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The NORE1A/RASSF5 Tumor Suppressor Forms a Complex with GSK-3β to Regulate β-Catenin

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journal of Biosciences and Medicines 2024年第8期12卷 60-75页

作者： M. Lee Schmidt Howard Donninger Geoffrey j. clark Department Pharmacology and Toxicology University of Louisville Louisville USA US Worldmeds LouisvilleUSA Department of Medicine University of Louisville Louisville USA Experimental Therapeutics Program James Graham Brown Cancer Center University of Louisville Louisville USA

NORE1A (RASSF5) is a tumor suppressor of the RASSF family that is often down-regulated in human tumors. NORE1A has multiple roles in controlling cellular homeostasis, one of them being regulating levels of β-catenin by binding and modulating the ubiquitin ligase substrate recognition factor β-TrCP. β-catenin is a major executor of the Wnt pathway. The ubiquitin SCF-β-TrCP ligase complex acts on a phospho-degron site in β-catenin that can be phosphorylated by GSK-3β. We now show that in addition to binding β-TrCP, NORE1A also promotes the phosphorylation of the β-catenin phospho-degron by complexing with the kinase GSK-3β. Indeed, NORE1A enhances the formation of a GSK-3β/β-TrCP complex. A structural mutant of NORE1A that retains β-TrCP binding but will no longer interact with GSK-3β inhibits the β-catenin degrading action of NORE1A. The GSK-3β interaction with NORE1A plays an important role in the biology of NORE1A as a GSK-3β inhibitor blocks NORE1A induced senescence. Thus, we identify a new role for the tumor suppressor NORE1A: The regulation of GSK-3β. GSK-3β has many other substrates including multiple transcription factors and co-activators such as p53 and the Hippo component TAZ. The work implies that NORE1A may be able to influence all of them via this new kinase scaffolding interaction.

关键词： RAS NORE1A RASSF5 GSK-3β Beta Catenin HIPPO

Tooth loss patterns in older adults with special needs:a Minnesota cohort

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International journal of Oral Science 2011年第1期3卷 27-33页

作者： jennifer j.clark Department of Dental Ecology University of North CarolinaChapel HillNC 27599USA

This study was conducted to detail tooth loss patterns in older adults with special needs. A total of 491 elderly subjects with special needs were retrospectively selected and followed during 10/1999-12/2006. Medical, dental, cognitive, and functional assessments were abstracted from dental records and used to predict risk of tooth loss. Tooth loss events were recorded for subjects during follow-up. Chi-squared tests were used to study the association between tooth loss and the selected risk factors. Logistic, poisson, and negative binomial regressions were developed to study tooth loss patterns. Overall, 27% of the subjects lost at least one tooth during follow-up. Fourteen subjects had tooth loss events per 100 person-years. Tooth loss pattern did not differ significantly among different special-needs subgroups （i.e. community-dwelling vs. long-term care, physically disabled vs. functionally independent）. Special-needs subjects with three or more active dental conditions at arrival had more than twice the risk of losing teeth than those without any existing conditions. After adjusting other factors, the number of carious teeth or retained roots at arrival was a significant predictor of tooth loss for older adults with special needs （P=0.001）. These findings indicate that appropriately managing active caries and associated conditions is important to prevent tooth loss for older adults with special needs.

关键词： tooth loss elderly special needs

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Investigation of serum calcium and vitamin D levels in superior semicircular canal dehiscence syndrome: A case control study

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journal of Otology 2023年第1期18卷 49-54页

作者： Theofano Tikka Mohd Afiq Mohd Slim Trung Ton Anna Sheldon Louise j.clark Georgios Kontorinis Department of Ear Nose and Throat SurgeryQueen Elizabeth University Hospital345 Govan RdGlasgowG514TFUnited Kingdom

