Combinatorial Pharyngeal Taste Coding for Feeding Avoidance in Adult Drosophila.

Taste drives appropriate food preference and intake. In Drosophila, taste neurons are housed in both external and internal organs, but the latter have been relatively underexplored. Here, we report that Poxn mutants with a minimal taste system of pharyngeal neurons can avoid many aversive tastants, including bitter compounds, acid, and salt, suggesting that pharyngeal taste is sufficient for rejecting intake of aversive compounds. Optogenetic activation of selected pharyngeal bitter neurons during feeding events elicits changes in feeding parameters that can suppress intake. Functional dissection experiments indicate that multiple classes of pharyngeal neurons are involved in achieving behavioral avoidance, by virtue of being inhibited or activated by aversive tastants. Tracing second-order pharyngeal circuits reveals two main relay centers for processing pharyngeal taste inputs. Together, our results suggest that the pharynx can control the ingestion of harmful compounds by integrating taste input from different classes of pharyngeal neurons

Effects of Laryngeal Restriction on Pharyngeal Peristalsis and Biomechanics: Clinical Implications

To date, rehabilitative exercises aimed at strengthening the pharyngeal muscles have not been developed due to the inability to successfully overload and fatigue these muscles during their contraction, a necessary requirement for strength training. The purpose of this study was to test the hypothesis that applying resistance against anterosuperior movement of the hyolaryngeal complex will overload the pharyngeal muscles and by repetitive swallowing will result in their fatigue manifested by a reduction in pharyngeal peristaltic amplitude. Studies were done in two groups. In group 1 studies 15 healthy subjects (age: 42 ± 14 yr, 11 females) were studied to determine whether imposing resistance to swallowing using a handmade device can affect the swallow-induced hyolaryngeal excursion and related upper esophageal sphincter (UES) opening. In group 2, an additional 15 healthy subjects (age 56 ± 25 yr, 7 females) were studied to determine whether imposing resistance to the anterosuperior excursion of the hyolaryngeal complex induces fatigue manifested as reduction in pharyngeal contractile pressure during repeated swallowing. Analysis of the video recordings showed significant decrease in maximum deglutitive superior laryngeal excursion and UES opening diameter (P \u3c 0.01) due to resistive load. Consecutive swallows against the resistive load showed significant decrease in pharyngeal contractile integral (PhCI) values (P \u3c 0.01). Correlation analysis showed a significant negative correlation between PhCI and successive swallows, suggesting “fatigue” (P \u3c 0.001). In conclusion, repeated swallows against a resistive load induced by restricting the anterosuperior excursion of the larynx safely induces fatigue in pharyngeal peristalsis and thus has the potential to strengthen the pharyngeal contractile function

Endothelium in the pharyngeal arches 3, 4 and 6 is derived from the second heart field.

Oxygenated blood from the heart is directed into the systemic circulation through the aortic arch arteries (AAAs). The AAAs arise by remodeling of three symmetrical pairs of pharyngeal arch arteries (PAAs), which connect the heart with the paired dorsal aortae at mid-gestation. Aberrant PAA formation results in defects frequently observed in patients with lethal congenital heart disease. How the PAAs form in mammals is not understood. The work presented in this manuscript shows that the second heart field (SHF) is the major source of progenitors giving rise to the endothelium of the pharyngeal arches 3 - 6, while the endothelium in the pharyngeal arches 1 and 2 is derived from a different source. During the formation of the PAAs 3 - 6, endothelial progenitors in the SHF extend cellular processes toward the pharyngeal endoderm, migrate from the SHF and assemble into a uniform vascular plexus. This plexus then undergoes remodeling, whereby plexus endothelial cells coalesce into a large PAA in each pharyngeal arch. Taken together, our studies establish a platform for investigating cellular and molecular mechanisms regulating PAA formation and alterations that lead to disease

