Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids

Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders

Severe and enduring anorexia nervosa:Update and observations about the current clinical reality

Several objectives underlie the current article. First, to review historical diagnostic issues and clinical strategies for treating SE-AN. Second, to provide an overview of recent evidence informed strategies and clinical innovations for the treatment of SE-AN. Third, based on the authors' collective clinical and research experience, we offer eight observations that we believe capture the current clinical experience of patients with SE-AN. Some of these observations represent empirically testable hypotheses, but all are designed to generate a meaningful discussion about the treatment of this group of individuals with eating disorders. Finally, we hope to call clinicians, scientists, professional organizations, advocates, and policy makers to action to attend to critical issues related to the care of individuals with SE-AN. We believe that an international discussion could clarify areas of need for these patients and identify opportunities for clinical innovation that would enhance the lives of individuals with SE-AN and their families

Improved autologous cortical bone harvest and viability with 2Flute otologic burs

Objectives To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic burs improve the size, cellular content, and bone healing of autologous cortical bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration. Study Design Institutional review board-approved prospective cohort study. Methods Human autologous cortical bone chips were harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute [Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the treatment of chronic otitis media with cholesteatoma. Bone chip size, cell counts, cellular gene expression, and new bone formation were quantified. Results Bone chips were significantly larger when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (113 ± 14 μm2 vs. 66 ± 8 μm2; P < 0.05) and 4 mm diameter (70 ± 8 μm2 vs. 50 ± 3 μm2; P < 0.05). After 2 weeks in culture, cell numbers were significantly higher when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (48.7 ± 3 vs. 31.8 ± 3 cells/μg bone; P < 0.05) and 4 mm diameter (27.6 ± 1.2 vs. 8.8 ± 1.2 cells/μg bone; P < 0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase, osteocalcin). Cultured cells are able to form new bone in culture, and bone formation is facilitated by the presence of bone chips. Conclusion Use of 2Flute (Stryker Corporation) otologic burs for human autologous cortical bone harvest results in more viable bone fragments, with larger bone chips and more osteoblasts. Future studies are needed to determine if this leads to improved bone healing

Steep anomalous dispersion in coherently prepared Rb vapor

Steep dispersion of opposite signs in driven degenerate two-level atomic transitions have been predicted and observed on the D2 line of 87Rb in an optically thin vapor cell. The intensity dependence of the anomalous dispersion has been studied. The maximum observed value of anomalous dispersion [dn/dnu ~= -6x10^{-11}Hz^{-1}] corresponds to anegative group velocity V_g ~= -c/23000.Comment: 4 pages, 4 figure

Building Capacity for Cancer Research in the Era of COVID-19: Implementation and Results From an International Virtual Clinical Research Training Program in Zambia

DOI: 10.1200/GO.21.00372 JCO Global Oncology no. 8 (2022) Published online May 20, 2022. PMID: 35594499https://openworks.mdanderson.org/mozart/1024/thumbnail.jp

Roads, Railroads and Decentralization of Chinese Cities

Abstract: We investigate how the configurations of urban railroads and highways have influenced urban form in Chinese cities since 1990. Each radial highway displaces at least 5 percent of central city population to surrounding regions and ring roads displace an additional 20 percent. Each radial railroad displaces 26 percent of central city industrial GDP with ring roads displacing an additional 50 percent. Products with high weight-to-value ratios appear unresponsive to transport changes. However, products with medium and low weight-to-value ratios decentralize in response to radial railroads and ring roads. Historical transportation infrastructure provides identifying variation in more recent measures of infrastructure. J.E.L.: R4, O

Development of Gene Expression Markers of Acute Heat-Light Stress in Reef-Building Corals of the Genus Porites

Coral reefs are declining worldwide due to increased incidence of climate-induced coral bleaching, which will have widespread biodiversity and economic impacts. A simple method to measure the sub-bleaching level of heat-light stress experienced by corals would greatly inform reef management practices by making it possible to assess the distribution of bleaching risks among individual reef sites. Gene expression analysis based on quantitative PCR (qPCR) can be used as a diagnostic tool to determine coral condition in situ. We evaluated the expression of 13 candidate genes during heat-light stress in a common Caribbean coral Porites astreoides, and observed strong and consistent changes in gene expression in two independent experiments. Furthermore, we found that the apparent return to baseline expression levels during a recovery phase was rapid, despite visible signs of colony bleaching. We show that the response to acute heat-light stress in P. astreoides can be monitored by measuring the difference in expression of only two genes: Hsp16 and actin. We demonstrate that this assay discriminates between corals sampled from two field sites experiencing different temperatures. We also show that the assay is applicable to an Indo-Pacific congener, P. lobata, and therefore could potentially be used to diagnose acute heat-light stress on coral reefs worldwide