Objective: It remains unknown whether calcium metabolism has any effect on the clinical presentation of superior semicircular canal dehiscence(SSCD). Our aim was to analyse the adjusted calcium and vitamin D levels in SSCD patients compared to a control ***: This was a prospective case-control study performed in a tertiary referral center, university teaching hospital in the UK. It included all new patients with SSCD seen in a dedicated skull base clinic over a 5-year period(2015-2019) compared to a gender and age matched control group. The main outcome of the study was adjusted calcium and Vitamin D levels between the two ***: A total of 31 SSCD patients were recruited with a matched number of control patients. The mean Vitamin D level on the SSCD group was 44.8 nmoL/l(SD: 20.8) compared to 47.5 nmoL/l(SD: 27.4) on the control group(p = 0.702). Mean Adjusted calcium level was 2.34 mmoL/l(SD: 0.7) for SSCD compared to2.41 mmoL/l(SD: 0.11) for controls(p = 0.01), being within normal limits for both the SSCD and the control ***: Our study did not identify a link between Vitamin D levels and presence of SSCD. Normal adjusted calcium values were found in both groups. Despite that a statistically significant lower calcium level was found in the SSCD group which could indicate that suboptimal levels of calcium may affect the micro-environment of the otic capsule at the SSC region.

关键词： Superior semicircular canal Dehiscence Calcium Vitamin D Metabolism

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THE　RISE　AND　DECLINE　OF　THE　UNITED　STATES　SHIPPING　AND　SHIPBUILDING　INDUSTRIES

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上海交通大学学报 1994年第6期 1-10页

作者： (Captain james S.C.Chao,DCS,LL.D.john j.clark,Ph.D.)

ＴＨＥＲＩＳＥＡＮＤＤＥＣＬＩＮＥＯＦＴＨＥＵＮＩＴＥＤＳＴＡＴＥＳＳＨＩＰＰＩＮＧＡＮＤＳＨＩＰＢＵＩＬＤＩＮＧＩＮＤＵＳＴＲＩＥＳ￥（ＣａｐｔａｉｎＪａｍｅｓＳ．Ｃ．Ｃｈａｏ，ＤＣＳ，ＬＬ．Ｄ．ＪｏｈｎＪ．Ｃｌａ... 详细信息

ＴＨＥＲＩＳＥＡＮＤＤＥＣＬＩＮＥＯＦＴＨＥＵＮＩＴＥＤＳＴＡＴＥＳＳＨＩＰＰＩＮＧＡＮＤＳＨＩＰＢＵＩＬＤＩＮＧＩＮＤＵＳＴＲＩＥＳ￥（ＣａｐｔａｉｎＪａｍｅｓＳ．Ｃ．Ｃｈａｏ，ＤＣＳ，ＬＬ．Ｄ．ＪｏｈｎＪ．Ｃｌａｒｋ，Ｐｈ．Ｄ．）Ａｂｓｔｒａｃｔ...

关键词： shipping industry shipbuilding industry management

The Effects of Zinc Sulfate on the in Vitro Digestibility of Feeds in Cervids

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Open journal of Animal Sciences 2024年第3期14卷 157-167页

作者： Reese j. Thibodeaux Philip M. Urso Stanley F. Kelley Marcy M. Beverly Chris R. stewart Ian C. Dunn Gentech Diagnostics Dallas Texas USA Department of Animal Science South Dakota State University Brookings South Dakota USA School of Agricultural Sciences Sam Houston State University Huntsville Texas USA 3-S Texas Outdoors/3-S Whitetails Bedias Texas USA

