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Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis

International Journal of Oral Science 2015年第1期7卷 27-41页

作者： laura e zweifler Mudita K Patel Francisco H Nociti Jr Helen F Wimer Jose L Milln Martha J Somerman Brian L Foster National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) National Institutes of Health (NIH) Department of Prosthodontics and Periodontics Division of Periodontics School of Dentistry Campinas State University Department of Vertebrate Zoology National Museum of Natural History Smithsonian Institution Sanford Children’s Health Research Center Sanford-Burnham Medical Research Institute

Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate （Pi） to mineral inhibitor pyrophosphate （PPi）, where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase （TNAP） and ectonucleotide pyrophosphatase/phosphodiesterase 1 （NPP1）. The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the enppl null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas enppl gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.

关键词： cementum bone ectonucleotide pyrophosphatase phosphodiesterase 1 periodontal ligament progressive ankylosis protein tissue-nonspecific aJkalJne phosphatase

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Identific tion of quantitative trait loci and associated candidate genes for pregnancy success in Angus–Brahman crossbred heifers

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Journal of Animal Science and Biotechnology 2024年第1期15卷 162-170页

作者： Quinn A.Hoorn Gabriel A.Zayas eduardo e.Rodriguez laura M.Jensen Raluca G.Mateescu Peter J.Hansen Department of Animal Sciences Donald Henry Barron Reproductive and Perinatal Biology Research Programand the Genetics InstituteUniversity of FloridaGainesvilleFLUSA School of Applied Systems Biology La Trobe UniversityBundooraVIC 3083Australia

Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef *** Genome-wide association studies(GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination(AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI(PAI;n = 1,481) and pregnancy status at the end of the breeding season(PeBS;n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PeBS, respectively. In the PAI model, one quantitative trait locus(QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PeBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were *** In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations

关键词： Beef cattle Fertility GWAS QTL

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Good and bad dispositions between archaea and bacteria in the human gut:New insights from metagenomic survey and co-occurrence analysis

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Synthetic and Systems Biotechnology 2024年第1期9卷 88-98页

作者： Francesco Candeliere laura Sola Stefano Raimondi Maddalena Rossi Alberto Amaretti Department of Life Sciences University of Modena and Reggio Emilia41125 ModenaItaly Biogest-Siteia University of Modena and Reggio Emilia41125 ModenaItaly

Archaea are an understudied component of the human *** this study,the gut archaeome and bacteriome of 60 healthy adults from different region were analyzed by whole-genome shotgun *** were ubiquitously found in a wide range of abundances,reaching up to 7.2%.The dominant archaeal phylum was Methanobacteriota,specifically the family Methanobacteriaceae,encompassing more than 50%of Archaea in 50 *** previously underestimated Thermoplasmatota,mostly composed of Methanomassiliicoccaceae,dominated in 10 subjects(>50%)and was present in all others except ***,the sole other archaeal phylum,occurred in negligible concentration,except for two samples(4.6-4.8%).This finding confirmed that the human gut archaeome is primarily composed of methanogenic organisms and among the known methanogenic pathway:i)hydrogenotrophic reduction of CO_(2) is the predominant,being the genus Methanobrevibacter and the species Methanobrevibacter smithii the most abundant in the majority of the samples;ii)the second pathway,that involved Methanomassiliicoccales,was the hydrogenotrophic reduction of methyl-compounds;iii)dismutation of acetate or methyl-compounds seemed to be ***-occurrence analysis allowed to unravel correlations between Archaea and Bacteria that shapes the overall structure of the microbial community,allowing to depict a clearer picture of the human gut archaeome.