Periderm invasion contributes to epithelial formation in the teleost pharynx

The gnathostome pharyngeal cavity functions in food transport and respiration. In amniotes the mouth and nares are the only channels allowing direct contact between internal and external epithelia. In teleost fish, gill slits arise through opening of endodermal pouches and connect the pharynx to the exterior. Using transgenic zebrafish lines, cell tracing, live imaging and different markers, we investigated if pharyngeal openings enable epithelial invasion and how this modifies the pharyngeal epithelium. We conclude that in zebrafish the pharyngeal endoderm becomes overlain by cells with a peridermal phenotype. In a wave starting from pouch 2, peridermal cells from the outer skin layer invade the successive pouches until halfway their depth. Here the peridermal cells connect to a population of cells inside the pharyngeal cavity that express periderm markers, yet do not invade from outside. The latter population expands along the midline from anterior to posterior until the esophagus-gut boundary. Together, our results show a novel role for the periderm as an internal epithelium becomes adapted to function as an external surface.Agência financiadora Ghent University Research Fund - BOF24J2015001401 Cancer Prevention Research Institute of Texas - RR140077info:eu-repo/semantics/publishedVersio

Fibronectin signals through integrin α5β1 to regulate cardiovascular development in a cell type-specific manner.

Fibronectin (Fn1) is an evolutionarily conserved extracellular matrix glycoprotein essential for embryonic development. Global deletion of Fn1 leads to mid-gestation lethality from cardiovascular defects. However, severe morphogenetic defects that occur early in embryogenesis in these embryos precluded assigning a direct role for Fn1 in cardiovascular development. We noticed that Fn1 is expressed in strikingly non-uniform patterns during mouse embryogenesis, and that its expression is particularly enriched in the pharyngeal region corresponding with the pharyngeal arches 3, 4, and 6. This region bears a special importance for the developing cardiovascular system, and we hypothesized that the localized enrichment of Fn1 in the pharyngeal region may be essential for cardiovascular morphogenesis. To test this hypothesis, we ablated Fn1 using the Isl1(Cre) knock-in strain of mice. Deletion of Fn1 using the Isl1(Cre) strain resulted in defective formation of the 4th pharyngeal arch arteries (PAAs), aberrant development of the cardiac outflow tract (OFT), and ventricular septum defects. To determine the cell types responding to Fn1 signaling during cardiovascular development, we deleted a major Fn1 receptor, integrin α5 using the Isl1(Cre) strain, and observed the same spectrum of abnormalities seen in the Fn1 conditional mutants. Additional conditional mutagenesis studies designed to ablate integrin α5 in distinct cell types within the Isl1(+) tissues and their derivatives, suggested that the expression of integrin α5 in the pharyngeal arch mesoderm, endothelium, surface ectoderm and the neural crest were not required for PAA formation. Our studies suggest that an (as yet unknown) integrin α5-dependent signal extrinsic to the pharyngeal endothelium mediates the formation of the 4th PAAs

Pharyngeal and Cervical Cancer Incidences Significantly Correlate with Personal UV Doses Among Whites in the United States

Because we found UV-exposed oral tissue cells have reduced DNA repair and apoptotic cell death compared with skin tissue cells, we asked if a correlation existed between personal UV dose and the incidences of oral and pharyngeal cancer in the United States. We analyzed the International Agency for Research on Cancer\u27s incidence data for oral and pharyngeal cancers by race (white and black) and sex using each state\u27s average annual personal UV dose. We refer to our data as ‘white’ rather than ‘Caucasian,’ which is a specific subgroup of whites, and ‘black’ rather than African-American because blacks from other countries around the world reside in the U.S. Most oropharyngeal carcinomas harboured human papilloma virus (HPV), so we included cervical cancer as a control for direct UV activation. We found significant correlations between increasing UV dose and pharyngeal cancer in white males (p=0.000808) and females (p=0.0031) but not in blacks. Shockingly, we also found cervical cancer in whites to significantly correlate with increasing UV dose (p=0.0154). Thus, because pharyngeal and cervical cancer correlate significantly with increasing personal UV dose in only the white population, both direct (DNA damage) and indirect (soluble factors) effects may increase the risk of HPV-associated cancer

Pear-shaped lesion of the fossa of Rosenmüller

Retention cyst of the pharyngeal mucosal space is an accumulation of trapped mucous in the mucosa or adenoids of the pharynx. It is a benign lesion, often seen on routine imaging of the head and spine. It is typically a simple cyst originating from the pharyngeal mucosa, without invasion of the surrounding structures. It is important not to misinterpret a retention cyst as a malignant tumor. Patients are usually asymptomatic and do not need treatment

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories : A Systematic Analysis for the Global Burden of Disease Study 2019

Funding Information: Conflict of Interest Disclosures: Dr Cunha reported grants from the São Paulo Research Foundation during the conduct of the study. Ms Compton reported grants from the Bill & Melinda Gates Foundation and St. Jude Children’s Research Hospital, which partially funded their employment at the Institute for Health Metrics and Evaluation at University of Washington during the conduct of the study. Ms Xu reported grants from the Bill & Melinda Gates Foundation and St. Jude Children’s Research Hospital during the conduct of the study. Prof Antunes reported support from the University of São Paulo School of Public Health during the conduct of the study and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Ministry of Health (Brazil’s official government agency). Dr Kerr reported grants or contracts from the National Institute of Dental and Craniofacial Research; payment for expert testimony; leadership or fiduciary roles in board, society, committee, or advocacy groups; paid or unpaid support from the American Board of Oral Medicine as a director; and other support from a Subaward budget. Ms Lu reported grants from the Bill & Melinda Gates Foundation and St. Jude Children’s Research Hospital, which partially funded her employment at the Institute for Health Metrics and Evaluation at University of Washington during the conduct of the study. Dr Kocarnik reported grants from the Bill & Melinda Gates Foundation during the conduct of the study. Ms Dean reported grants from the Institute for Health Metrics and Evaluation during the conduct of the study. Dr A. Ahmad reported support from Shaqra University. Dr Anwar reported support from the NUS-UGM Seed Grant from the Tahir Foundation. Prof Benzian reported institutional support as a fellow at the Stellenbosch Institute of Advanced Study. Dr Dai reported grants from the Bill & Melinda Gates Foundation during the conduct of the study and grants from Bloomberg Philanthropies outside the submitted work. Prof Gill reported support from the National Institute for Health and Care Research as a senior investigator. The views expressed in this article are those of the authors and not necessarily those of the National Institute for Health and Care Research or the UK Department of Health and Social Care. Prof V. Gupta reported grant support from the National Health and Medical Research Council of Australia. Prof V. K. Gupta reported funding support from the National Health and Medical Research Council. Dr Hussain reported support from Operational Programme Research, Development and Education. Dr Joseph reported support from the Department of Community Medicine at Kasturba Medical College, Mangalore of the Manipal Academy of Higher Education. Prof Kauppila reported support from the Sigrid Jusélius Foundation and the Finnish Cancer Foundation. Prof Khatib reported support from the Global Evidence Synthesis Initiative (GESI) and the School of Epidemiology and Public Health at Datta Meghe Institute of Higher Education and Research (DMIHER). Prof Landires reported support as a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaria Nacional de Ciencia y Tecnologia (SENACYT). Dr Morrison reported grants from The Plastic Surgery Foundation outside the submitted work. Prof Nuñez-Samudio reported support as a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaria Nacional de Ciencia y Tecnologia (SENACYT). Dr Piracha reported support from the International Center of Medical Sciences Research (ICMSR). Prof R. Radhakrishnan reported support from Wellcome Trust/DBT India Alliance. Prof Riad reported support from the NPO Systemic Risk Institute (LX22NPO5101), funded by the European Union’s NextGenerationEU. Dr Roberts reported personal fees from Biocon Biologics Ltd and grants from the National Cancer Institute outside the submitted work. Prof Saeed reported support from the International Center of Medical Sciences Research (ICMSR). Dr Samy reported support from Ain Shams University and the Egyptian Fulbright Mission Program. Dr Šekerija reported personal fees from Roche and Johnson & Johnson outside the submitted work. Dr Shahsavari reported support from the Institute for Advanced Studies in Basic Sciences (IASBS) Research Council. Mr Shrestha reported being a Doctor of Philosophy (PhD) student from the School of Pharmacy at Monash University Malaysia and received the Graduate Research Merit Scholarship to pursue his PhD. Prof J. Singh reported consultant fees from Scipher, Crealta/Horizon, MediSys, Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care Options, ClearView Healthcare Partners, Putnam Associates, Focus Forward, Navigant Consulting, Spherix, Mediq, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, Practice Point Communications, the National Institutes of Health, and the American College of Rheumatology; institutional research support from Zimmer Biomet Holdings; food and beverage payments from Intuitive Surgical/Philips Electronics North America; stock options in atai Life Sciences, Kintara Therapeutics, Intelligent Bio Solutions, Acumen Pharmaceuticals, TPT Global Tech, Vaxart, Aytu BioPharma, Adaptimmune Therapeutics, GeoVax, Pieris Pharmaceuticals, Enzolytics, Seres Therapeutics, Tonix Pharmaceuticals Holding Corp, and Charlotte’s Web Holdings; previous stock options in Amarin, Viking, and Moderna; serving on the speaker’s bureau of Simply Speaking; and serving as a member of Outcome Measures in Rheumatology (OMERACT), an organization that develops outcome measures in rheumatology and receives arms-length funding from 8 companies. Dr Suliankatchi Abdulkader reported support from Indian Council of Medical Research National Institute of Epidemiology. Mr Tovani-Palone reported support from the Saveetha Institute of Medical and Technical Sciences. Prof Unnikrishnan reported support from Kasturba Medical College, Mangalore of the Manipal Academy of Higher Education. Prof Yu reported support from the National Natural Science Foundation of China (No. 82173626). Dr Force reported grants from the Bill & Melinda Gates Foundation during the conduct of the study, as well as grants from St. Baldrick’s Foundation and the American Society of Clinical Oncology, subcontracting for St. Jude Children’s Research Hospital, and loan repayment from the National Institutes of Health Loan Repayment Program outside the submitted work. No other disclosures were reported. Funding Information: Funding/Support: Financial support for Global Burden of Disease research was provided by the Bill & Melinda Gates Foundation. Publisher Copyright: © 2023 American Medical Association. All rights reserved.Peer reviewedPublisher PD