The captive white-tailed deer industry has an estimated impact of 1.6 billion USD in the state of Texas alone. However, nutritional requirements for cervids are determined through research based on sheep and goats. The objective of this study was to determine the effects of zinc on differences in dry matter digestibility in vitro for white-tailed does (Odocoileus virginianus). Deer (n = 2) were ethically harvested, rumens were collected, and placed into a cooler containing warm water. Rumen contents were agitated, and fluid was filtered using cheese cloth while applying CO2. Fluid was placed into four separate incubator jars with filter bags containing a 1:1 alfalfa to coastal hay blend. Zinc doses of 0.073 mg/kg/d equivalents were added to two of the jars ( Zn), and the additional two jars received 0.00 mg/kg/d (CON). Following 48 h of incubation, in vitro true digestibility (IVTD) showed no significant differences between the control and the treatment groups. Average dry matter digested in vitro was 91.87% and 95.13%, respectively. There were no differences detected in ADF, NDF, IVTD, or OM between the treatment groups. While no detectable differences were observed in this study, this methodology did prove to be viable and functional for microbial digestion in vitro. This study can be replicated with multiple experimental units to confirm the observations of increased digestibility. Formal nutritional guidelines can be created to allow for more efficient feeding of cervids thereby reducing feed costs and continuing the growth of the captive deer industry.

关键词： Zinc IVDMD In Vitro Cervids

Comment on: Effect of intubation in patients with functional epiphora after endoscopic dacryocystorhinostomy

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International journal of Ophthalmology(English edition) 2024年第8期17卷 1576-1576页

作者： Mansooreh jamshidian-Tehrani Hossein Ghahvehchian Christopher j Compton jeremy D clark Nicole L West Mohsen Bahmani Kashkouli Department of Ophthalmology Eye Research CenterThe Five Senses Health InstituteRassoul Akram HospitalIran University of Medical SciencesTehran ***Iran Department of Ophthalmology and Visual Sciences University of Louisville School of MedicineLouisville 40202KentuckyUSA

Dear Editor,We read with interest the article by Han et al[1]in which they retrospectively assessed the effect of bicanalicular intubation for functional epiphora after a failed endoscopic dacryocystorhinostomy(DCR).They confirmed the post-DCR“functional obstruction”based on fluorescein dye disappearance(FDDT)and irrigation test[1].

关键词： intubation assessed endoscopic

Elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military Medical Research 2024年第4期11卷 479-499页

作者： Ernesto S.Nakayasu Marina A.Gritsenko Young-Mo Kim jennifer E.Kyle Kelly G.Stratton Carrie D.Nicora Nathalie Munoz Kathleen M.Navarro Daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L.Paurus Kent j.Bloodsworth Kelsey A.Allen Lisa M.Bramer Fernando Montes Kathleen A.clark Grant Tietje justin Teeguarden Kristin E.Burnum-johnson Biological Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Environmental and Molecular Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthWestern States DivisionDenverCO 80204USA Computational Analytics Division Pacific Northwest National LaboratoryRichlandWA 99352USA National Security Directorate Pacific Northwest National LaboratoryRichlandWA 99352USA Los Angeles County Fire Department Los AngelesCA 90063USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthRespiratory Health DivisionMorgantownWV 26505USA Environmental and Molecular Toxicology Oregon State UniversityCorvallisOR 97331USA

Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise *** profiles ***-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics ***:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of *** blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy *** urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid *** saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

关键词： Multi-omics analysis Intense exercise Human performance Biofluids Metabolism Immunity

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Storylines of family medicine Ⅴ:ways of thinking—honing the therapeutic self

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Family Medicine and Community Health 2024年第S03期12卷 43-51页

作者： William B Ventres Leslie A Stone johanna F Shapiro Cynthia Haq jéssica R B Leao Donald E Nease jr Liz Grant stewart W Mercer john C M Gillies Pablo González Blasco Maria Auxiliadora C De Benedetto Graziela Moreto Marcelo R Levites jennifer E DeVoe William R Phillips jane M Uygur Thomas R Egnew Colette S Stanley Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family Medicine University of California Irvine School of MedicineIrvineCaliforniaUSA Faculty of Medicine University of Sao PauloSao PauloBrazil Family Medicine University of Colorado Anschutz Medical Campus School of MedicineAuroraColoradoUSA Usher Institute Edinburgh Medical SchoolUniversity of EdinburghEdinburghUK SOBRAMFA-Medical Education and Humanism Sao PauloBrazil Family Medicine Oregon Health&Science University School of MedicinePortlandOregonUSA Family Medicine University of Washington School of MedicineSeattleWashingtonUSA General Practice Royal College of Surgeons in IrelandDublinIreland General Internal Medicine Geriatrics&Palliative MedicineTulane University School of MedicineNew OrleansLouisianaUSA

Storylines of Family Medicine is a 12-part series of thematically linked essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅴ:ways of thinking—honing the therapeutic self’,authors present the following sections:‘Reflective practice in action’,‘The doctor as drug—Balint groups’,‘Cultivating compassion’,‘Towards a humanistic approach to doctoring’,‘Intimacy in family medicine’,‘The many faces of suffering’,‘Transcending suffering’and‘The power of listening to stories.’May readers feel a deeper sense of their own therapeutic agency by reflecting on these essays.

关键词： illustration dimensions suffering

Genetic Enhancement of Indigenous Cowpea with Gamma-Ray Induced Trait Variation

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American journal of Plant Sciences 2024年第8期15卷 651-676页

作者： Mathurin Tiergnin Dabiré Minimassom Philippe Nikiéma Djibril Yonli Safiatou Sanna Wossoguim josué Gouba Siébou Palé Hamidou Traoré joseph T. B. Batieno Varra Prasad Zacharia stewart jan B. Middendorf Abhishek Rathore Anupama j. Hingane Unit de Formation et de Recherches en Sciences et Technologies Dpartement des Sciences de la Vie et de la Terre Universit Norbert ZONGO Koudougou Burkina Faso Institut de lEnvironnement et de Recherches Agricoles (INERA) Ouagadougou Burkina Faso Department of Agronomy Kansas State University Manhattan USA Center for Agriculture-Led Growth Bureau for Resilience and Food Security United States Agency for International Development United States Agency for International Development Washington DC USA International Maize and Wheat Improvement Center (CIMMYT) ICRISAT Campus Patancheru India joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture Department of Nuclear Sciences and Applications Plant Breeding and Genetics Laboratory International Atomic Energy Agency (IAEA) Seibersdorf Vienna Austria

Production of cowpea (Vigna unguiculata (L.) Walp.), a staple legume crop in Sub-Saharan Africa, faces challenges due to biotic and abiotic constraints. Induced mutagenesis was deployed to create genetic variation in two cowpea varieties (KVX396-4-5-2D and Moussa local). The radio-sensitivity tests led to determe the lethal dose 50 (LD50) corresponding to 230 Gy and 220 Gy for KVX396-4-5-2D and Moussa local varieties, respectively. Dried seeds (M0) of each variety were gamma-ray irradiated with LD50 − 50, LD50 and LD50 + 50. M1 seeds were advanced to generate M2, M3 and M4 mutants using the single-seed-descent method. M4 mutant lines were evaluated in rain-fed conditions using a randomized complete block design to assess phenotypic differences. Data on seven qualitative and eleven quantitative traits were collected. The results indicated that the mutation induced variability in three qualitative traits: in KVX 396-4-5-2D mutant lines, with flower and seed color frequencies at 2.61% and 0.56% respectively, and pod dehiscence at a frequency of 0.24%. While in Moussa local mutants, a pod color changed at a frequency of 17%. ANOVA results revealed significant differences between mutants of both varieties for all quantitative traits, including photosynthetic parameters. Positive correlations were observed between leaf diameter and 100-seed weight, and between branch number and 100-seed weight. Hierarchical clustering revealed three clusters among KVX 396-4-5-2D mutants and six clusters among Moussa local mutants. Early maturity and high foliage were induced traits in Cluster 3 of KVX 396-4-5-2D mutants while high hundred-seed weight was induced in Cluster 6 of Moussa local mutants.

关键词： Cowpea Mutagenesis Gamma Rays Radio-Sensitivity Phenotyping