Project description:We report the application of single cell RNA-seq for transcript profiling in bladder tissue from Interstitial cystitis/bladder pain syndrome (IC/BPS) with Hunner lesions and without Hunner lesions and normal tissue.
Project description:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating pain disorder of the bladder and urinary tract with poorly understood etiology. A definitive diagnosis of IC/BPS can be challenging because many symptoms of IC/BPS are shared with other urological disorders. An analysis of urine presents an attractive and non-invasive resource for monitoring and diagnosing IC/BPS. Here, a non-targeted LC-MS and LC-MS/MS-based peptidomics analysis of urine samples collected from IC/BPS patients were compared to urine samples from asymptomatic controls.
Project description:Interstitial cystitis (IC) and bladder pain syndrome are terms used to describe a heterogenous chronic pelvic and bladder pain disorder of unknown etiology. The goal of this pilot study was to determine if gene expression profiling of bladder biopsy tissue from patients experiencing symptoms could be used to separate the patients based on some clinical parameter. Gene expression profiles in bladder biopsy tissue from patients with: (1) low bladder capacity (defined here as <400 ml upon hydordistension), (2) normal capacity (M-bM-^IM-%400 ml), and (3) controls were compared. Gene expression profiles from low bladder capacity tissues differed significantly from normal capacity and control tissue, suggesting gene expression profiling may be a useful tool for better understanding IC disease pathophysiology.
Project description:Interstitial cystitis (IC) is a progressive chronic bladder disease with an increasing incidence. Today, IC is diagnosed by subjective symptoms in combination with cystoscopic and histologic evidence. The ultimate goal is the development of a diagnostic assay for IC on a molecular level. A comparative gene expression profile of bladder biopsies from patients with IC and control patients identified candidate marker genes for IC. Experiment Overall Design: Five IC patients and six control patients ('healthy') have been selected for the study. All IC patients had Hunner's ulcers and, with the exception of one person, also glomerulations, whereas the control group did not show these cystoscopic findings. From each IC patient two biopsies have been taken, one from an ulcerated area of the bladder ('ulcus'), and one from an area that macroscopically looked 'normal', 'not-inflamed' or not hyperemic ('ni'). One 'ni' sample has been excluded from the study because it had an expression pattern similar to the healthy controls.
Project description:Interstitial cystitis (IC), a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. The ultimate goal is the development of a diagnostic assay for IC on a molecular level. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed. Candidate marker genes for ulcerative IC were identified.
Project description:Interstitial cystitis (IC) and bladder pain syndrome are terms used to describe a heterogenous chronic pelvic and bladder pain disorder of unknown etiology. The goal of this pilot study was to determine if gene expression profiling of bladder biopsy tissue from patients experiencing symptoms could be used to separate the patients based on some clinical parameter.
Project description:Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a clinical condition that manifests as a sensory hypersensitivity of unknown cause and is characterized by urinary frequency, bladder discomfort, and pelvic pain. In the present volatolomic study, we have analyzed the VOCs unique to urine specimens obtained from interstitial cystitis patients, in compassion to healthy controls.This is the novel finding from comprehensive and unbiased metabolomics analysis that urinary menthol is decreased in urine specimens from IC patients, and that the reduced menthol level in IC is potentially linked to the chronic inflammation, which is often observed in IC patients
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
Project description:Major gaps remain in our knowledge of the early history of Homo sapiens in Wallacea. By 70-60 thousand years ago (ka), modern humans appear to have entered this distinct biogeographical zone between continental Asia and Australia. Despite this, there are relatively few Late Pleistocene sites attributed to our species in Wallacea. H. sapiens fossil remains are also rare. Previously, only one island in Wallacea (Alor in the southeastern part of the archipelago) had yielded skeletal evidence for pre-Holocene modern humans. Here we report on the first Pleistocene human skeletal remains from the largest Wallacean island, Sulawesi. The recovered elements consist of a nearly complete palate and frontal process of a modern human right maxilla excavated from Leang Bulu Bettue in the southwestern peninsula of the island. Dated by several different methods to between 25 and 16 ka, the maxilla belongs to an elderly individual of unknown age and sex, with small teeth (only M1 to M3 are extant) that exhibit severe occlusal wear and related dental pathologies. The dental wear pattern is unusual. This fragmentary specimen, though largely undiagnostic with regards to morphological affinity, provides the only direct insight we currently have from the fossil record into the identity of the Late Pleistocene people of Sulawesi.