1,548 results match your criteria: "Monell Chemical Senses Center; jmainland@monell.org.[Affiliation]"

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify the causes and symptoms of the disease.

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To learn from feedback (trial and error) is essential for all species. Insufficient sleep has been found to reduce the sensitivity to feedback as well as increase reward sensitivity. To determine whether insufficient sleep alters learning from positive and negative feedback, healthy participants (n = 32, mean age 29.

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Taste buds are maintained via continuous turnover of taste bud cells derived from local epithelial stem cells. A transcription factor Skn-1a (also known as Pou2f3) is required for the generation of sweet, umami (savory), and bitter taste cells that commonly express TRPM5 and CALHM ion channels. Here, we demonstrate that sodium-taste cells distributed only in the anterior oral epithelia and involved in evoking salty taste also require for their generation.

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Cellular context of IL-33 expression dictates impact on anti-helminth immunity.

Sci Immunol

November 2020

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Interleukin-33 (IL-33) is a pleiotropic cytokine that can promote type 2 inflammation but also drives immunoregulation through Foxp3T expansion. How IL-33 is exported from cells to serve this dual role in immunosuppression and inflammation remains unclear. Here, we demonstrate that the biological consequences of IL-33 activity are dictated by its cellular source.

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Tuft cells in the pathogenesis of chronic rhinosinusitis with nasal polyps and asthma.

Ann Allergy Asthma Immunol

February 2021

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Rhinology, Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Corporal Michael J. Crescenz Veterans Administration Medical Center, Veterans Health Administration, United States Department of Veteran Affairs, Philadelphia, Pennsylvania; Monell Chemical Senses Center, Philadelphia, Pennsylvania.

Objective: To review the latest discoveries regarding the role of tuft cells in the pathogenesis of chronic rhinosinusitis (CRS) with nasal polyposis and asthma.

Data Sources: Reviews and primary research manuscripts were identified from PubMed, Google, and bioRxiv using the search words airway epithelium, nasal polyposis, CRS or asthma and chemoreceptor cell, solitary chemosensory cell, brush cell, microvillus cell, and tuft cell.

Study Selections: Studies were selected on the basis of novelty and likely relevance to the functions of tuft cells in chronic inflammatory diseases in the upper and lower airways.

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Taste bud cells arise from local epithelial stem cells in the oral cavity and are continuously replaced by newborn cells throughout an animal's life. However, little is known about the molecular and cellular mechanisms of taste cell turnover. Recently, it has been demonstrated that SOX2, a transcription factor expressed in epithelial stem/progenitor cells of the oral cavity, regulates turnover of anterior tongue epithelium including gustatory and non-gustatory papillae.

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Solitary chemosensory cells are innervated by trigeminal nerve endings and autoregulated by cholinergic receptors.

Int Forum Allergy Rhinol

May 2021

Division of Rhinology, Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Background: Solitary chemosensory cells (SCCs) in the murine nasal epithelium are discrete specialized cells that respond to irritants and activate trigeminal nerve fibers through the release of acetylcholine (ACh), resulting in local neurogenic inflammation. In addition to releasing ACh, SCCs are the exclusive epithelial source of interleukin (IL)-25. In humans, SCCs are significantly expanded in sinonasal polyps (NPs).

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Development of an Effective Scalable Enantioselective Synthesis of the HIV-1 Entry Inhibitor BNM-III-170 as the Bis-Trifluoroacetate Salt.

Org Process Res Dev

November 2019

Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, PA 19104.

We report here the development and optimization of a process synthesis for the HIV-1 entry inhibitor BNM-III-170 bis-TFA salt (). The synthesis features a dynamic-kinetic resolution (DKR) to establish the initial stereogenicity. By taking advantage of significant sequence modifications of our first generation synthesis, inconjunction with the low solubility of late-stage intermediates, the overall efficiency of the synthesis has been significantly improved, now to proceed in an overall yield of 9.

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Matrix metalloprotease-mediated cleavage of neural glial-related cell adhesion molecules activates quiescent olfactory stem cells via EGFR.

Mol Cell Neurosci

October 2020

Institute of Cellular and Developmental Biology, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310027, China; Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA. Electronic address:

Quiescent stem cells have been found in multiple adult organs, and activation of these stem cells is critical to the restoration of damaged tissues in response to injury or stress. Existing evidence suggests that extrinsic cues from the extracellular matrix or supporting cells of various stem cell niches may interact with intrinsic components to initiate stem cell differentiation, but the molecular and cellular mechanisms regulating their activation are not fully understood. In the present study, we find that olfactory horizontal basal cells (HBCs) are stimulated by neural glial-related cell adhesion molecules (NrCAMs).

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Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls.

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The Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice.

Cell Mol Gastroenterol Hepatol

December 2021

Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan. Electronic address:

Article Synopsis
  • The study investigates how chemosensory signaling, specifically through the G-protein GNAT3 in metaplastic tuft cells, influences the initiation and progression of pancreatic ductal adenocarcinoma (PDA).
  • Researchers created genetically modified mice to observe the effects of disrupting GNAT3 on tumor-promoting cytokine secretion and the role of myeloid-derived suppressor cells (MDSCs) during PDA progression.
  • Results showed that the absence of GNAT3 increased cytokine levels and MDSC populations, leading to more aggressive cancer development and faster progression to metastatic carcinoma.
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Background: Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses.