关键词： Gut microbiota Archaea Metagenome Co-occurrence Methanomassiliicoccus Methanobrevibacter smithii

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^(15)N tracers and microbial analyses reveal in situ N_(2)O sources in contrasting water regimes of a drained peatland forest

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Pedosphere 2024年第4期34卷 749-758页

作者： Mohit MASTA Mikk eSPeNBeRG laura KUUSeMeTS Jaan PÄRN Sandeep THAYAMKOTTU Holar SePP Kalle KIRSIMÄe Fotis SGOURIDIS Kuno KASAK Kaido SOOSAAR Ülo MANDeR Institute of ecology and earth Sciences University of TartuVanemuise Street 46Tartu 51003Estonia School of Geographical Sciences University of BristolUniversity RoadBristol BS81SSUK

Managed peatlands are a significant source of nitrous oxide(N_(2)O),a powerful greenhouse gas and stratospheric ozone *** to the complexity and diversity of microbial N_(2)O processes,different methods such as tracer,isotopomer,and microbiological technologies are required to understand these *** combined application of different methods helps to precisely estimate these processes,which is crucial for the future management of drained peatlands,and to mitigate soil degradation and negative atmospheric *** this study,we investigated N_(2)O sources by combining tracer,isotopomer,and microbial analysis in a drained peatland forest under flooded and drained *** average,the nitrification genes showed higher abundances in the drained treatment,and the denitrification genes showed higher abundances in the flooded *** is consistent with the underlying chemistry,as nitrification requires oxygen while denitrification is *** observed significant differences in labelled N_(2)O fluxes between the drained and flooded *** emissions of N_(2)O from the flooded treatment were nearly negligible,whereas the N_(2)O evolved from the nitrogen-15(^(15)N)-labelled ammonium(^(15)NH4+)in the drained treatment peaked at 147μg ^(15)N m^(-2) h^(-1).This initially suggested nitrification as the driving mechanism behind N_(2)O fluxes in drained peatlands,but based on the genetic data,isotopic analysis,and N_(2)O mass enrichment,we conclude that hybrid N_(2)O formation involving ammonia oxidation was the main source of N_(2)O emissions in the drained *** on the ^(15)N-labelled nitrate(^(15)NO3-)tracer addition and gene copy numbers,the low N_(2)O emissions in the flooded treatment came possibly from complete denitrification producing inert *** atomic level,we observed selective enrichment of mass 45 of N_(2)O molecule under ^(15)NH4+amendment in the drained treatment and enrichment of both masses 45 and 46 under

关键词： denitrification nitrification N_(2)O quantitative polymerase chain reaction

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Advancing immunosuppression in liver transplantation: A narrative review

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 441-448页

作者： Samuele Iesari Francesca laura Nava Ilaria elena Zais Laurent Coubeau Mariano Ferraresso evaldo Favi Jan Lerut General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico15 Via della Commenda20122 MilanItaly Institut de Recherche expérimentale et Clinique Universitécatholique de Louvain10 Avenue Hippocrate1200 BrusselsBelgium Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-Luc55 Avenue Hippocrate1200 BrusselsBelgium Department of Clinical Sciences and Community Health Universitàdegli Studi di Milano19 Via della Commenda20122 MilanItaly

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

关键词： Liver transplantation Immunosuppression Drug development Long-term results Clinical operational tolerance

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Photosynthetic response to a winter heatwave in leading and trailing edge populations of the intertidal red alga Corallina offi-cinalis(Rhodophyta)

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Acta Oceanologica Sinica 2024年第7期43卷 70-77页

作者： Regina Kolzenburg Federica Ragazzola laura Tamburello Katy R.Nicastro Christopher D.McQuaid Gerardo I.Zardi UmeåMarine Sciences Centre UmeåUniversity90571 NorrbynSweden University of Portsmouth Institute of Marine SciencePortsmouth PO49LYUK Stazione Zoologica Anton Dohrn Genova Marine CenterGenova 16126Italy Stazione Zoologica Anton Dohrn Sicily Marine CenterPalermo 90149Italy Department of Zoology and entomology Rhodes UniversityMakhanda(Grahamstown)6139South Africa Centre of Marine Sciences University of AlgarveFaro 8005-139Portugal Laboratoire d’Océanologie et de Géosciences Universitéde LilleLille 59000France Universitéde Caen Normandie Laboratoire de Biologie des Organismes et des Ecosystèmes AquatiquesCaen 14032France

Marine heatwaves(MHWs)caused by anthropogenic climate change are becoming a key driver of change at the ecosystem *** conditions experienced by marine organisms across their distribution,particularly towards the equator,are likely to approach their physiological limits,resulting in extensive mortality and subsequent changes at the population *** at the margins of their species’distribution are thought to be more sensitive to climate-induced environmental pressures than central populations,but our understanding of variability in fitness-related physiological traits in trailing versus leading-edge populations is *** a laboratory simulation study,we tested whether two leading(Iceland)and two trailing(Spain)peripheral populations of the intertidal macroalga Corallina officinalis display different levels of maximum potential quantum efficiency(Fv/Fm)resilience to current and future winter MHWs *** study revealed that ongoing and future local winter MHWs will not negatively affect leading-edge populations of ***,which exhibited stable photosynthetic efficiency throughout the *** edge populations showed a positive though non-significant trend in photosynthetic efficiency throughout winter MHWs *** and equatorward populations did not produce significantly different results,with winter MHWs having no negative affect on Fv/Fm of either ***,we found no long-term regional or population-level influence of a winter MHWs on this species’photosynthetic ***,we found no statistically significant difference in thermal stress responses between leading and trailing ***,*** showed a trend towards higher stress responses in southern than northern *** responses rest on a variety of local population traits,they are difficult to predict based solely on thermal pressures.

关键词： marginal population coralline algae climate change ecophysiology photophysiology macroalgae Fv/Fm

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Interindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk

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Research 2024年第3期6卷 417-432页

作者： laura García-Mendívil María Pérez-Zabalza Antoni Oliver-Gelabert JoséMaría Vallejo-Gil Javier Fañanás-Mastral Manuel Vázquez-Sancho Javier AndréBellido-Morales Alexánder Sebastián Vaca-Núñez Carlos Ballester-Cuenca emiliano Diez laura Ordovás esther Pueyo Biomedical Signal Interpretation and Computational Simulation group(BSICoS) Aragón Institute of Engineering ResearchUniversity of ZaragozaZaragoza 50018Spain BSICoS Instituto de Investigación Sanitaria Aragón(IISA)Zaragoza 50018Spain Centro Universitario de la Defensa(CUD) Zaragoza 50090Spain. Department of Cardiovascular Surgery University Hospital Miguel ServetZaragoza 50009Spain. Institute of experimental Medicine and Biology of Cuyo(IMBeCU) CONICETMendoza 5500Argentina. Fundación Agencia Aragonesa para la Investigación y el Desarrollo(ARAID) Zaragoza 50018Spain. Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)Zaragoza 50018Spain.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.

关键词： CX43 rhythm Independent

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Lack of evidence for germline WWP1 pathogenic variants in gastrointestinal polyposis and other phenotypes suggestive of PTeN-hamartoma-tumor syndrome

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Genes & Diseases 2024年第2期11卷 524-527页

作者： Noemi Gonzalez-Abuin Tirso Pons Teresa Fuster Isabel Quintana Mariona Terradas Gemma Aiza Joan Brunet Gabriel Capellá Heather Hampel laura Valle Hereditary Cancer Program Catalan Institute of OncologyOncobell ProgramIDIBELLHospitalet de LlobregatBarcelona 08908Spain Department of Immunology and Oncology National Center for BiotechnologySpanish National Research Council (CNB-CSIC)Madrid 28049Spain Centro de Investigación Biomédica en Red de Cáncer (CIBeRONC) Madrid 28029Spain Catalan Institute of Oncology IDIBGiGirona 17007Spain Division of Clinical Cancer Genomics Department of Medical Oncology & Therapeutic ResearchCity of Hope National Cancer CenterDuarteCA 91010USA

Germline activating variants in WWP1,which encodes an e3 ubiquitin ligase that antagonizes PTeN tumor suppressive function,have been proposed as an alternative mechanism of PTeN inactivation in PTeN-hamartoma-tumor syndrome(PHTS)-like patients with wildtype PTeN.1 More specifically,heterozygous,potentially activating wwP1 variants were first identified by Lee et al in patients affected with gastrointestinal oligopolyposis,including adenomatous,hyperplastic/serrated,and hamartomatous polyps,and occasionally with colorectal cancer(Table 1).Subsequently,based on the PHTS phenotypic features,wWP1 mutational screening was performed in patients with thyroid nodules,2 or normocephalic autism spectrum disorder(ASD),3 where germline WWP1 variants were also identified(Table S1).

