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Respiratory supercomplexes:structure,function and assembly

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Protein & Cell 2013年第8期4卷 582-590页

作者： Rasika Vartak Christina Ann-marie Porras Yidong Bai Department of Cellular and Structural Biology University of Texas Health Science Center at San AntonioSan AntonioTX 78229USA

The mitochondrial respiratory chain consists of 5 enzyme complexes that are responsible for ATP generation.The paradigm of the electron transport chain as discrete enzymes diffused in the inner mitochondrial membrane has been replaced by the solid state supercomplex model wherein the respiratory complexes associate with each other to form supramolecular complexes.Defects in these supercomplexes,which have been shown to be functionally active and required for forming stable respiratory complexes,have been associated with many genetic and neurodegenerative disorders demonstrating their biomedical signifi cance.In this review,we will summarize the functional and structural signifi cance of supercomplexes and provide a comprehensive review of their assembly and the assembly factors currently known to play a role in this process.

关键词： supercomplex mitochondrial respiration

Bone tissue engineering via growth factor delivery:from scaffolds to complex matrices

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Regenerative Biomaterials 2018年第4期5卷 197-211页

作者： Tinke-marie De Witte Lidy E.Fratila-Apachitei Amir A.Zadpoor Nicholas A.Peppas Department of Biomedical Engineering The University of Texas at AustinAustinTX 78712USA Additive Manufacturing Laboratory Department of Biomechanical EngineeringDelft University of Technology(TU Delft)2628 CD DelftThe Netherlands McKetta Department of Chemical Engineering The University of Texas at AustinAustinTX 78712USA Institute for Biomaterials Drug Delivery and Regenerative MedicineThe University of Texas at AustinAustinTX 78712USA Department of Pediatrics and Department of Surgery and Perioperative CareDell Medical SchoolThe University of Texas at AustinAustinTX 78712USA Division of Molecular Pharmaceutics and Drug Delivery College of PharmacyThe University of Texas at AustinAustinTX 78712USA

In recent years,bone tissue engineering has emerged as a promising solution to the limitations of current gold standard treatment options for bone related-disorders such as bone grafts.Bone tissue engineering provides a scaffold design that mimics the extracellular matrix,providing an architecture that guides the natural bone regeneration process.During this period,a new generation of bone tissue engineering scaffolds has been designed and characterized that explores the incorporation of signaling molecules in order to enhance cell recruitment and ingress into the scaffold,as well as osteogenic differentiation and angiogenesis,each of which is crucial to successful bone regeneration.Here,we outline and critically analyze key characteristics of successful bone tissue engineering scaffolds.We also explore candidate materials used to fabricate these scaffolds.Different growth factors involved in the highly coordinated process of bone repair are discussed,and the key requirements of a growth factor delivery system are described.Finally,we concentrate on an analysis of scaffold-based growth factor delivery strategies found in the recent literature.In particular,the incorporation of two-phase systems consisting of growth factor-loaded nanoparticles embedded into scaffolds shows great promise,both by providing sustained release over a therapeutically relevant timeframe and the potential to sequentially deliver multiple growth factors.

关键词： scaffolds bone growth tissue engineering growth factor delivery

Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium

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International Journal of Oral Science 2013年第2期5卷 75-84页

作者： Audrey Rakian Wu-Chen Yang Jelica Gluhak-Heinrich Yong Cui marie A Harris Demitri Villarreal Jerry Q Feng Mary MacDougall Stephen E Harris Department of Periodontics University of Texas Health Science Center at San Antonio Baylor College of Dentistry Texas A&M System University of Alabama School of Dentistry

Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers of the periodontal ligament （PDL）. However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 （Bmp2） in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 （PO）, followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2gene is removed from Sp7＋（Osterix＋） cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC （Nfic）, periostin and α-SMA＋ cells. Third, there is a failure to produce vascular endothelial growth factor A （VEGF-A） in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOsp7-cre＇EGFe. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOsp7-cre＇EGFe. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.

关键词： Bmp2 gene cementum dentinogenesis periodontium development root formation

Immunogenetic factors driving formation of ultralong VH CDR3 in Bos taurus antibodies

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Cellular & Molecular Immunology 2019年第1期16卷 53-64页

作者： Thaddeus C Deiss Melissa Vadnais Feng Wang Patricia L Chen Ali Torkamani Waithaka Mwangi marie-Paule Lefranc Michael F Criscitiello Vaughn V Smider Comparative Immunogenetics Laboratory Department of Veterinary PathobiologyCollege of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTX 77843USA Department of Molecular Medicine The Scripps Research InstituteLa JollaCA 92037USA California Institute for Biomedical Research La JollaCA 92037USA Department of Integrative Structural and Computational Biology The Scripps Research InstituteLa JollaCA 92037USA Department of Diagnostic Medicine and Pathobiology College of Veterinary MedicineKansas State UniversityManhattanKS 66506USA IMGT the International ImMunoGeneTics information systemLaboratoire d’ImmunoGénétique MoléculaireInstitut de Génétique HumaineCNRSUniversity of MontpellierMontpellier 34396France Department of Microbial Pathogenesis and Immunology College of MedicineTexas A&M UniversityBryanTX 77807USA Fabrus Inc.La JollaCA 92037USA

The antibody repertoire of Bos taurus is characterized by a subset of variable heavy(VH)chain regions with ultralong third complementarity determining regions(CDR3)which,compared to other species,can provide a potent response to challenging antigens like HIV env.These unusual CDR3 can range to over seventy highly diverse amino acids in length and form uniqueβ-ribbon‘stalk’and disulfide bonded‘knob’structures,far from the typical antigen binding site.The genetic components and processes for forming these unusual cattle antibody VH CDR3 are not well understood.Here we analyze sequences of Bos taurus antibody VH domains and find that the subset with ultralong CDR3 exclusively uses a single variable gene,IGHV1-7(VHBUL)rearranged to the longest diversity gene,IGHD8-2.An eight nucleotide duplication at the 3′end of IGHV1-7 encodes a longer V-region producing an extended Fβ-strand that contributes to the stalk in a rearranged CDR3.A low amino acid variability was observed in CDR1 and CDR2,suggesting that antigen binding for this subset most likely only depends on the CDR3.Importantly a novel,potentially AID mediated,deletional diversification mechanism of the B.taurus VH ultralong CDR3 knob was discovered,in which interior codons of the IGHD8-2 region are removed while maintaining integral structural components of the knob and descending strand of the stalk in place.These deletions serve to further diversify cysteine positions,and thus disulfide bonded loops.Hence,both germline and somatic genetic factors and processes appear to be involved in diversification of this structurally unusual cattle VH ultralong CDR3 repertoire.

关键词： bovine complementarity determining region 3 repertoire diversification deletions immunoglobulin heavy chain

Challenge of hepatitis C in Egypt and hepatitis B in Mauritania

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World Journal of Hepatology 2018年第9期10卷 549-557页

作者： Issam I Raad Anne-marie Chaftari Harrys A Torres Ehab Mouris Ayoub Liliane Iskander Narouz Jalen Bartek Ray Hachem Department of Infectious Diseases Infection Control and Employee Healththe University of Texas M.D. Anderson Cancer Center Department of Internal Medicine Harpur Memorial Hospital Faculty of Nursing Cairo University Division of Internal Medicine the University of Texas M.D. Anderson Cancer Center

Egypt has one of the highest prevalence rates of hepatitis C virus(HCV) in the world,mostly with genotype 4 that is highly associated with severe fibrosis. As a consequence,hepatocellular carcinoma has become the leading cause of cancer in this country. Mauritania is a highly endemic area for hepatitis B virus(HBV). HBV and HCV could both be iatrogenically transmitted through infected blood products,infected needles,and medical equipment improperly sterilized. Adequate and efficient healthcare and public health measures with good surveillance programs,access for screening,prevention strategies,and successful treatment are needed to halt the spread of these diseases. Herein,we have reviewed the epidemiology,modes of transmission,predisposing factors,and novel treatment modalities of these viruses. We have proposed practices and interventions to decrease the risk of transmission of HCV and HBV in the affected countries,including strict adherence to standard precautions in the healthcare setting,rigorous education and training of patients and healthcare providers,universal screening of blood donors,use of safetyengineered devices,proper sterilization of medical equipment,hepatitis B vaccination,as well as effective direct-acting antiviral agents for the treatment of HCV.

关键词： Hepatitis B virus Hepatocellular carcinoma Hospital acquired infection World Health Organization Hepatitis delta virus Hepatitis C virus

Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes

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Bone Research 2019年第1期7卷 41-53页

作者： Delphine B.Maurel Tsutomu Matsumoto Julian A.Vallejo Mark L.Johnson Sarah L.Dallas Yukiko Kitase Marco Brotto Michael J.Wacker marie A.Harris Stephen E.Harris Lynda F.Bonewald Department of Oral and Craniofacial Sciences University of Missouri-Kansas City School of DentistryKansas CityMOUSA Department of Anatomy and Cell Biology Indiana University School of MedicineIndianapolisINUSA Bone.Muscle Collaborative Sciences College of Nursing and Health InnovationUniversity of Texas at ArlingtonArlingtonUSA Department of Biomedical Sciences University of Missouri-Kansas City School of MedicineKansas CityMOUSA University of texas Health Science Center San AntonioTXUSA Department of Orthopaedic Surgery Indiana University School of MedicineIndianapolisINUSA Pharmaceutical Sciences Department Universite de BordeauxBio-TisINSERM Unité1026 BioTis146 Rue Léo Saignat33076 BordeauxFrance

Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology,function and disease.While numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts,few target osteocytes specifically,particularly mature osteocytes.Our goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a Bac construct containing the 5’and 3’regions of the Sost gene(Sost ERT2 Cre).Four founder lines were crossed with the Ai9 Cre reporter mice.One founder line showed high and specific activity in mature osteocytes.Bones and organs were imaged and fluorescent signal quantitated.While no activity was observed in 2 day old pups,by 2 months of age some osteocytes were positive as osteocyte Cre activity became spontaneous or‘leaky’with age.The percentage of positive osteocytes increased following tamoxifen injection,especially in males,with 43%to 95%positive cells compared to 19%to 32%in females.No signal was observed in any bone surface cell,bone marrow,nor in muscle with or without tamoxifen injection.No spontaneous signal was observed in any other organ.However,with tamoxifen injection,a few positive cells were observed in kidney,eye,lung,heart and brain.All other organs,28 in total,were negative with tamoxifen injection.However,with age,a muscle phenotype was apparent in the Sost-ERT2 Cre mice.Therefore,although this mouse model may be useful for targeting gene deletion or expression to mature osteocytes,the muscle phenotype may restrict the use of this model to specific applications and should be considered when interpreting data.

关键词： cell knowledge model

Assessing the Impact of the Lead/Lag Times on the Project Duration Estimates in Highway Construction

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Journal of Architectural Environment & Structural Engineering Research 2021年第3期4卷 47-62页

作者： Mohamed Abdel-Raheem Jennifer Reyes Xiaohui Wang Grecia Silva Sanchez Alyssa marie Garza Department of Civil Engineering University of Texas Rio Grande ValleyEdinburgTX78539the U.S. School of Mathematical&Statistical Sciences University of Texas Rio Grande ValleyEdinburgTX78539the U.S.

The literature mentions multiple factors that can affect the accuracy of estimating the project duration in highway construction,such as weather,location,and soil conditions.However,there are other factors that have not been explored,yet they can have significant impact on the accuracy of the project time estimate.Recently,TxDOT raised a concern regarding the importance of the proper estimating of the lead/lag times in project schedules.These lead/lag times are often determined based on the engineer’s experience.However,inaccurate estimates of the lead/lag time can result in unrealistic project durations.In order to investigate this claim,the study utilizes four time sensitivity measures(TSM),namely the Criticality Index(CI),Significance Index(SI),Cruciality Index(CRI),and the Schedule Sensitivity Index(SSI)to statistically analyze and draw conclusions regarding the impact of the lead/lag time estimates on the total duration in highway projects.An Excel-based scheduling software was developed with Monte Carlo simulation capabilities to calculate these TSM.The results from this paper show that the variability of some lead/lag times can significantly impact the accuracy of the estimated total project duration.It was concluded that the current practices used for estimating the lead/lag times are insufficient.As such,it is recommended to utilize more robust methods,such as the time sensitivity measures,to accurately estimate the lead/lad times in the projects scheduled.

关键词： Scheduling Highway projects Lead Lag Time sensitivity measures

Comparing Methods of Applying the Propensity Score to Control Selection Bias in Studies of Prostate Cancer

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Journal of Health Science 2016年第5期4卷 262-276页

作者： Xiao Fang1 Vahakn Bedig Shahinian Kristin marie Sheffield Alai Tan Daniel Chaim Jupiter Yong-Fang Kuo Department of Preventive Medicine and Community Health the University of Texas Medical Branch Galveston 77555 USA University of Michigan Internal Medicine-Nephrology Ann Arbor USA Global Patient Outcomes and Real World Evidence Eli Lilly Indianapolis 46285 USA Sealy Center on Aging the Ohio State University Columbus 43210 USA

Phased,chromosome-scale genome assemblies of tetraploid potato reveal a complex genome,transcriptome,and predicted proteome landscape underpinning genetic diversity

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Molecular Plant 2022年第3期15卷 520-536页

