No evidence of flavour-nutrient learning in a two-week ‘home exposure’ study in humans

Flavour-nutrient learning is robust in animals but remains elusive in humans. Recent evidence suggests flavour-nutrient learning may be more likely to occur with beverages that contain relatively few calories (compared to no calories), while others show that learned associations can influence satiation, without an effect on preference. The objective of this research was to determine whether acquired liking for a caloric drink could be observed in a ‘home learning’ context over 2 weeks, and whether it is impacted by viscosity. In combination, we also explored changes in learning relating to fullness and expected satiety. In a double-blind study, participants (N = 83; BMI = 23.3 kg/m2) were randomly allocated to one of four groups differing in either calories (0 kcal vs. 112.5 kcal) or viscosity (low vs. high) and consumed a novel-flavoured drink over 15 days. Measures of flavour (10 ml sample) and beverage liking, grip force (a measure of beverage reward value), fullness, and expected satiety were taken at the start and the end of the study. While the high-viscous beverages were less liked (M = 40.3 mm, SD = 24.7) than the low viscous beverages (M = 64.4 mm, SD = 15.3; p = .022), there was no evidence that repeated exposure to a calorie-containing beverage impacted subsequent liking for the flavour (p = .115) or for the beverage (p = .448), grip force (ps > .26), fullness, and expected satiety (ps > .12). Accordingly, we conclude that we found no evidence of flavour-nutrient learning and flavour-satiety learning. This null finding accords with previous observations indicating that humans do not acquire flavour-nutrient associations as readily as some non-human animals

The essential role of other effective area-based conservation measures in achieving big bold conservation targets

Continued biodiversity loss has prompted calls for half of the planet to be set aside for nature - including E. O Wilson's "Half-Earth" approach and the Wild Foundation's "Nature Needs Half" initiative. These efforts have provided a necessary wake-up call and drawn welcome global attention for the urgent need for increased action on conserving biodiversity and nature in general. Yet they have also sparked debate within the conservation community, particularly due to the huge practical and political obstacles to establishing or expanding protected areas on this scale. The new designation of "other effective area-based conservation measures" (OECMs) provides the opportunity for formal recognition of and support for areas delivering conservation outcomes outside the protected area estate. We argue that OECMs are essential to the achievement of big and bold conservation targets such as Half-Earth. But integration of OECMs into the conservation estate requires fundamental changes in protected area planning and how the conservation community deals with human rights and social safeguards issues; it therefore challenges our understanding of what constitutes "conservation". It will only succeed if the key drivers of biodiversity and ecosystem service loss are addressed in the whole planet. A broad, multifaceted and innovative approach, coupled with ambitious targets, provides our best hope yet of addressing complex conservation challenges. (C) 2018 Published by Elsevier B.V.Peer reviewe

Impact of vulvovaginal health on postmenopausal women: A review of surveys on symptoms of vulvovaginal atrophy

Several recent, large-scale studies have provided valuable insights into patient perspectives on postmenopausal vulvovaginal health. Symptoms of vulvovaginal atrophy, which include dryness, irritation, itching, dysuria, and dyspareunia, can adversely affect interpersonal relationships, quality of life, and sexual function. While approximately half of postmenopausal women report these symptoms, far fewer seek treatment, often because they are uninformed about hypoestrogenic postmenopausal vulvovaginal changes and the availability of safe, effective, and well-tolerated treatments, particularly local vaginal estrogen therapy. Because women hesitate to seek help for symptoms, a proactive approach to conversations about vulvovaginal discomfort would improve diagnosis and treatment

The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding

The validity of the identification and classification of human cancer using antibodies to detect biomarker proteins depends upon antibody specificity. Antibodies that bind to the tumour-suppressor protein p16INK4a are widely used for cancer diagnosis and research. In this study we examined the specificity of four commercially available anti-p16INK4a antibodies in four immunological applications. The antibodies H-156 and JC8 detected the same 16 kDa protein in western blot and immunoprecipitation tests, whereas the antibody F-12 did not detect any protein in western blot analysis or capture a protein that could be recognised by the H-156 antibody. In immunocytochemistry tests, the antibodies JC8 and H-156 detected a predominately cytoplasmic localised antigen, whose signal was depleted in p16INK4a siRNA experiments. F-12, in contrast, detected a predominately nuclear located antigen and there was no noticeable reduction in this signal after siRNA knockdown. Furthermore in immunohistochemistry tests, F-12 generated a different pattern of staining compared to the JC8 and E6H4 antibodies. These results demonstrate that three out of four commercially available p16INK4a antibodies are specific to, and indicate a mainly cytoplasmic localisation for, the p16INK4a protein. The F-12 antibody, which has been widely used in previous studies, gave different results to the other antibodies and did not demonstrate specificity to human p16INK4a. This work emphasizes the importance of the validation of commercial antibodies, aside to the previously reported use, for the full verification of immunoreaction specificity

