitats for resting, feeding, and reproduction. Comprehensive broad-scale observations by weather surveillance radars of animals as they leave terrestrial habitats for migration or feeding flights can be used to map their terrestrial distributions either as point locations (e.g., communal roosts) or as continuous surface layers (e.g., animal densities in habitats across a landscape). We discuss some of the technical challenges to reducing measurement biases related to how radars sample the aerosphere and the flight behavior of animals. We highlight a recently developed methodological approach that precisely and quantitatively links the horizontal spatial structure of birds aloft to their terrestrial distributions and provides novel insights into avian ecology and conservation across broad landscapes. Specifically, we present case studies that (1) elucidate how migrating birds contend with crossing ecological barriers and extreme weather events, (2) identify important stopover areas and habitat use patterns of birds along their migration routes, and (3) assess waterfowl response to wetland habitat management and restoration. These studies aid our understanding of how anthropogenic modification of the terrestrial landscape (e.g., urbanization, habitat management), natural geographic features, and weather (e.g., hurricanes) can affect the terrestrial distributions of flying animals

Linking Animals Aloft with the Terrestrial Landscape

Despite using the aerosphere for many facets of their life, most flying animals (i.e., birds, bats, some insects) are still bound to terrestrial habitats for resting, feeding, and reproduction. Comprehensive broad-scale observations by weather surveillance radars of animals as they leave terrestrial habitats for migration or feeding flights can be used to map their terrestrial distributions either as point locations (e.g., communal roosts) or as continuous surface layers (e.g., animal densities in habitats across a landscape). We discuss some of the technical challenges to reducing measurement biases related to how radars sample the aerosphere and the flight behavior of animals. We highlight a recently developed methodological approach that precisely and quantitatively links the horizontal spatial structure of birds aloft to their terrestrial distributions and provides novel insights into avian ecology and conservation across broad landscapes. Specifically, we present case studies that (1) elucidate how migrating birds contend with crossing ecological barriers and extreme weather events, (2) identify important stopover areas and habitat use patterns of birds along their migration routes, and (3) assess waterfowl response to wetland habitat management and restoration. These studies aid our understanding of how anthropogenic modification of the terrestrial landscape (e.g., urbanization, habitat management), natural geographic features, and weather (e.g., hurricanes) can affect the terrestrial distributions of flying animals

Impact of climate change on African agriculture: focus on pests and diseases

According to the IPCC’s Fifth Assessment Report, changes in the climate over the last 30 years have already reduced global agricultural production by 1 – 5 % per decade relative to a baseline without climate change. In addition, recent studies indicate that even a 2 degrees increase in global temperature will affect agricultural productivity, particularly in the tropics, and this impact will rise with increases in temperature. In this context, this Info Note presents recent evidence on the implications for crops, livestock, and fisheries production, and their associated pests and diseases in Africa

Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation

Hsp90 is a highly conserved molecular chaperone that is involved in modulating a multitude of cellular processes. In this study, we identify a function for the chaperone in RNA processing and maintenance. This functionality of Hsp90 involves two recently identified interactors of the chaperone: Tah1 and Pih1/Nop17. Tah1 is a small protein containing tetratricopeptide repeats, whereas Pih1 is found to be an unstable protein. Tah1 and Pih1 bind to the essential helicases Rvb1 and Rvb2 to form the R2TP complex, which we demonstrate is required for the correct accumulation of box C/D small nucleolar ribonucleoproteins. Together with the Tah1 cofactor, Hsp90 functions to stabilize Pih1. As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions. Hsp90 and R2TP proteins are also involved in the proper accumulation of box H/ACA small nucleolar RNAs