The neural processing of taste

Although there have been many recent advances in the field of gustatory neurobiology, our knowledge of how the nervous system is organized to process information about taste is still far from complete. Many studies on this topic have focused on understanding how gustatory neural circuits are spatially organized to represent information about taste quality (e.g., "sweet", "salty", "bitter", etc.). Arguments pertaining to this issue have largely centered on whether taste is carried by dedicated neural channels or a pattern of activity across a neural population. But there is now mounting evidence that the timing of neural events may also importantly contribute to the representation of taste. In this review, we attempt to summarize recent findings in the field that pertain to these issues. Both space and time are variables likely related to the mechanism of the gustatory neural code: information about taste appears to reside in spatial and temporal patterns of activation in gustatory neurons. What is more, the organization of the taste network in the brain would suggest that the parameters of space and time extend to the neural processing of gustatory information on a much grander scale

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

VERITAS Discovery of VHE Emission from the Radio Galaxy 3C 264: A Multi-Wavelength Study

The radio source 3C 264, hosted by the giant elliptical galaxy NGC 3862, was observed with VERITAS between February 2017 and May 2019. These deep observations resulted in the discovery of very-high-energy (VHE; E $>100$ GeV) $\gamma$-ray emission from this active galaxy. An analysis of $\sim$57 hours of quality-selected live time yields a detection at the position of the source, corresponding to a statistical significance of 7.8 standard deviations above background. The observed VHE flux is variable on monthly time scales, with an elevated flux seen in 2018 observations. The VHE emission during this elevated state is well-characterized by a power-law spectrum with a photon index $\Gamma = 2.20 \pm 0.27$ and flux F($>315$ GeV) = ($7.6\pm 1.2_{\mathrm stat} \pm 2.3_{\mathrm syst})\times 10^{-13}$ cm$^{-2}$ s$^{-1}$, or approximately 0.7% of the Crab Nebula flux above the same threshold. 3C 264 ($z = 0.0217$) is the most distant radio galaxy detected at VHE, and the elevated state is thought to be similar to that of the famously outbursting jet in M 87. Consequently, extensive contemporaneous multi-wavelength data were acquired in 2018 at the time of the VHE high state. An analysis of these data, including VLBA, VLA, HST, Chandra and Swift observations in addition to the VERITAS data, is presented, along with a discussion of the resulting spectral energy distribution.Comment: 19 pages, 11 figures, Accepted for publication in Astrophysical Journa

A theoretical approach to spot active regions in antimicrobial proteins

Background: Much effort goes into identifying new antimicrobial compounds able to evade the increasing resistance of microorganisms to antibiotics. One strategy relies on antimicrobial peptides, either derived from fragments released by proteolytic cleavage of proteins or designed from known antimicrobial protein regions. Results: To identify these antimicrobial determinants, we developed a theoretical approach that predicts antimicrobial proteins from their amino acid sequence in addition to determining their antimicrobial regions. A bactericidal propensity index has been calculated for each amino acid, using the experimental data reported from a high-throughput screening assay as reference. Scanning profiles were performed for protein sequences and potentially active stretches were identified by the best selected threshold parameters. The method was corroborated against positive and negative datasets. This successful approach means that we can spot active sequences previously reported in the literature from experimental data for most of the antimicrobial proteins examined. Conclusion: The method presented can correctly identify antimicrobial proteins with an accuracy of 85% and a sensitivity of 90%. The method can also predict their key active regions, making this a tool for the design of new antimicrobial drugs

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause

The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use

Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine

Varicocele management for infertility and pain: A systematic review

Despite being first described two thousand years ago, the varicocele remains a controversial multifaceted disease process with numerous biological consequences including infertility, hypogonadism, and chronic orchidalgia. The underlying mechanisms remain poorly understood and likely include hypoxia, oxidative stress, hyperthermia, anatomical aberrations, and genetics as primary components. Despite a high prevalence amongst asymptomatic fertile men, varicoceles paradoxically also represent the most common correctable cause for male infertility. In this systematic review we discuss the rich historical aspects of the varicocele and the contemporary data regarding its clinical manifestations. We performed a systematic literature review with the goal of comparing outcomes and complication rates of each of the major surgical approaches as they relate to infertility and pain. We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-compliant systematic literature review for manuscripts focused on varicocele and its biological consequences. We identified 112 studies suitable for qualitative analysis and included 56 of these for quantitative analysis, with an emphasis on infertility and chronic pain outcomes. Taken together, the clinical work to date suggests that the highest fertility rates and the lowest complication rates are associated with the microsurgical subinguinal surgical approach to varicocelectomy. In all, 26–40% of patients undergoing varicocelectomy will successfully achieve short-term spontaneous pregnancy, and up to 90% of all patients undergoing varicocelectomy for pain will have improvement and/or resolution of their symptoms. Taken together, the data support an ongoing role for varicocelectomy in both of these clinical arenas. Keywords: Varicocele, Infertility, Orchidalgia, Hypogonadism, Pampiniform plexu

A Review of Combined Phosphodiesterase-5-Inhibitors and α-Blockers versus Phosphodiesterase-5-Inhibitors Alone for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia

ABSTRACTGuidelines from the American Urological Association (AUA) and the European Association of Urology (EAU) present conflicting recommendations regarding combination therapy of phosphodiesterase 5 inhibitors (PDE5is) with α-blockers to treat benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). Use of PDE5is is widespread in the population of patients with LUTS/BPH. In this scoping review, we examine the evidence regarding the safety and efficacy of combined PDE5is and α-blockers compared to PDE5i medications alone. A search was conducted using PubMed, Cochrane, and Web of Science to identify manuscripts discussing the safety of PDE5i and α-blockers in combination or comparing this combination to PDE5is alone in the treatment of LUTS/BPH. Study designs, data, and conclusions were qualitatively analyzed. Combination therapy was found to be safe across all studies; importantly, no evidence documents increased risk of hypotension. Most studies reported added improvement in symptom and quality of life scores compared to PDE5i alone, with additional International Prostate Symptom Score (IPSS) change ranging from −1.30 to −8.50 and IPSS quality of life score change ranging from −0.15 to −1.50. Objective metrics such as postvoid residual volumes and maximum flow rate were inconsistently reported. Taken together, the current body of data suggests that combining PDE5i α-blocker therapy is safe and that there are opportunities for additional symptomatic improvement, though it should be utilized for select patients. Situations with particular utility could include patients with comorbid erectile dysfunction or without sufficient improvement on monotherapy