Purpose: Management of pregnancy and delivery in women with lower urinary tract reconstruction is challenging and the currently available literature is insufficient to guide clinical practice. We report pregnancy and delivery outcomes in this specific population.
Materials And Methods: We conducted a national multicenter retrospective study (16 centers) including 68 women with 96 deliveries between 1998 and 2019.
The folding of RNA into a wide range of structures is essential for its diverse biological functions from enzymatic catalysis to ligand binding and gene regulation. The unfolding and refolding of individual RNA molecules can be probed by single-molecule force spectroscopy (SMFS), enabling detailed characterization of the conformational dynamics of the molecule as well as the free-energy landscape underlying folding. Historically, high-precision SMFS studies of RNA have been limited to custom-built optical traps.
View Article and Find Full Text PDFSingle-molecule force spectroscopy (SMFS) is a powerful technique to characterize the energy landscape of individual proteins, the mechanical properties of nucleic acids, and the strength of receptor-ligand interactions. Atomic force microscopy (AFM)-based SMFS benefits from ongoing progress in improving the precision and stability of cantilevers and the AFM itself. Underappreciated is that the accuracy of such AFM studies remains hindered by inadvertently stretching molecules at an angle while measuring only the vertical component of the force and extension, degrading both measurements.
View Article and Find Full Text PDFQuantifying the energy landscape underlying protein-ligand interactions leads to an enhanced understanding of molecular recognition. A powerful yet accessible single-molecule technique is atomic force microscopy (AFM)-based force spectroscopy, which generally yields the zero-force dissociation rate constant (k ) and the distance to the transition state (Δx ). Here, we introduce an enhanced AFM assay and apply it to probe the computationally designed protein DIG10.
View Article and Find Full Text PDFAtomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is a powerful yet accessible means to characterize mechanical properties of biomolecules. Historically, accessibility relies upon the nonspecific adhesion of biomolecules to a surface and a cantilever and, for proteins, the integration of the target protein into a polyprotein. However, this assay results in a low yield of high-quality data, defined as the complete unfolding of the polyprotein.
View Article and Find Full Text PDFA diverse array of G protein-coupled receptors (GPCRs) is implicated in the modulation of nociception. The efficacy and potency of several GPCR agonists change as a consequence of peripheral inflammatory injury. Whether these changes reflect alterations in expression of the G proteins themselves is not known.
View Article and Find Full Text PDFInjury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy.
View Article and Find Full Text PDFThis study examined whether peripheral inflammatory injury increases the levels or changes the disposition of substance P (SubP) in the rostral ventromedial medulla (RVM), which serves as a central relay in bulbospinal pathways of pain modulation. Enzyme immunoassay and reverse transcriptase quantitative polymerase chain reaction were used to measure SubP protein and transcript, respectively, in tissue homogenates prepared from the RVM and the periaqueductal gray (PAG) and cuneiform nuclei of rats that had received an intraplantar injection of saline or complete Freund's adjuvant (CFA). Matrix-Assisted Laser Desorption/Ionization Time of Flight analysis confirmed that the RVM does not contain hemokinin-1 (HK-1), which can confound measurements of SubP because it is recognized equally well by commercial antibodies for SubP.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
September 2015
Thin-shell instability is one process which can generate entangled structures in astrophysical plasma on collisional (fluid) scales. It is driven by a spatially varying imbalance between the ram pressure of the inflowing upstream plasma and the downstream's thermal pressure at a nonplanar shock. Here we show by means of a particle-in-cell simulation that an analog process can destabilize a thin shell formed by two interpenetrating, unmagnetized, and collisionless plasma clouds.
View Article and Find Full Text PDFAtomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is widely used to mechanically measure the folding and unfolding of proteins. However, the temporal resolution of a standard commercial cantilever is 50-1000 μs, masking rapid transitions and short-lived intermediates. Recently, SMFS with 0.
View Article and Find Full Text PDFAdvanced optical traps can probe single molecules with Ångstrom-scale precision, but drift limits the utility of these instruments. To achieve Å-scale stability, a differential measurement scheme between a pair of laser foci was introduced that substantially exceeds the inherent mechanical stability of various types of microscopes at room temperature. By using lock-in detection to measure both lasers with a single quadrant photodiode, we enhanced the differential stability of this optical reference frame and thereby stabilized an optical-trapping microscope to 0.
View Article and Find Full Text PDFIntroduction: Bladder augmentation is commonly used in neurological and other congenital anomalies of the lower urinary tract. In pregnant women, this reconstructive surgery may affect pregnancy and delivery. The obstetrical consequences of these urological procedures are scarcely reported in literature.
View Article and Find Full Text PDFBackground: Real-time quantitative PCR (qPCR) is a technique frequently used to measure changes in mRNA expression. To ensure validity of experimental findings, it is important to normalize the qPCR data to reference genes that are stable and unaffected by the experimental treatment to correct for variability among samples. Unlike in some models of neuropathic pain, reference genes for models of inflammatory injury have not been validated.
View Article and Find Full Text PDFIntroduction: Acid-sensing ion channel 3 (ASIC3) is expressed in synoviocytes, activated by decreases in pH, and reduces inflammation in animal models of inflammatory arthritis. The purpose of the current study was to characterize potential mechanisms underlying the control of inflammation by ASIC3 in fibroblast-like synoviocytes (FLS).