Methods: We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients.

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Congenital blindness is associated with atypical morphology and functional connectivity within and from visual cortical regions; changes that are hypothesized to originate from a lifelong absence of visual input and could be regarded as a general (re) organization principle of sensory cortices. Challenging this is the fact that individuals with congenital anosmia (lifelong olfactory sensory loss) display little to no morphological changes in the primary olfactory cortex. To determine whether olfactory input from birth is essential to establish and maintain normal functional connectivity in olfactory processing regions, akin to the visual system, we assessed differences in functional connectivity within the olfactory cortex between individuals with congenital anosmia (n = 33) and matched controls (n = 33).

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Dynamics of odor sampling strategies in mice.

PLoS One

October 2020

Department of Neuroscience, Princeton University, Princeton, NJ, United States of America.

Mammalian olfactory receptor neurons in the nasal cavity are stimulated by odorants carried by the inhaled air and their activation is therefore tied to and driven by the breathing or sniffing frequency. Sniffing frequency can be deliberately modulated to alter how odorants stimulate olfactory receptor neurons, giving the animal control over the frequency of odorant exposure to potentially aid odorant detection and discrimination. We monitored sniffing behaviors and odorant discrimination ability of freely-moving mice while they sampled either decreasing concentrations of target odorants or sampled a fixed target odorant concentration in the presence of a background of increasing odorant concentrations, using a Go-NoGo behavioral paradigm.

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Background & Aims: Development of pancreatic ductal adenocarcinoma (PDA) involves acinar to ductal metaplasia and genesis of tuft cells. It has been a challenge to study these rare cells because of the lack of animal models. We investigated the role of tuft cells in pancreatic tumorigenesis.

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Background: Early rapid weight gain (RWG) increases, whereas longer durations of breastfeeding decreases, odds for later obesity.

Objectives: To determine the independent and interactive effects of early weight gain and diet on infant weight status trajectories and odds for overweight at 1 year.

Methods: We conducted secondary analysis on data from two longitudinal trials with repeated anthropometric measures.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify causes and symptoms of the disease.

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To address gaps in knowledge, our objectives were to (1) to determine whether there are age-related changes in sweet taste detection thresholds, as has been observed for sweet taste preferences, and (2) determine whether detection thresholds and taste preferences were significantly related to each other from childhood to adulthood. We combined data from studies that used the same validated psychophysical techniques to measure sucrose taste detection threshold and the most preferred sucrose concentration in children ( = 108), adolescents ( = 172), and adults ( = 205). There were significant effects of age group on both sucrose detection thresholds ( < 0.

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Dysfunction in neurophysiological systems that regulate food intake and metabolism are at least partly responsible for obesity and related comorbidities. An important component of this process is the hypothalamic melanocortin system, where an imbalance can result in severe obesity and deficits in glucose metabolism. Exercise offers many health benefits related to cardiovascular improvements, hunger control, and blood glucose homeostasis.

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Sodium-glucose cotransporter 1 as a sugar taste sensor in mouse tongue.

Acta Physiol (Oxf)

December 2020

Division of Sensory Physiology and Medical Application Sensing, Research and Development Centre for Five-Sense Devices, Kyushu University, Fukuoka, Japan.

Aim: We investigated potential neuron types that code sugar information and how sodium-glucose cotransporters (SGLTs) and T1Rs are involved.

Methods: Whole-nerve recordings in the chorda tympani (CT) and the glossopharyngeal (GL) nerves and single-fibre recordings in the CT were performed in T1R3-KO and wild-type (WT) mice. Behavioural response measurements were conducted in T1R3-KO mice using phlorizin (Phl), a competitive inhibitor of SGLTs.

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Structural Refinement of the Tubulin Ligand (+)-Discodermolide to Attenuate Chemotherapy-Mediated Senescence.

Mol Pharmacol

August 2020

Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.)

The natural product (+)-discodermolide (DDM) is a microtubule stabilizing agent and potent inducer of senescence. We refined the structure of DDM and evaluated the activity of novel congeners in triple negative breast and ovarian cancers, malignancies that typically succumb to taxane resistance. Previous structure-activity analyses identified the lactone and diene as moieties conferring anticancer activity, thus identifying priorities for the structural refinement studies described herein.

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Animals detect sick conspecifics by way of body odor that enables the receiver to avoid potential infectious transmission. Human observational studies also indicate that different types of disease are associated with more or less aversive smells. In addition, body odors from otherwise healthy human individuals smell more aversive as a function of experimentally induced systemic inflammation.

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More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

Chem Senses

October 2020

Department of Food Science, The Pennsylvania State University, Erickson Food Science Building, University Park, PA, USA.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19.

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The chemical senses of taste and smell play a vital role in conveying information about ourselves and our environment. Tastes and smells can warn against danger and also contribute to the daily enjoyment of food, friends and family, and our surroundings. Over 12% of the US population is estimated to experience taste and smell (chemosensory) dysfunction.

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Objectives: To determine whether early diet and weight gain velocity have independent or interactive effects on deciduous teeth emergence and overweight status during the first year.

Study Design: Monthly measures of anthropometry and teeth eruption were collected during a 1-year trial (0.5-12.

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