关键词： WWP1 gastrointestinal polyposis

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Seismic attribute and well-log analysis for channel characterization in the upper San Andres and Grayburg formations of the Midland Basin,Texas

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energy Geoscience 2024年第2期5卷 263-278页

作者： Sumit Verma esra Yalçın Yılmaz laura Ortiz Sanguino Justin Yandell Miles A.Henderson Robert C.Trentham Department of Geosciences The University of Texas Permian BasinOdessaTXUSA School of Geosciences The University of OklahomaNormanOKUSA

The Permian Basin is one of the most prolific,and currently one of the most active,oil and gas basins in the *** Lower Permian strata in the Permian Basin have produced more than 14 billion barrels of oil(BBO),making it the largest volume of hydrocarbon in the *** in the Midland Basin during late Leonardian through early Guadalupian(ca.272-269 Ma)resulted in progradation of shelf edge and ultimately closure of the basin by Middle Permian *** analyzed a merged seismic survey covering parts of the Permian Basin(i.e.,Central Basin Platform and Midland Basin)in Andrews,ector,and Midland Counties,*** seismic survey and well logs show the presence of gently dipping(ca.1°)clinoforms in the Upper San Andres and Grayburg Formations on the eastern edge of the Central Basin Platform and western Midland *** seismic attributes,curvature,and spectral decomposition identify low sinuosity slope channels oriented north-south,but such channels do not appear beyond the *** shelf edge shifts from north to south during deposition of the Upper San Andres and Grayburg *** identify five basinward shifts noted by the migration of the shelf edge toward the basin center and the presence of channel features along the depositional *** petrophysical analysis indicates that channels cut into carbonate rocks and are filled by siliciclastic sediments;this interpretation is supported by the most negative curvature anomalies along the channel axes caused by the differential compaction between the carbonate and siliciclastic *** are a few channels with a northwest-southeast strike,which matches the direction of the Concho Lineament observed by satellite *** observations are consistent with previous interpretations of the northern Midland Basin closure during Middle-Late Permian time.

关键词： Permian shelf carbonate

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Association between baseline levels of muscular strength and risk of stroke in later life:The Cooper Center Longitudinal Study

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Journal of Sport and Health Science 2024年第5期13卷 642-649页

作者： Stephen W.Farrell David Leonard Qing Li Carolyn e.Barlow Kerem Shuval Jarett D.Berry Andjelka Pavlovic laura F.DeFina Research Division The Cooper InstituteDallasTX 75230USA Department of Internal Medicine University of Texas at Tyler School of MedicineTylerTX 75799USA

Background:Muscular strength is an important component of physical *** evaluated the relationship between baseline muscular strength and risk of stroke among adults who were aged≥65 years during ***:We included 7627 healthy adults(mean age=43.9 years,86.0%male)underwent a baseline physical examination between 1980 and *** strength was determined by 1-repetition maximum measures for bench press and leg press and categorized into age-and sex-specific tertiles for each *** fitness(CRF)was assessed via a maximal treadmill exercise *** enrolled in fee-for-service Medicare from 1999 to 2019 were included in the *** between baseline strength and stroke outcomes were estimated using a modified Cox proportional hazards *** a secondary analysis,we examined stroke risk by categories of CRF where Quintile 1=low,Quintiles 2-3=moderate,and Quintiles 4-5=high CRF based on age and ***:After 70,072 person-years of Medicare follow-up,there were 1211 earliest indications of incident *** multivariable analyses,the hazard ratio(95%confidence interval(95%CI))for stroke across bench press categories were 1.0(referent),0.96(0.83-1.11),and 0.89(0.77-1.04),respectively(p trend=0.14).The trend across categories of leg press was also non-significant(p trend=0.79).Adjusted hazard ratio(95%CI)for stroke across ordered CRF categories were 1.0(referent),0.90(0.71-1.13),and 0.72(0.57-0.92)(p trende meeting public health guidelines for muscular strengthening activities is likely to improve muscular strength as well as many health outcomes in older adults,performing such activities may not be helpful in preventing ***,meeting guidelines for aerobic activity is likely to improve CRF and lower stroke risk.

关键词： Cardiorespiratory fitness Medicare Muscular strength Stroke

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