Methods: Experiments were performed in cultured FLS from wild-type (WT) and ASIC3-/- mice, ASIC1-/- mice, and people with rheumatoid arthritis.
This study examined possible mechanisms by which Substance P (Sub P) assumes a pronociceptive role in the rostral ventromedial medulla (RVM) under conditions of peripheral inflammatory injury, in this case produced by intraplantar (ipl) injection of complete Freund's adjuvant (CFA). In saline- and CFA-treated rats, neurokinin-1 receptor (NK1R) immunoreactivity was localized to neurons in the RVM. Four days after ipl injection of CFA, the number of NK1R-immunoreactive neurons in the RVM was increased by 30%, and there was a concomitant increase in NK1R-immunoreactive processes in CFA-treated rats.
View Article and Find Full Text PDFWhile traditional models of protein adsorption focus primarily on direct protein-surface interactions, recent findings suggest that protein-protein interactions may play a central role. Using high-throughput intermolecular resonance energy transfer (RET) tracking, we directly observed dynamic, protein-protein associations of bovine serum albumin on polyethylene glycol modified surfaces. The associations were heterogeneous and reversible, and associating molecules resided on the surface for longer times.
View Article and Find Full Text PDFObjective: Through its location on nociceptors, acid-sensing ion channel 3 (ASIC-3) is activated by decreases in pH and plays a significant role in musculoskeletal pain. We recently showed that decreases in pH activate ASIC-3 located on fibroblast-like synoviocytes (FLS), which are key cells in the inflammatory process. The purpose of this study was to test whether ASIC-3-deficient mice with arthritis have altered inflammation and pain relative to controls.
View Article and Find Full Text PDFThe interactions between adsorbate molecules and hydrophobic surfaces are of significant interest due to their importance in a variety of biological and separation processes. However, it is challenging to extrapolate macroscopic ensemble-averaged force measurements to molecular-level phenomena. Using total internal reflection fluorescence microscopy to image individual molecules at hydrophobic solid-aqueous interfaces, we directly observed dynamic behavior associated with the interactions between fluorescently labeled dodecanoic acid (our probe molecules) and self-assembled monolayers (SAM) comprising n-alkyltriethoxysilanes with systematically increasing chain length (from n = 4-18).
View Article and Find Full Text PDFThe "soft" (i.e., noncovalent) interactions between molecules and surfaces are complex and highly varied (e.
View Article and Find Full Text PDFInflammatory thermal hyperalgesia is principally mediated through transient receptor potential vanilloid 1 (TRPV1) channels, as demonstrated by prior studies using models of cutaneous inflammation. Muscle pain is significantly different from cutaneous pain, and the involvement of TRPV1 in hyperalgesia induced by muscle inflammation is unknown. We tested whether TRPV1 contributes to the development of mechanical and heat hypersensitivity of the paw in TRPV1(-/-) mice after muscle inflammation.
View Article and Find Full Text PDFHigh throughput single molecule tracking methods were developed to perform quantitative analyses of rare molecular populations. An optimization strategy for single molecule tracking at interfaces is described that allowed tracking of ~10(6) unique trajectories. These large statistical datasets were analyzed in order to identify and characterize distinct molecular populations based on their characteristic dynamic behavior (residence time or surface diffusion) and/or their spatial distribution.
View Article and Find Full Text PDFBy directly observing molecular trajectories on a chemically heterogeneous surface, we have identified two distinct modes of diffusion involving (1) displacements within isolated surface islands (crawling mode), and (2) displacements where a molecule desorbs from an island, diffuses through the adjacent liquid phase, and readsorbs on another island (flying mode). The diffusion coefficients corresponding to these two modes differ by an order of magnitude, and both modes are also observed on chemically homogeneous surfaces. Comparison with previous results suggested that desorption-mediated diffusion is the primary transport mechanism in self-assembled monolayer formation.
View Article and Find Full Text PDFThe surface characterization of 'soft' materials presents a significant scientific challenge, particularly under 'wet' in situ conditions where a wide variety of non-covalent interactions may be relevant. Here we introduce a new chemical imaging method, MAPT (mapping using accumulated probe trajectories) that generates images of surface interactions by distributing different aspects of molecular probe trajectories into distinct locations and then combining many trajectories to generate spatial maps. The maps are super-resolution in nature, because they are accumulated from highly localized single-molecule observations.
View Article and Find Full Text PDFAcid-sensing ion channels (ASICs) are activated by acidic pH and may play a significant role in the development of hyperalgesia. Earlier studies show ASIC3 is important for induction of hyperalgesia after muscle insult using ASIC3-/- mice. ASIC3-/- mice lack ASIC3 throughout the body, and the distribution and composition of ASICs could be different from wild-type mice.
View Article and Find Full Text PDFFluorescence recovery after photobleaching was used to characterize the diffusion of fluorescently labeled phospholipids at the oil/water interface for oil viscosities that varied over four orders of magnitude. Measurements were performed over a range of surface concentrations corresponding to molecular areas of 40-130 A(2)/molecule. As expected, the interfacial diffusion coefficient increased with molecular area, saturating at an area of approximately 100 A(2)/molecule.
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