Application of Fluorescent Protein Expressing Strains to Evaluation of Anti-Tuberculosis Therapeutic Efficacy In Vitro and In Vivo

The slow growth of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), hinders development of new diagnostics, therapeutics and vaccines. Using non-invasive real-time imaging technologies to monitor the disease process in live animals would facilitate TB research in all areas. We developed fluorescent protein (FP) expressing Mycobacterium bovis BCG strains for in vivo imaging, which can be used to track bacterial location, and to quantify bacterial load in live animals. We selected an optimal FP for in vivo imaging, by first cloning six FPs: tdTomato, mCherry, mPlum, mKate, Katushka and mKeima, into mycobacteria under either a mycobacterial Hsp60 or L5 promoter, and compared their fluorescent signals in vitro and in vivo. Fluorescence from each FP-expressing strain was measured with a multimode reader using the optimal excitation and emission wavelengths for the FP. After normalizing bacterial numbers with optical density, the strain expressing L5-tdTomato displayed the highest fluorescence. We used the tdTomato-labeled M. bovis BCG to obtain real-time images of pulmonary infections in living mice and rapidly determined the number of bacteria present. Further comparison between L5-tdTomato and Hsp60-tdTomato revealed that L5-tdTomato carried four-fold more tdTomato gene copies than Hsp60-tdTomato, which eventually led to higher protein expression of tdTomato. Evaluating anti-TB efficacy of rifampicin and isoniazid therapy in vitro and in vivo using the L5-tdTomato strain demonstrated that this strain can be used to identify anti-TB therapeutic efficacy as quickly as 24 h post-treatment. These M. bovis BCG reporter strains represent a valuable new tool for evaluation of therapeutics, vaccines and virulence

Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation

T follicular helper cells (Tfh) are critical for the longevity and quality of antibody-mediated protection against infection. Yet few signaling pathways have been identified to be unique solely to Tfh development. ROQUIN is a post-transcriptional repressor of T cells, acting through its ROQ domain to destabilize mRNA targets important for Th1, Th17, and Tfh biology. Here, we report that ROQUIN has a paradoxical function on Tfh differentiation mediated by its RING domain: mice with a T cell-specific deletion of the ROQUIN RING domain have unchanged Th1, Th2, Th17, and Tregs during a T-dependent response but show a profoundly defective antigen-specific Tfh compartment. ROQUIN RING signaling directly antagonized the catalytic α1 subunit of adenosine monophosphate-activated protein kinase (AMPK), a central stress-responsive regulator of cellular metabolism and mTOR signaling, which is known to facilitate T-dependent humoral immunity. We therefore unexpectedly uncover a ROQUIN–AMPK metabolic signaling nexus essential for selectively promoting Tfh responses

Resource Utilization and Cost-Effectiveness of Counselor- vs. Provider-Based Rapid Point-of-Care HIV Screening in the Emergency Department

Routine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.We employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.Estimated HIV screening costs in the provider and counselor arms averaged $8.10 and$31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of$64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations where ED staff resources may be insufficient to provide comprehensive, sustainable screening services

Acrylamide-Forming Potential and Agronomic Properties of Elite US Potato Germplasm from the National Fry Processing Trial

Processed potato (Solanum tuberosum L.) products, such as chips and French fries, contribute to the dietary intake of acrylamide, a suspected human carcinogen. One of the most promising approaches for reducing its consumption is to develop and commercialize new potato varieties with low acrylamide-forming potential. To facilitate this effort, a National Fry Processing Trial (NFPT) was conducted from 2011 to 2013 in five states. More than 140 advanced breeding lines were evaluated for tuber agronomic traits and biochemical properties from harvest through 8 mo of storage. Thirty-eight and 29 entries had significantly less acrylamide in French fries than standard varieties Russet Burbank and Ranger Russet, with reductions in excess of 50%, after one and 8 mo of storage, respectively. As in previous studies, the glucose content of raw tubers was predictive of acrylamide in finished French fries (R² = 0.64–0.77). Despite its role in acrylamide formation, tuber free asparagine was not significant, potentially because it showed relatively little variation in the NFPT population. Even when glucose was included in the model as a covariate, genotype was highly significant (p = 0.001) for predicting acrylamide, indicating there may be yet-unidentified genetic loci to target in breeding. The NFPT has demonstrated that there exist many elite US breeding lines with low acrylamide-forming potential. Our ongoing challenge is to combine this trait with complex quality attributes required by the fry processing industry.This is the publisher’s final pdf. The published article is copyrighted by the Crop Science Society of America and can be found at: https://dl.sciencesocieties.org/publications/c

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms