Establishing Wiring Specificity in Visual System Circuits: From the Retina to the Brain.

The retina is a tremendously complex image processor, containing numerous cell types that form microcircuits encoding different aspects of the visual scene. Each microcircuit exhibits a distinct pattern of synaptic connectivity. The developmental mechanisms responsible for this patterning are just beginning to be revealed. Furthermore, signals processed by different retinal circuits are relayed to specific, often distinct, brain regions. Thus, much work has focused on understanding the mechanisms that wire retinal axonal projections to their appropriate central targets. Here, we highlight recently discovered cellular and molecular mechanisms that together shape stereotypic wiring patterns along the visual pathway, from within the retina to the brain. Although some mechanisms are common across circuits, others play unconventional and circuit-specific roles. Indeed, the highly organized connectivity of the visual system has greatly facilitated the discovery of novel mechanisms that establish precise synaptic connections within the nervous system.

'The book's a conversation starter': a realist exploration of the salutogenic potential of reading for pleasure.

Reading for Wellbeing (RfW) is a pilot initiative, aimed at improving mental health and well-being through supporting access and increasing opportunities to read for pleasure. RfW was implemented across six North-East local authorities in England and employed Community Reading Workers to support access to books and reading for targeted populations. The current study used realist methodology to understand context, potential mechanisms of action, acceptability and reported outcomes. Data generation and analysis were conducted iteratively, using focus groups, interviews and observations.The analysis of the collated data highlighted that a positive attitude towards reading and a desire for social connections were significant motivators for engagement with RfW. This paper postulates eight programme theories relating to that context, which describe key mechanisms within RfW linked to engagement with reading, well-being, connections and practice. The paper concludes that previous notions of positivity associated with reading for pleasure enable participants to experience RfW as a positive social encounter. This positive social encounter enhances participants' multiple resistance resources such as increased sense of self-efficacy and connectedness that could impact on their sense of well-being.

Seagrass ecosystem multifunctionality under the rise of a flagship marine megaherbivore.

Large grazers (megaherbivores) have a profound impact on ecosystem functioning. However, how ecosystem multifunctionality is affected by changes in megaherbivore populations remains poorly understood. Understanding the total impact on ecosystem multifunctionality requires an integrative ecosystem approach, which is especially challenging to obtain in marine systems. We assessed the effects of experimentally simulated grazing intensity scenarios on ecosystem functions and multifunctionality in a tropical Caribbean seagrass ecosystem. As a model, we selected a key marine megaherbivore, the green turtle, whose ecological role is rapidly unfolding in numerous foraging areas where populations are recovering through conservation after centuries of decline, with an increase in recorded overgrazing episodes. To quantify the effects, we employed a novel integrated index of seagrass ecosystem multifunctionality based upon multiple, well-recognized measures of seagrass ecosystem functions that reflect ecosystem services. Experiments revealed that intermediate turtle grazing resulted in the highest rates of nutrient cycling and carbon storage, while sediment stabilization, decomposition rates, epifauna richness, and fish biomass are highest in the absence of turtle grazing. In contrast, intense grazing resulted in disproportionally large effects on ecosystem functions and a collapse of multifunctionality. These results imply that (i) the return of a megaherbivore can exert strong effects on coastal ecosystem functions and multifunctionality, (ii) conservation efforts that are skewed toward megaherbivores, but ignore their key drivers like predators or habitat, will likely result in overgrazing-induced loss of multifunctionality, and (iii) the multifunctionality index shows great potential as a quantitative tool to assess ecosystem performance. Considerable and rapid alterations in megaherbivore abundance (both through extinction and conservation) cause an imbalance in ecosystem functioning and substantially alter or even compromise ecosystem services that help to negate global change effects. An integrative ecosystem approach in environmental management is urgently required to protect and enhance ecosystem multifunctionality.

The role of trauma and positive youth development in polysubstance use among rural middle school students: a latent class analysis.

BACKGROUND: Rural youth often begin developing polysubstance use and other risk behaviors during middle school. However, little polysubstance use research focuses on rural middle school youth. Our research uses Latent Class Analysis to understand existing patterns of rural middle school polysubstance use and risk and protective factors associated with polysubstance use. METHODS: We used survey data from a rural middle school pregnancy prevention program (N = 2,708). The survey included measures of demographics, lifetime substance use, trauma (adverse childhood experiences and bullying victimization) and aspects of youth development (parent communication on drugs and alcohol, parent connectedness and school connectedness). We used latent class analysis to produce participant polysubstance use profiles and multinomial regression to examine associations between polysubstance use, demographics, trauma and aspects of youth development. RESULTS: We categorized our participants into four latent classes. Our analysis classified 2.2% of participants as Regular Polysubstance users, 6.9% as Polysubstance experimenters, 19% as Vape + Alcohol experimenters and 71.9% as Non-Users. More adverse childhood experiences were associated with greater risk of polysubstance use and experimentation. Bullying was positively associated with greater risk of vape and alcohol experimentation. Higher reported parental and school connectedness were associated with lower risk of high frequency polysubstance use. Higher reported school connection was also associated with lower risk of polysubstance experimentation. CONCLUSION: Rural substance use prevention programs should begin during middle school, as polysubstance use development is common among rural middle schoolers. These programs should be trauma informed and focus on connectedness as a modifiable factor to reduce risk of polysubstance use development. TRIAL REGISTRATION: This article does not report results of a health care intervention on human participants.

Deletion of Gremlin-2 alters estrous cyclicity and disrupts female fertility in mice†.

Members of the differential screening-selected gene aberrative in neuroblastoma (DAN) protein family are developmentally conserved extracellular binding proteins that antagonize bone morphogenetic protein (BMP) signaling. This protein family includes the Gremlin proteins, GREM1 and GREM2, which have key functions during embryogenesis and adult physiology. While BMPs play essential roles in ovarian follicle development, the role of the DAN family in female reproductive physiology is less understood. We generated mice null for Grem2 to determine its role in female reproduction in addition to screening patients with primary ovarian insufficiency (POI) for variants in GREM2. Grem2-/- mice are viable, but female Grem2-/- mice have diminished fecundity and irregular estrous cycles. This is accompanied by significantly reduced production of ovarian anti-Müllerian hormone (AMH) from small growing follicles, leading to a significant decrease in serum AMH. Surprisingly, as AMH is a well-established marker of the ovarian reserve, morphometric analysis of ovarian follicles showed maintenance of primordial follicles in Grem2-/- mice like wild-type (WT) littermates. While Grem2 mRNA transcripts were not detected in the pituitary, Grem2 is expressed in hypothalami of WT female mice, suggesting the potential for dysfunction in multiple tissues composing the hypothalamic-pituitary-ovarian axis that contribute to the subfertility phenotype. Additionally, screening 106 women with POI identified one individual with a heterozygous variant in GREM2 that lies within the predicted BMP-GREM2 interface. In total, these data suggest that Grem2 is necessary for female fecundity by playing a novel role in regulating the HPO axis and contributing to female reproductive disease.

Wave effects on seedling establishment of three pioneer marsh species: survival, morphology and biomechanics.

BACKGROUND AND AIMS: It is important to have an in-depth mechanistic understanding of tidal marsh establishment and dynamics to ensure the long-term persistence of these valuable ecosystems. As wave forcing may be expected to impact seedling establishment, we studied the effect of water-imposed drag forces on seedling survival, morphology and biomechanical properties of three marsh pioneer species that are dominant along the salinity gradient in many areas around the world: Spartina anglica (salt to brackish), Scirpus maritimus (brackish) and Phragmites australis (brackish to fresh). METHODS: Using a newly developed plant-shaking mesocosm (PSM) that mimicked water-imposed wave drag forces, the effect of wave stress on seedling survival was examined, together with impacts on morphology and biomechanical properties. KEY RESULTS: After 7 weeks of exposure to wave stress, lowered seedling survival and growth for all species was revealed. Wave treatments increased the root/shoot biomass ratio to enhance anchorage and made seedlings more flexible (i.e. reduced flexural rigidity), which might be regarded as a mixed outcome between a stress avoidance and stress tolerance strategy. CONCLUSIONS: The different biomechanical responses between the three dominant marsh pioneer species, overall, make them less resistant to external stress. Therefore, our results indicate that the likelihood of marshes becoming established is reduced if wave energy increases. Despite the different biomechanical response of these three pioneer species to waves, the seedlings of all species were found to have low resistance to external stresses.

Fifteen-minute consultation: A guide to managing a child with a new finding of neutropenia.

OBJECTIVE: To describe a structured approach for managing a child with a new finding of neutropenia. METHOD: Literature review and consensus practice of clinicians in our regional centre. CONCLUSION: Neutropenia may arise in a variety of situations from a well child with a physiological neutropenia to a sick infant with life-threatening infection. In most cases a thoughtful history and directed examination will help to identify the severity in order to determine an appropriate care pathway. SCENARIO: A 6-year-old boy presented earlier in the day to the acute assessment unit with lethargy and a sore throat. At handover time his blood results are phoned through and show that he is neutropenic.

Lysosomal storage disorders: A review of the musculoskeletal features.

The lysosomal storage disorders are a collection of progressive, multisystem disorders that frequently present in childhood. Their timely diagnosis is paramount as they are becoming increasingly treatable. Musculoskeletal manifestations often occur early in the disease course, hence are useful as diagnostics clues. Non-inflammatory joint stiffness or pain, carpal tunnel syndrome, trigger fingers, unexplained pain crises and short stature should all prompt consideration of a lysosomal storage disorder. Recurrent ENT infections, hepatosplenomegaly, recurrent hernias and visual/hearing impairment - especially when clustered together - are important extra-skeletal features. As diagnostic and therapeutic options continue to evolve, children with lysosomal storage disorders and their families are facing more sophisticated options for screening and treatment. The aim of this article is to highlight the paediatric presentations of lysosomal storage disorders, with an emphasis on the musculoskeletal features.

Tobacco use as a risk factor for reoperation in patients with stress urinary incontinence: a multi-institutional electronic medical record database analysis.

INTRODUCTION AND HYPOTHESIS: Recurrence rates of stress urinary incontinence after surgery are reported to be between 8 to 15%. Both surgical technique and non-surgical risk factors have been shown to affect post-operative outcomes. Tobacco use is a possible risk factor that may increase the surgical failure rate, however, there are currently conflicting reports in the literature regarding the affect of tobacco use on surgical outcomes. Our objective is to evaluate the effect of tobacco use on the risk of repeat surgery for stress urinary incontinence (SUI). METHODS: We performed a retrospective cohort analysis using a de-identified clinical database from a large multi-institution electronic health records data web application EPM:ExploreTM (Explorys Inc, Cleveland, Ohio) to identify women with and without a history of tobacco use who underwent reoperation for stress urinary incontinence within 2 years of the first surgery. We then evaluated previously described risk factors for reoperation: diabetes mellitus (DM), pelvic organ prolapse (POP), anti-muscarinic (AM) use at initial surgery, obesity, and advanced age on rate of reoperation and the impact of tobacco use on these risk factors. RESULTS: Tobacco use was associated with an increased rate of a second surgery for SUI (OR=1.43, p <0.001), as was anti-muscarinic use (OR = 1.68, p<0.001), DM (OR = 1.21, p = 0.005), age >50 years (OR= 1.16, p = 0.040), and BMI > 30 kg/m2 (OR = 2.97 p<0.001). The odds of a second surgery for SUI in patients who used tobacco and anti-muscarinic medications or had pelvic organ prolapse were lower when compared to non-users. The odds of a second surgery for SUI were higher in patients who used tobacco and had asthma when compared to non-users who had asthma. CONCLUSIONS: Tobacco increases the overall risk of second surgery for SUI, however, in patients with specific risk factors, tobacco use is associated with a decrease risk of reoperation.

Crimpy inhibits the BMP homolog Gbb in motoneurons to enable proper growth control at the Drosophila neuromuscular junction.

The BMP pathway is essential for scaling of the presynaptic motoneuron arbor to the postsynaptic muscle cell at the Drosophila neuromuscular junction (NMJ). Genetic analyses indicate that the muscle is the BMP-sending cell and the motoneuron is the BMP-receiving cell. Nevertheless, it is unclear how this directionality is established as Glass bottom boat (Gbb), the known BMP ligand, is active in motoneurons. We demonstrate that crimpy (cmpy) limits neuronal Gbb activity to permit appropriate regulation of NMJ growth. cmpy was identified in a screen for motoneuron-expressed genes and encodes a single-pass transmembrane protein with sequence homology to vertebrate Cysteine-rich transmembrane BMP regulator 1 (Crim1). We generated a targeted deletion of the cmpy locus and find that loss-of-function mutants exhibit excessive NMJ growth. In accordance with its expression profile, tissue-specific rescue experiments indicate that cmpy functions neuronally. The overgrowth in cmpy mutants depends on the activity of the BMP type II receptor Wishful thinking, arguing that Cmpy acts in the BMP pathway upstream of receptor activation and raising the possibility that it inhibits Gbb activity in motoneurons. Indeed, the cmpy mutant phenotype is strongly suppressed by RNAi-mediated knockdown of Gbb in motoneurons. Furthermore, Cmpy physically interacts with the Gbb precursor protein, arguing that Cmpy binds Gbb prior to the secretion of mature ligand. These studies demonstrate that Cmpy restrains Gbb activity in motoneurons. We present a model whereby this inhibition permits the muscle-derived Gbb pool to predominate at the NMJ, thus establishing the retrograde directionality of the pro-growth BMP pathway.

Soy promotes juvenile granulosa cell tumor development in mice and in the human granulosa cell tumor-derived COV434 cell line.

Soy attracts attention for its health benefits, such as lowering cholesterol or preventing breast and colon cancer. Soybeans contain isoflavones, which act as phytoestrogens. Even though isoflavones have beneficial health effects, a role for isoflavones in the initiation and progression of diseases including cancer is becoming increasingly recognized. While data from rodent studies suggest that neonatal exposure to genistein (the predominant isoflavone in soy) disrupts normal reproductive function, its role in ovarian cancers, particularly granulosa cell tumors (GCT), is largely unknown. Our study aimed to define the contribution of a soy diet in GCT development using a genetically modified mouse model for juvenile GCTs (JGCT; Smad1 Smad5 conditional double knockout mice) as well as a human JGCT cell line (COV434). While dietary soy cannot initiate JGCT development in mice, we show that it has dramatic effects on GCT growth and tumor progression compared to a soy-free diet. Loss of Smad1 and Smad5 alters estrogen receptor alpha (Esr1) expression in granulosa cells, perhaps sensitizing the cells to the effects of genistein. In addition, we found that genistein modulates estrogen receptor expression in the human JGCT cell line and positively promotes cell growth in part by suppressing caspase-dependent apoptosis. Combined, our work suggests that dietary soy consumption has deleterious effects on GCT development.

Lower urinary tract symptoms in women with diabetes mellitus: a current review.

A literature review of the most current publications studying lower urinary tract symptoms (LUTS) and findings in diabetic women was conducted including articles from January 2013 to April 2014. Current reports consistently note that aging and obesity are significantly associated with worsened LUTS in diabetic women. Glucosuria has variable effects on urodynamic parameters and LUTS, but has a significant association with urinary tract infection (UTI) and incontinence at clinically relevant numbers, such as HbA1C values. The presence of severe nocturia in diabetic patients warrants careful surveillance for cardiovascular risks given the significant association with mortality. Diabetics appear to be at higher risk for colonization with the virulent, extended-spectrum, ß-lactamase-producing Escherichia coli and Klebsiella species in UTI. Novel therapies in glycemic control and for diabetic bladder dysfunction are undergoing animal model trials with encouraging results. The most promising of these includes stem cell therapy, although a need exists for human studies.

Genome sequences of 13 Bacillus anthracis Sterne bacteriophages isolated from soil in the western United States.

Bacillus anthracis, classified as a Tier 1 Select Agent by the Centers for Disease Control and Prevention (CDC), is the causative agent of anthrax in both humans and livestock. Herein, we report the full genome sequences of 13 bacteriophages that infect B. anthracis Sterne. These phages are grouped into four clusters and are similar to previously described Bacillus phages.

Personalized Antihypertensive Treatment Optimization With Smartphone-Enabled Remote Precision Dosing of Amlodipine During the COVID-19 Pandemic (PERSONAL-CovidBP Trial).

BACKGROUND: The objective of the PERSONAL-CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic) trial was to assess the efficacy and safety of smartphone-enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID-19 pandemic. METHODS AND RESULTS: This was an open-label, remote, dose titration trial using daily home self-monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring. Participants aged ≥18 years with uncontrolled hypertension (5-7 day baseline mean ≥135 mm Hg systolic BP or ≥85 mm Hg diastolic BP) received personalized amlodipine dose titration using novel (1, 2, 3, 4, 6, 7, 8, 9 mg) and standard (5 and 10 mg) doses daily over 14 weeks. The primary outcome of the trial was mean change in systolic BP from baseline to end of treatment. A total of 205 participants were enrolled and mean BP fell from 142/87 (systolic BP/diastolic BP) to 131/81 mm Hg (a reduction of 11 (95% CI, 10-12)/7 (95% CI, 6-7) mm Hg, P<0.001). The majority of participants achieved BP control on novel doses (84%); of those participants, 35% were controlled by 1 mg daily. The majority (88%) controlled on novel doses had no peripheral edema. Adherence to BP recording and reported adherence to medication was 84% and 94%, respectively. Patient retention was 96% (196/205). Treatment was well tolerated with no withdrawals from adverse events. CONCLUSIONS: Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App-assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long-term care. REGISTRATION: URL: clinicaltrials.gov. Identifier: NCT04559074.

GDF9 modulates the reproductive and tumor phenotype of female inha-null mice.

Intraovarian factors play important roles in coordinating germ cell and somatic cell growth in the ovary. Prior to the onset of gonadotropin stimulation and reproductive cyclicity, follicle development is dependent upon locally produced growth factors, such as the transforming growth factor beta family members inhibin, activin, and GDF9. In the absence of inhibin in prepubertal mice (Inha(-/-)), there are marked alterations in preantral follicle growth, but no evidence of ovarian tumors characteristic of adult Inha-null mice. To ascertain the contribution of GDF9 to the Inha-null phenotype, we analyzed folliculogenesis in postnatal Inha Gdf9 double knockout mice. Deletion of Gdf9 from Inha(-/-) rescues the initial growth defects found at early follicle stages in Inha(-/-) ovaries, but surprisingly enhances the onset of pretumor lesions. The normalization of growth dynamics between granulosa cells and oocytes of Inha Gdf9 double knockout mice is also accompanied by a reduction in levels of the activin/inhibin beta B subunit, Inhbb, which is upregulated in Inha(-/-) ovaries. However, at later ages, Inha Gdf9 double knockout ovaries are similar to Inha(-/-) ovaries, and show upregulation of the activin/inhibin subunits and downregulation of the growth factor, kit ligand, thus resulting in a local environment that is growth-promoting for granulosa cells but growth-inhibitory for oocytes. These data suggest a sequential mechanism of action initiated by GDF9 in the Inha knockout mouse that promotes defective folliculogenesis. These studies thus provide a novel role for GDF9 in causing reproductive defects and suppressing tumor initiation in the Inha(-/-) mouse model.

Concurrent vesicoperitoneal and vesicovaginal fistulae.

Although rare in the USA, vesicovaginal fistulae are usually associated with postoperative complications. Even more rarely seen, vesicoperitoneal fistulae can also present postoperatively. Both types of fistulae pose as diagnostically challenging and can be difficult to manage. We describe a case report of a patient with both vesicovaginal and vesicoperitoneal fistulae after a laparoscopic-assisted vaginal hysterectomy who presented with abdominal pain and anuria. Cystogram and outpatient cystoscopy were imperative in the diagnosis. She was conservatively managed with continuous bladder drainage via indwelling catheter resulting in an ideal recovery without requiring reoperation.

Effectiveness of Youth Risk Prevention Programs When Virtually Adapted.

PURPOSE: COVID-19 forced many youth risk prevention programs to be adapted to virtual formats. It remains unclear whether virtual programming is as effective as in-person programming. This study examined program logistics, differences in reach of at-risk youth and risk reduction in a youth substance use prevention program before and after being adapted to a virtual platform due to COVID-19. METHODS: Rural high school students in a substance use prevention program completed baseline and follow-up surveys. Data were included from two program cohorts, one in 2020 (In-person; N = 331) and the second in 2021 (virtual; N = 426). Survey data were analyzed to compare differences between cohorts in ability to reach at-risk youth and effects on risk reduction. Data on program logistics were drawn from open-ended facilitator questionnaires and site observation reports. These data were analyzed to understand benefits and challenges with virtual program implementation. RESULTS: In-person participants were older, in a higher grade, and reported higher rates of substance abuse, reported higher rates of substance use, sexual behaviors, and risky sex. Virtual program participants reported higher rates of unprotected sex and future intentions of unprotected sex. Neither program showed significant reduction in risk intermediary factors. Positive attitudes about the benefits of substance use increased during the virtual program. Thematic analysis revealed problems with implementing the virtual program, including low attendance and technology issues. DISCUSSION: In-person programs moved to virtual delivery may be less effective at reaching at-risk youth, may have smaller impact on risk prevention and may encounter logistical problems. Because previous research has found that technology-based interventions can be effective, future research should seek to evaluate how to strengthen evidence-based practices when delivery modality changes.

Semaphorin 6A in Retinal Ganglion Cells Regulates Functional Specialization of the Inner Retina.

To form functional circuits, neurons must settle in their appropriate cellular locations and then project and elaborate neurites to contact their target synaptic neuropils. Laminar organization within the vertebrate retinal inner plexiform layer (IPL) facilitates pre- and postsynaptic neurite targeting, yet, the precise mechanisms underlying establishment of functional IPL subdomains are not well understood. Here we explore mechanisms defining the compartmentalization of OFF and ON neurites generally, and OFF and ON direction-selective neurites specifically, within the developing IPL. We show that semaphorin 6A (Sema6A), a repulsive axon guidance cue, is required for delineation of OFF versus ON circuits within the IPL: in the Sema6a null IPL, the boundary between OFF and ON domains is blurred. Furthermore, Sema6A expressed by retinal ganglion cells (RGCs) directs laminar segregation of OFF and ON starburst amacrine cell (SAC) dendritic scaffolds, which themselves serve as a substrate upon which other retinal neurites elaborate. These results demonstrate for the first time that RGCs, the first neuron-type born within the retina, play an active role in functional specialization of the IPL. Retinal ganglion cell-dependent regulation of OFF and ON starburst amacrine cell dendritic scaffold segregation prevents blurring of OFF versus ON functional domains in the murine inner plexiform layer.

Minimal fertility defects in mice deficient in oocyte-expressed Smad4.

Bidirectional signaling between oocytes and granulosa cells is required for normal folliculogenesis. Oocyte-secreted members of the transforming growth factor beta (TGFB) family, growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15) are well-known mediators of granulosa cell function. Deletion in granulosa cells of Smad4, the common SMAD mediating all canonical TGFB-related protein signals, results in infertility. Reciprocal signaling by granulosa cell-expressed TGFB family ligands, such as activin, to the oocyte during follicle development has been proposed but not tested in vivo using conditional knockout mice. Therefore, we generated two oocyte-specific conditional knockout models for the common SMAD, Smad4, using cre recombinase expression from either the zona pellucida 3 (Zp3) or Gdf9 promoter. Cre expression from the Gdf9 promoter occurs at a slightly earlier time point in follicle development than from Zp3. Deletion of Smad4 using Zp3cre had no effect on fertility, while deletion of Smad4 with Gdf9icre resulted in a slight, but significant, reduction in litter size. These mouse models suggest a novel, although minor, role for Smad4 in the oocyte restricted to the primordial follicle stage.

Genetic analysis of chemosensory traits in human twins.

We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h(2) from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype-phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.