Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

CD4+ T Cell Profile and Activation Response in Sickle Cell Disease Patients with Osteonecrosis

Recent evidence suggests that abnormalities involving CD4+T lymphocytes are associated with the pathophysiology of osteonecrosis (ON); however, few studies have addressed the CD4+T cells in ON related to sickle cell disease (SCD/ON). In addition, T cells producing multiple cytokines simultaneously are often present in the inflammatory milieu and may be implicated in the immune response observed in SCD/ON. In the present study, we aimed to characterize the functional status of CD4+T cells in SCD by simultaneously determining the frequency of IFN-γ+, IL-4+, and IL-17+ CD4+T in cell cultures under exogenous stimuli. Peripheral blood mononuclear cells (PB-MNCs) from 9 steady-state SCD patients, 15 SCD/ON patients, and 19 healthy controls had functional status of CD4+T cells analyzed. Bone marrow mononuclear cells (BM-MNCs) from 24 SCD/ON patients (SCD BM) and 18 patients with ON not related to SCD (non-SCD BM) were also analyzed. We found that PB-MNC of SCD patients with or without ON presented significantly reduced TCD4+, TCD8+, and TCD4+ naïve cell frequencies and increased frequency of circulating CD4+T cells able to simultaneously produce IFN-γ+/IL4+ and IL-17+/IL4+ compared to healthy controls. Conversely, the polyclonal stimulation of BM-MNC induced an increased frequency of CD4+IFN-γ+ and CD4+IL-17+ in SCD BM compared to non-SCD BM. The increased proportion of CD4+ T cells able to produce a broad spectrum of proinflammatory cytokines after a strong stimulus indicates that the immune system in SCD/ON patients presents an expressive pool of partially differentiated cells ready to take on effector function. It is possible that this increased subpopulation may extend to inflammatory sites of target organs and may contribute to the maintenance of inflammation and the pathophysiology of osteonecrosis in sickle cell disease

Quantification and Comprehensive Analysis of Mesenchymal Stromal Cells in Bone Marrow Samples from Sickle Cell Disease Patients with Osteonecrosis

The potential use of bone marrow mesenchymal stromal cells (BM-MSCs) for the treatment of osteonecrosis in sickle cell disease (SCD) patients is increasing. However, convenient BM-MSC quantification and functional property assays are critical factors for cell-based therapies yet to be optimized. This study was designed to quantify the MSC population in bone marrow (BM) samples from SCD patients with osteonecrosis (SCD group) and patients with osteoarticular complications not related to SCD (NS group), using flow cytometry for CD271+CD45-/low cell phenotype and CFU-F assay. We also compared expanded BM-MSC osteogenic differentiation, migration, and cytokine secretion potential between these groups. The mean total cell number, CFU-F count, and CD271+CD45-/low cells in BM mononuclear concentrate were significantly higher in SCD than in NS patients. A significant correlation between CD271+CD45-/low cell number and CFU-F counts was found in SCD (r=0.7483; p=0.0070) and NS (r=0.7167; p=0.0370) BM concentrates. An age-related quantitative reduction of CFU-F counts and CD271+CD45-/low cell number was noted. Furthermore, no significant differences in the morphology, replicative capacity, expression of surface markers, multidifferentiation potential, and secretion of cytokines were found in expanded BM-MSCs from SCD and NS groups after in vitro culturing. Collectively, this work provides important data for the suitable measurement and expansion of BM-MSC in support to advanced cell-based therapies for SCD patients with osteonecrosis

Unequal burden of Zika-associated microcephaly among populations with public and private healthcare in Salvador, Brazil

This study was supported by Oswaldo Cruz Foundation; Secretariat of Health Surveillance; Brazilian Ministry of Health; Wellcome Trust, Grant/Award Number: 102330/Z/13/Z; NSF-NIH, Grant/Award Number: 5 R01 AI052473, 5 U01 AI088752, 1 R25 TW009338, 1 R01 AI121207, F31 AI114245, R01 AI052473, U01 AI088752, R01 TW009504, and R25 TW009338. Fogarty International Center (R25 TW009338). Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) projects 2016/08727-5 and National Council for Scientific and Technological Development – CNPq. Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) projeto (PET0021/2016)Yale School of Public Health. New Haven, USAHospital Aliança. Salvador, BA, BrazilYale School of Public Health. New Haven, USAFundação Oswaldo Cruz. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilUniversidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilUniversidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador, BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilUniversidade Federal da Bahia. Faculdade de Medicina. Programa de Pós-graduação em Ciências da Saude. Salvador, BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilUniversidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brazil / King’s College Hospital. Harris Birthright Center for Fetal Medicine. London, UK / Universidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brazil / Escola Paulista de Medicina. São Paulo, SP, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilYale School of Public Health. New Haven, USA / Fundação Oswaldo Cruz. Salvador, BA, Brazil / Universidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador, BA, BrazilYale School of Public Health. New Haven, USAYale School of Public Health. New Haven, USA / Universidade Federal da Bahia. Salvador, BA, BrazilObjectives: To describe the differences in clinical presentation and relative disease burden of congenital Zika syndrome (CZS)-associated microcephaly at 2 large hospitals in Salvador, Brazil that serve patients of different socioeconomic status (SES). Methods: Clinical and serologic data were collected prospectively from pregnant women and their infants, who delivered at 2 study centers during the 2015–2016 Zika virus (ZIKV) epidemic in Salvador, Brazil. Results: Pregnant women from Salvador, Brazil delivering in a low SES hospital had 3 times higher ZIKV exposure rate than women at a high SES hospital. However, different SES hospitals had similar prevalence of infants with CZS-associated microcephaly (10% vs 6%, p = 0.16) after controlling for ZIKV exposure in their mothers. Conclusions: Our study supports the positive association between low SES, high maternal ZIKV exposure, and high rates of CZS-associated microcephaly