作者： Genevieve Hoopes Xiaoxi Meng John P.Hamilton Sai Reddy Achakkagari Fernanda de Alves Freitas Guesdes marie E.Bolger Joseph J.Coombs Danny Esselink Natalie R.Kaiser Linda Kodde Maria Kyriakidou Brian Lavrijssen Natascha van Lieshout Rachel Shereda Heather K.Tuttle Brieanne Vaillancourt Joshua C.Wood Jan Mde Boer Nolan Bornowski Peter Bourke David Douches Herman Jvan Eck Dave Ellis Max J.Feldman Kyle M.Gardner Johannes C.P.Hopman Jiming Jiang Walter S.De Jong Joseph C.Kuhl Richard G.Novy Stan Oome Vidyasagar Sathuvalli Ek Han Tan Remco A.Ursum M.Isabel Vales Kelly Vining Richard G.F.Visser Jack Vossen G.Craig Yencho Noelle L.Anglin Christian W.B.Bachem Jeffrey B.Endelman Laura M.Shannon Martina V.Stromvik Helen H.Tai Bjorn Usadel C.Robin Buell Richard Finkers Department of Plant Biology Michigan State UniversityEast LansingMI 48824USA Department of Horticultural Science University of MinnesotaSt.PaulMN 55108USA Department of Plant Science McGill UniversitySainte-Anne-de-BellevueQC H9X 3V9Canada Plant Breeding Wageningen University&ResearchPlant Breeding6708 PB Wageningenthe Netherlands IBG-4 Bioinformatics Forschungszentrum JülichWilhelm Johnen Str52428 JülichGermany Department of Plant Soiland Microbial SciencesMichigan State UniversityEast LansingMI 48824USA Bayer Crop Science WoodlandCA 95695USA Averis Seeds B.V. 9640 AA Veendamthe Netherlands International Potato Center 1895 Avenida La MolinaLimaPeru USDA-ARS ProsserWA 99350USA Agriculture and Agri-Food Canada Fredericton Research and Development Centre FrederictonNB E3B 4Z7Canada School of Integrative Plant Science Cornell UniversityIthacaNY 14853-1901USA Department of Plant Sciences University of IdahoMoscowID 83844USA USDA-ARS Small Grains and Potato Germplasm ResearchAberdeenID 83210USA HZPC Research B.V. Edisonweg 58501 XG Jourethe Netherlands Department of Crop and Soil Science Oregon State UniversityHermistonOR 97838USA School of Biology and Ecology University of Maine5735 Hitchner Hall OronoME 04469USA Department of Horticultural Sciences Texas A&M UniversityCollege StationTX 77843-2133USA Department of Horticulture Oregon State UniversityCorvallisOR 97331USA Department of Horticultural Science North Carolina State UniversityRaleighNC 27695-7609USA Department of Horticulture University of Wisconsin-MadisonMadisonWI 53706USA Department of Horticulture Michigan State UniversityEast LansingMI 48824USA Institute for Biological Data Science Heinrich Heine UniversityDusseldorf40225 DusseldorfGermany Plant Resilience Institute Michigan State UniversityEast LansingMI 48824USA Present address:GenNovation B.V. Wageningenthe Netherlands

Cultivated potato is a clonally propagated autotetraploid species with a highly heterogeneous genome.Phased assemblies of six cultivars including two chromosome-scale phased genome assemblies revealed extensive allelic diversity,including altered coding and transcript sequences,preferential allele expression,and structural variation that collectively result in a highly complex transcriptome and predicted proteome,which are distributed across the homologous chromosomes.Wild species contribute to the extensive allelic diversity in tetraploid cultivars,demonstrating ancestral introgressions predating modern breeding efforts.As a clonally propagated autotetraploid that undergoes limited meiosis,dysfunctional and deleterious alleles are not purged in tetraploid potato.Nearly a quarter of the loci bore mutations are predicted to have a high negative impact on protein function,complicating breeder’s efforts to reduce genetic load.The StCDF1 locus controls maturity,and analysis of six tetraploid genomes revealed that 12 allelic variants of StCDF1 are correlated with maturity in a dosage-dependent manner.Knowledge of the complexity of the tetraploid potato genome with its rampant structural variation and embedded deleterious and dysfunctional alleles will be key not only to implementing precision breeding of tetraploid cultivars but also to the construction of homozygous,diploid potato germplasm containing favorable alleles to capitalize on heterosis in F1 hybrids.

关键词： potato allele diversity phased assembly polyploid pan-genome wild introgressions