A Roadmap for the Human Oral and Craniofacial Cell Atlas

Oral and craniofacial tissues are uniquely adapted for continuous and intricate functioning, including breathing, feeding, and communication. To achieve these vital processes, this complex is supported by incredible tissue diversity, variously composed of epithelia, vessels, cartilage, bone, teeth, ligaments, and muscles, as well as mesenchymal, adipose, and peripheral nervous tissue. Recent single cell and spatial multiomics assays—specifically, genomics, epigenomics, transcriptomics, proteomics, and metabolomics—have annotated known and new cell types and cell states in human tissues and animal models, but these concepts remain limitedly explored in the human postnatal oral and craniofacial complex. Here, we highlight the collaborative and coordinated efforts of the newly established Oral and Craniofacial Bionetwork as part of the Human Cell Atlas, which aims to leverage single cell and spatial multiomics approaches to first understand the cellular and molecular makeup of human oral and craniofacial tissues in health and to then address common and rare diseases. These powerful assays have already revealed the cell types that support oral tissues, and they will unravel cell types and molecular networks utilized across development, maintenance, and aging as well as those affected in diseases of the craniofacial complex. This level of integration and cell annotation with partner laboratories across the globe will be critical for understanding how multiple variables, such as age, sex, race, and ancestry, influence these oral and craniofacial niches. Here, we 1) highlight these recent collaborative efforts to employ new single cell and spatial approaches to resolve our collective biology at a higher resolution in health and disease, 2) discuss the vision behind the Oral and Craniofacial Bionetwork, 3) outline the stakeholders who contribute to and will benefit from this network, and 4) outline directions for creating the first Human Oral and Craniofacial Cell Atlas

An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma

The incidence of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasing and implicated in more than 60% of all oropharyngeal carcinomas (OPSCCs). Although whole-genome, transcriptome, and proteome analyses have identified altered signaling pathways in HPV-induced HNSCCs, additional tools are needed to investigate the unique pathobiology of OPSCC. Herein, bioinformatics analyses of human HPV(+) HNSCCs revealed that all tumors express full-length E6 and identified molecular subtypes based on relative E6 and E7 expression levels. To recapitulate the levels, stoichiometric ratios, and anatomic location of E6/E7 expression, we generated a genetically engineered mouse model whereby balanced expression of E6/E7 is directed to the oropharyngeal epithelium. The addition of a mutant PIK3CAE545K allele leads to the rapid development of pre-malignant lesions marked by immune cell accumulation, and a subset of these lesions progress to OPSCC. This mouse provides a faithful immunocompetent model for testing treatments and investigating mechanisms of immunosuppression

Quantitative Treatment of Decoherence

We outline different approaches to define and quantify decoherence. We argue that a measure based on a properly defined norm of deviation of the density matrix is appropriate for quantifying decoherence in quantum registers. For a semiconductor double quantum dot qubit, evaluation of this measure is reviewed. For a general class of decoherence processes, including those occurring in semiconductor qubits, we argue that this measure is additive: It scales linearly with the number of qubits.Comment: Revised version, 26 pages, in LaTeX, 3 EPS figure

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .)

A Roadmap for the Human Oral and Craniofacial Cell Atlas

Oral and craniofacial tissues are uniquely adapted for continuous and intricate functioning, including breathing, feeding, and communication. To achieve these vital processes, this complex is supported by incredible tissue diversity, variously composed of epithelia, vessels, cartilage, bone, teeth, ligaments, and muscles, as well as mesenchymal, adipose, and peripheral nervous tissue. Recent single cell and spatial multiomics assays—specifically, genomics, epigenomics, transcriptomics, proteomics, and metabolomics—have annotated known and new cell types and cell states in human tissues and animal models, but these concepts remain limitedly explored in the human postnatal oral and craniofacial complex. Here, we highlight the collaborative and coordinated efforts of the newly established Oral and Craniofacial Bionetwork as part of the Human Cell Atlas, which aims to leverage single cell and spatial multiomics approaches to first understand the cellular and molecular makeup of human oral and craniofacial tissues in health and to then address common and rare diseases. These powerful assays have already revealed the cell types that support oral tissues, and they will unravel cell types and molecular networks utilized across development, maintenance, and aging as well as those affected in diseases of the craniofacial complex. This level of integration and cell annotation with partner laboratories across the globe will be critical for understanding how multiple variables, such as age, sex, race, and ancestry, influence these oral and craniofacial niches. Here, we 1) highlight these recent collaborative efforts to employ new single cell and spatial approaches to resolve our collective biology at a higher resolution in health and disease, 2) discuss the vision behind the Oral and Craniofacial Bionetwork, 3) outline the stakeholders who contribute to and will benefit from this network, and 4) outline directions for creating the first Human Oral and Craniofacial Cell Atlas