Risk of Zika microcephaly correlates with features of maternal antibodies

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-10T12:26:15Z No. of bitstreams: 1 Robbiani F D ...Risk.pdf: 2296966 bytes, checksum: 5e47aca9208f3f35c969fd82960279f4 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-10T13:32:42Z (GMT) No. of bitstreams: 1 Robbiani F D ...Risk.pdf: 2296966 bytes, checksum: 5e47aca9208f3f35c969fd82960279f4 (MD5)Made available in DSpace on 2019-10-10T13:32:42Z (GMT). No. of bitstreams: 1 Robbiani F D ...Risk.pdf: 2296966 bytes, checksum: 5e47aca9208f3f35c969fd82960279f4 (MD5) Previous issue date: 2019-01-07National Institutes of Health grants 5R01AI121207, R01TW009504, and R25TW009338 to A.I. Ko; National Institutes of Health pilot awards U19AI111825 and UL1TR001866 to D.F. Robbiani; National Institutes of Health grants R01AI037526, UM1AI100663, U19AI111825, UL1TR001866, and P01AI138938 to M.C. Nussenzweig; National Institutes of Health grants R01AI124690 and U19AI057229 (Cooperative Center for Human Immunology pilot project); The Rockefeller University Development Office and anonymous donors (to C.M. Rice); Fundação de Amparo `a Pesquisa do Estado da Bahia grant PET0021/2016 (to M.G. Reis); National Institutes of Health grant R21AI129479-Supplement (to K.K.A. Van Rompay) and the National Institutes of Health Office of Research Infrastructure Programs/OD (P51OD011107 to the CNPRC); the United States Food and Drug Administration contract HHSF223201610542P (to L.L. Coffey); National Institutes of Health grants R01AI100989 and R01AI133976 (to L. Rajagopal and K.M. Adams Waldorf); and National Institutes of Health grants AI083019 and AI104002 (to M. Gale Jr.) and grant P51OD010425 to the WaNPRC (to K.M. Adams Waldorf, J. Tisoncik-Go, and M. Gale Jr.). Studies at WNPRC were supported by DHHS/PHS/National Institutes of Health grant R01Al116382-01A1 (to D.H. O’Connor), in part by the National Institutes of Health Office of Research Infrastructure Programs/OD (grant P51OD011106) awarded toWNPRC, at a facility constructed in part with support from Research Facilities Improvement Programgrants RR15459-01 and RR020141-01; and National Institutes of Health core and pilot grant P51 OD011092 and grants R21-HD091032 and R01-HD08633 (to ONPRC). P.F.C. Vasconcelos was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (projects 303999/2016-0, 439971/20016-0, and 440405/2016-5) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Zika fast-track).The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA / Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven / Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.Fudan University. School of Basic Medical Sciences. Shanghai Medical College. Key Laboratory of Medical Molecular Virology. Shanghai, China.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil / Universidade Federal de São Paulo. São Paulo, SP, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA.Universidade Federal de São Paulo. São Paulo, SP, Brasil.Hospital Santo Amaro. Salvador, BA, Brasil.Hospital Santo Amaro. Salvador, BA, Brasil.Hospital Santo Amaro. Salvador, BA, Brasil.Hospital Aliança. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven / Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.University of California. California National Primate Research Center. Davis, Davis, CA, USA.University of California. School of Veterinary Medicine. Department of Pathology, Microbiology, and Immunology. Davis, Davis, CA, USA.Washington National Primate Research Center. Seattle, WA, USA / University of Washington. Center for Innate Immunity and Immune Disease. Seattle, WA, USA / University of Washington. Department of Immunology. Seattle, WA, USA.Washington National Primate Research Center. Seattle, WA / University of Washington. Center for Innate Immunity and Immune Disease. Seattle, WA, USA / University of Washington. Department of Immunology. Seattle, WA, USA / University of Washington. Department of Global Health. Seattle, WA, USA.University of Washington. Department of Global Health. Seattle, WA, USA / University of Washington. Department of Pediatrics. Seattle, WA, USA / Seattle Children’s Research Institute. Center for Global Infectious Disease Research. Seattle, WA, USA.Washington National Primate Research Center. Seattle, WA, USA / University of Washington. Center for Innate Immunity and Immune Disease. Seattle, WA, USA / University of Washington. Department of Global Health. Seattle, WA, USA / University of Washington. Department of Obstetrics and Gynecology. Seattle, WA, USA.University of Wisconsin-Madison. Department of Pathology and Laboratory Medicine. Madison, WI, USA.University of Wisconsin-Madison. Wisconsin National Primate Research Center. Madison, WI, USA.University of Wisconsin-Madison. Wisconsin National Primate Research Center. Madison, WI, USA.University of Wisconsin-Madison. Department of Pathology and Laboratory Medicine. Madison, WI, USA.Oregon National Primate Research Center. Division of Reproductive and Developmental Sciences. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Pathobiology and Immunology. Beaverton, OR, USA / Oregon Health and Science University. Vaccine and Gene Therapy Institute. Portland, OR, USA.Oregon Health and Science University. Vaccine and Gene Therapy Institute. Portland, OR, USA.Oregon National Primate Research Center. Pathology Services Unit, Division of Comparative Medicine. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Pathobiology and Immunology. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Reproductive and Developmental Sciences. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Reproductive and Developmental Sciences. Beaverton, OR, USA / Oregon Health and Science University. Department of Obstetrics and Gynecology. Portland, OR, USA.Oregon National Primate Research Center. Division of Reproductive and Developmental Sciences. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Pathobiology and Immunology. Beaverton, OR, USA / Oregon Health and Science University. Vaccine and Gene Therapy Institute. Portland, OR, USA.Oregon National Primate Research Center. Division of Pathobiology and Immunology. Beaverton, OR, USA / Oregon Health and Science University. Vaccine and Gene Therapy Institute. Portland, OR, USA.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.University of California. California National Primate Research Center. Davis, Davis, CA, USA / University of California. School of Veterinary Medicine. Department of Pathology, Microbiology, and Immunology. Davis, Davis, CA, USA.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, USA.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA / The Rockefeller University. Howard Hughes Medical Institute. New York, NY, USA.Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015-2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly