GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics.

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10(-13), r(2) = 8.9%, β = -0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with-but is statistically distinct from-the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10(-37), r(2) = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception

Traumatic posterior urethral fistula to hip joint following gunshot injury: a case report

<p>Abstract</p> <p>Introduction</p> <p>Urinary system fistula to the hip joint is a rare complication. We report a case of delayed posterior urethral fistula to the hip joint following penetrating gunshot wound injury.</p> <p>Case presentation</p> <p>A 37-year-old Iranian Balochi male was shot with a firearm in the superior part of his right pelvis. He underwent primary closure on the same day. Ten months later, he developed urinary retention. He underwent retrograde urethrography and antegrade cystography which showed a stricture measuring 5 cm in length. There was also a history of progressive pain in the right hip joint accompanied by low grade fever which started 2 months after the initial injury. Hip X-ray showed evidence of an acetabular cavity and femoral head destruction diagnostic of complicated septic arthritis. The patient subsequently underwent reconstructive surgery for the urethral stricture and urethral fistula via a transperineal approach followed by total hip arthroplasty.</p> <p>Conclusion</p> <p>Hip joint contamination with urine following a urethro-acetabular fistula can lead to severe and disabling complications such as septic arthritis. We recommend that every clinician should keep these fistulas in mind as a complication of penetrating urethral injury and every attempt should be made for their early diagnosis and prompt treatment.</p

GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10−13, r2 = 8.9%, β = −0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with—but is statistically distinct from—the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10−37, r2 = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perceptio

Sensitivity of Genome-Wide-Association Signals to Phenotyping Strategy: The PROP-TAS2R38 Taste Association as a Benchmark

Natural genetic variation can have a pronounced influence on human taste perception, which in turn may influence food preference and dietary choice. Genome-wide association studies represent a powerful tool to understand this influence. To help optimize the design of future genome-wide-association studies on human taste perception we have used the well-known TAS2R38-PROP association as a tool to determine the relative power and efficiency of different phenotyping and data-analysis strategies. The results show that the choice of both data collection and data processing schemes can have a very substantial impact on the power to detect genotypic variation that affects chemosensory perception. Based on these results we provide practical guidelines for the design of future GWAS studies on chemosensory phenotypes. Moreover, in addition to the TAS2R38 gene past studies have implicated a number of other genetic loci to affect taste sensitivity to PROP and the related bitter compound PTC. None of these other locations showed genome-wide significant associations in our study. To facilitate further, target-gene driven, studies on PROP taste perception we provide the genome-wide list of p-values for all SNPs genotyped in the current study

Chemical Addressability of Ultraviolet-Inactivated Viral Nanoparticles (VNPs)

. Thus, inactivation of the virus RNA genome is important for biosafety considerations, however the surface characteristics and chemical reactivity of the particles must be maintained in order to preserve chemical and structural functionality. were shown to maintain particle structure and chemical reactivity, and cellular binding properties were similar to CPMV-WT. applications

Crystal structure and proteomics analysis of empty virus-like particles of Cowpea mosaic virus

Empty virus-like particles (eVLPs) of Cowpea mosaic virus (CPMV) are currently being utilized as reagents in various biomedical and nanotechnology applications. Here, we report the crystal structure of CPMV eVLPs determined using X-ray crystallography at 2.3 Å resolution and compare it with previously reported cryo-electron microscopy (cryo-EM) of eVLPs and virion crystal structures. Although the X-ray and cryo-EM structures of eVLPs are mostly similar, there exist significant differences at the C-terminus of the small (S) subunit. The intact C-terminus of the S subunit plays a critical role in enabling the efficient assembly of CPMV virions and eVLPs, but undergoes proteolysis after particle formation. In addition, we report the results of mass spectrometry-based proteomics analysis of coat protein subunits from CPMV eVLPs and virions that identify the C-termini of S subunits undergo proteolytic cleavages at multiple sites instead of a single cleavage site as previously observed

Lumazine Synthase Protein Nanoparticle-Gd(III)-DOTA Conjugate as a T1 contrast agent for high-field MRI

With the applications of magnetic resonance imaging (MRI) at higher magnetic fields increasing, there is demand for MRI contrast agents with improved relaxivity at higher magnetic fields. Macromolecule-based contrast agents, such as protein-based ones, are known to yield significantly higher r(1) relaxivity at low fields, but tend to lose this merit when used as T-1 contrast agents (r(1)/r(2) = 0.5 similar to 1), with their r(1) decreasing and r(2) increasing as magnetic field strength increases. Here, we developed and characterized an in vivo applicable magnetic resonance (MR) positive contrast agent by conjugating Gd(III)-chelating agent complexes to lumazine synthase isolated from Aquifex aeolicus (AaLS). The r(1) relaxivity of Gd(III)-DOTA-AaLS-R108C was 16.49 mM(-1)s(-1) and its r(1)/r(2) ratio was 0.52 at the magnetic field strength of 7 T. The results of 3D MR angiography demonstrated the feasibility of vasculature imaging within 2 h of intravenous injection of the agent and a significant reduction in T-1 values were observed in the tumor region 7 h post-injection in the SCC-7 flank tumor model. Our findings suggest that Gd(III)-DOTA-AaLS-R108C could serve as a potential theranostic nanoplatform at high magnetic field strength.open0

Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care