Evidence for the prepattern/cooption model of vertebrate jaw evolution

The appearance of jaws was a turning point in vertebrate evolution because it allowed primitive vertebrates to capture and process large, motile prey. The vertebrate jaw consists of separate dorsal and ventral skeletal elements connected by a joint. How this structure evolved from the unjointed gill bar of a jawless ancestor is an unresolved question in vertebrate evolution. To understand the developmental bases of this evolutionary transition, we examined the expression of 12 genes involved in vertebrate pharyngeal patterning in the modern jawless fish lamprey. We find nested expression of Dlx genes, as well as combinatorial expression of Msx, Hand and Gsc genes along the dorso-ventral (DV) axis of the lamprey pharynx, indicating gnathostome-type pharyngeal patterning evolved before the appearance of the jaw. In addition, we find that Bapx and Gdf5/6/7, key regulators of joint formation in gnathostomes, are not expressed in the lamprey first arch, whereas Barx, which is absent from the intermediate first arch in gnathostomes, marks this domain in lamprey. Taken together, these data support a new scenario for jaw evolution in which incorporation of Bapx and Gdf5/6/7 into a preexisting DV patterning program drove the evolution of the jaw by altering the identity of intermediate first-arch chondrocytes. We present this “Pre-pattern/Cooption” model as an alternative to current models linking the evolution of the jaw to the de novo appearance of sophisticated pharyngeal DV patterning