The influence of below-ground herbivory and defoliation of a legume on nitrogen transfer to neighbouring plants

1. Both foliar and root herbivory can alter the exudation of carbon from plant roots, which in turn can affect nitrogen availability in the soil. However, few studies have investigated the effects of herbivory on N fluxes from roots, which can directly increase N availability in the soil and uptake by neighbouring plants. Moreover, the combined effects of foliar and root herbivory on N fluxes remains unexplored. 2. We subjected the legume white clover (Trifolium repens L.) to defoliation (through clipping) and root herbivory (by an obligate root-feeding nematode, Heterodera trifolii Goggart) to examine how these stresses individually, and simultaneously, affected the transfer of T. repens-derived N to neighbouring perennial ryegrass (Lolium perenne L.) plants using 15N stable-isotope techniques. We also examined the effects of defoliation and root herbivory on the size of the soil microbial community and the growth response of L. perenne. 3. Neither defoliation nor root herbivory negatively affected T. repens biomass. On the contrary, defoliation increased root biomass (34%) and total shoot production by T. repens (100%). Furthermore, defoliation resulted in a fivefold increase in T. repens-derived 15N recovered in L. perenne roots, and increased the size of the soil microbial biomass (77%). In contrast, root herbivory by H. trifolii slightly reduced 15N transfer from T. repens to L. perenne when T. repens root 15N concentration was included as a covariate, and root herbivory did not affect microbial biomass. Growth of L. perenne was not affected by any of the treatments. 4. Our findings demonstrate that defoliation of a common grassland legume can substantially increase the transfer of its N to neighbouring plants by directly affecting below-ground N fluxes. These finding require further examination under field conditions but, given the prevalence of N-limitation of plant productivity in terrestrial ecosystems, increased transfer of N from legumes to non-N-fixing species could alter competitive interactions, with implications for plant community structure

sj-docx-1-jdr-10.1177_00220345231191115 – Supplemental material for Biogeographical Impacts of Dental, Oral, and Craniofacial Microbial Reservoirs

Supplemental material, sj-docx-1-jdr-10.1177_00220345231191115 for Biogeographical Impacts of Dental, Oral, and Craniofacial Microbial Reservoirs by Q.T. Easter, B. Fernandes Matuck, B.M. Warner and K.M. Byrd in Journal of Dental Research</p

Intracellular innate resistance to bacterial pathogens

Mammalian innate immunity stimulates antigen-specific immune responses and acts to control infection prior to the onset of adaptive immunity. Some bacterial pathogens replicate within the host cell and are therefore sheltered from some protective aspects of innate immunity such as complement. Here we focus on mechanisms of innate intracellular resistance encountered by bacterial pathogens and how some bacteria can evade destruction by the innate immune system. Major strategies of intracellular antibacterial defence include pathogen compartmentalization and iron limitation. Compartmentalization of pathogens within the host endocytic pathway is critical for generating high local concentrations of antimicrobial molecules, such as reactive oxygen species, and regulating concentrations of divalent cations that are essential for microbial growth. Cytosolic sensing, autophagy, sequestration of essential nutrients and membrane attack by antimicrobial peptides are also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71916/1/j.1462-5822.2006.00795.x.pd