12 research outputs found
Infectious diseases, autoimmunity and midline defect in a patient with a novel bi-allelic mutation in IL12RB1 gene
No full textClinical disease caused by weakly pathogenic mycobacterial species, which is known as Mendelian susceptibility to mycobacterial disease (MSMD), is a rare entity. IFN-gamma and IL-17 production are defective due to insufficient response to IL-2 and IL-23 in IL-12R beta 1 deficiency; so this also causes tendency to intracellular microorganisms and candidal diseases. Here, we present a patient who suffers IL-12R beta 1 deficiency caused by a novel bi-allelic mutation with recurrent salmonellosis, mycobacterial, fungal infections and remained asymptomatic during 13 months of follow-up after hIFN-gamma treatment. In addition she had hemolytic anemia and midline defects like cleft lip and palate which have not been reported in a patient with MSMD in the literature prior to this case report. In conclusion, diagnosis of MSMD should be kept in mind in patients with recurrent salmonellosis, mycobacterial and fungal infections especially in countries with a high consanguinity rate.National Institute of Allergy and Infectious Diseases grant [5R01AI089970]; National Center for Research Resources; National Center for Advancing Sciences of the National Institutes of Health grant [8UL1TR000043]; Rockefeller University; St. Giles Foundation; Institut National de la Sante et de la Recherche Medicale (INSERM); Paris Descartes University; Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]; French National Research Agency.(ANR) under the Investments for the future [ANR-10-IAHU-01]We want to thank Yelena Nemirovskaya, and Lahouari Amar for their administrative support. This research was funded in part by the National Institute of Allergy and Infectious Diseases grant number 5R01AI089970, the National Center for Research Resources and the National Center for Advancing Sciences of the National Institutes of Health grant number 8UL1TR000043, The Rockefeller University, the St. Giles Foundation, Institut National de la Sante et de la Recherche Medicale (INSERM), Paris Descartes University, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID) and the French National Research Agency.(ANR) under the Investments for the future (grant number ANR-10-IAHU-01)
TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons
No full textHuman herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. Tlr3-/- mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-β secretion and ISG mRNA in induced pluripotent stem cell-derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-β immunity.sponsorship: We thank the patients and their families for their participation. We thank the members of both branches of the St. Giles Laboratory of Human Genetics of Infectious Diseases, in particular Tatiana Kochetkov, for expertise and assistance with cell culture, Dusan Bogunovic for invaluable discussions and advice, and Dominick Papandrea, Cecile Patissier, and Yelena Nemirovskaya for administrative assistance. We thank Pierre Lebon (Laboratory of Virology, Paris University, Assistance Publique-Hopitaux de Paris, Cochin Hospital) for providing us with VSV and technical advice. This work was funded in part by the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1TR001866), NIH (R01NS072381, R01AI088364, and R21AI151663), the French National Research Agency (ANR) under the "Investments for the future" program (ANR-10-IAHU-01), Integrative Biology of Emerging Infectious Diseases Laboratoire d'Excellence (ANR-10-LABX-62-IBEID), and grants ANR-14-CE14-0008-01 and ANR-18-CE15-0020-02, The Rockefeller University, Institut National de la Sante et de la Recherche Medicale (INSERM), Paris Descartes University, and the St. Giles Foundation. DG is supported by the Charles H. Revson Senior Fellowship in Biomedical Sciences and the National Natural Science Foundation of China (grant 319708550). IM is supported by KU Leuven C1 grant C16/18/007 and Fonds Wetenschappelijk Onderzoek Vlaanderen grant G0C8517N. (National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program|UL1TR001866, NIH|R01NS072381, NIH|R01AI088364, NIH|R21AI151663, French National Research Agency (ANR)|ANR-10-IAHU-01, French National Research Agency (ANR)|ANR-10-LABX-62-IBEID, French National Research Agency (ANR)|ANR-14-CE14-0008-01, French National Research Agency (ANR)|ANR-18-CE15-0020-02, Rockefeller University, Institut National de la Sante et de la Recherche Medicale (INSERM), Paris Descartes University, St. Giles Foundation, Charles H. Revson Senior Fellowship in Biomedical Sciences, National Natural Science Foundation of China|319708550, KU Leuven|C16/18/007, Fonds Wetenschappelijk Onderzoek Vlaanderen|G0C8517N, FLF|MR/S032304/1, Medical Research Foundation|C0483, National Institute of Allergy and Infectious Diseases|R21AI151663)status: Publishe
Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated <i>RPSA</i> exons
No full textIsolated congenital asplenia (ICA) is the only known human developmental defect exclusively affecting a lymphoid organ. In 2013, we showed that private deleterious mutations in the protein-coding region of RPSA, encoding ribosomal protein SA, caused ICA by haploinsufficiency with complete penetrance. We reported seven heterozygous protein-coding mutations in 8 of the 23 kindreds studied, including 6 of the 8 multiplex kindreds. We have since enrolled 33 new kindreds, 5 of which are multiplex. We describe here 11 new heterozygous ICA-causing RPSA protein-coding mutations, and the first two mutations in the 5'-UTR of this gene, which disrupt mRNA splicing. Overall, 40 of the 73 ICA patients (55%) and 23 of the 56 kindreds (41%) carry mutations located in translated or untranslated exons of RPSA. Eleven of the 43 kindreds affected by sporadic disease (26%) carry RPSA mutations, whereas 12 of the 13 multiplex kindreds (92%) carry RPSA mutations. We also report that 6 of 18 (33%) protein-coding mutations and the two (100%) 5'-UTR mutations display incomplete penetrance. Three mutations were identified in two independent kindreds, due to a hotspot or a founder effect. Finally, RPSA ICA-causing mutations were demonstrated to be de novo in 7 of the 23 probands. Mutations in RPSA exons can affect the translated or untranslated regions and can underlie ICA with complete or incomplete penetrance.sponsorship: We thank the patients and all of their families. Many of the new families in this study contacted us directly and devoted considerable effort and time to their participation in this study. We also thank Yelena Nemirovskaya, Dominick Papandrea, David Hum, Cecile Patissier, Benedetta Bigio, and Maya Chrabieh, who helped with all of the administrative questions and tasks required for this study. This work was supported in part by March of Dimes Grant 1-FY12-440, St. Giles Foundation, National Center for Research Resources and the National Center for Advancing Sciences of the National Institutes of Health Grant 8UL1 TR001866, the French National Agency for Research under the "Investissement d'avenir" program Grant ANR-10-IAHU-01, and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence Grant ANR-10-LABX-62-IBEID. A.B. was funded by a fellowship from the Jane Coffin Childs Memorial Fund for Medical Research from July 2014 to November 2015. B. Bosch was supported by a fellowship from the Boehringer Ingelheim Fonds. (March of Dimes Grant|1-FY12-440, St. Giles Foundation, National Center for Research Resources, National Center for Advancing Sciences of the National Institutes of Health|8UL1 TR001866, French National Agency for Research under "Investissement d'avenir" program|ANR-10-IAHU-01, Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence|ANR-10-LABX-62-IBEID, Jane Coffin Childs Memorial Fund for Medical Research, Boehringer Ingelheim Fonds)status: Publishe
Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency
No full textInborn errors of TLR3-dependent IFN-α/β- and IFN-λ-mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions of IFN-α/β and IFN-λ are unknown. We report a child homozygous for a genomic deletion of the entire coding sequence and part of the 3'-UTR of the last exon of IFNAR1, who died of HSE at the age of 2 years. An older cousin died following vaccination against measles, mumps, and rubella at 12 months of age, and another 17-year-old cousin homozygous for the same variant has had other, less severe, viral illnesses. The encoded IFNAR1 protein is expressed on the cell surface but is truncated and cannot interact with the tyrosine kinase TYK2. The patient's fibroblasts and EBV-B cells did not respond to IFN-α2b or IFN-β, in terms of STAT1, STAT2, and STAT3 phosphorylation or the genome-wide induction of IFN-stimulated genes. The patient's fibroblasts were susceptible to viruses, including HSV-1, even in the presence of exogenous IFN-α2b or IFN-β. HSE is therefore a consequence of inherited complete IFNAR1 deficiency. This viral disease occurred in natural conditions, unlike those previously reported in other patients with IFNAR1 or IFNAR2 deficiency. This experiment of nature indicates that IFN-α/β are essential for anti-HSV-1 immunity in the CNS.sponsorship: We warmly thank our patients and their families. We thank the members of both branches of the Laboratory of Human Genetics of Infectious Diseases for helpful discussions; Tatiana Kochetkov for technical assistance; Dominick Papandrea, Cecile Patissier, and Yelena Nemirovskaya for administrative assistance; Mahbuba Rahman, Fatima Al Ali, and Manar Ata for help with VirScan data analysis; and Stephen Elledge (Brigham and Women's Hospital, Harvard Medical School) for providing the VirScan phage library that was used in this study for antibody profiling in the patient and controls. This work was conducted in the 2 branches of the Laboratory of Human Genetics of Infectious Diseases, and was funded in part by the National Center for Advancing Translational Sciences/NIH/Clinical and Translational Science Award program (grant UL1TR001866); NIH grants R01AI088364, R01NS072381, and R21AI151663; National Vaccine Program Office of the US Department of Health and Human Services grant VSRNV000006; grants from the Integrative Biology of Emerging Infectious Diseases Laboratory ofExcellence(ANR-10-LABX-62-IBEID) and the French National Research Agency (ANR) under the "Investments for the future" program (ANR-10-IAHU-01); ANR grants IEIHSEER (ANR14-CE14-0008-01), SEAeHostFactors (ANR-18-CE15-0020-02), and CNSVIRGEN (ANR-19-CE15-0009-01); the French Foundation for Medical Research (FRM) (EQU201903007798); the Qatar National Research Fund (NPRP9-251-3-045); Rockefeller University; INSERM; University of Paris; and the St. Giles Foundation. PB was supported by the FRM (EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). JR was supported by the INSERM PhD program ("poste d'accueil Inserm"). JM was supported by ANR grants BURULIGEN (ANR-12-BSV3-0013-01) and MYCOPARADOX (ANR-16-CE12-0023). IM is a senior clinical investigator at the Fonds Wetenschappelijk Onderzoek (FWO) Vlaanderen and is supported by FWO grant G0C8517N. (National Center for Advancing Translational Sciences/NIH/Clinical and Translational Science Award program|UL1TR001866, NIH|R01AI088364, NIH|R01NS072381, NIH|R21AI151663, National Vaccine Program Office of the US Department of Health and Human Services|VSRNV000006, French National Research Agency (ANR) under the "Investments for the future" program|ANR-10-IAHU-01, ANR|ANR14-CE14-0008-01, ANR|ANR-18-CE15-0020-02, ANR|ANR-19-CE15-0009-01, ANR|ANR-12-BSV3-0013-01, ANR|ANR-16-CE12-0023, French Foundation for Medical Research (FRM)|EQU201903007798, Qatar National Research Fund|NPRP9-251-3-045, Rockefeller University, INSERM, University of Paris, St. Giles Foundation, FRM|EA20170638020, MD-PhD program of the Imagine Institute (Fondation Bettencourt-Schueller), INSERM PhD program ("poste d'accueil Inserm"), FWO|G0C8517N, Integrative Biology of Emerging Infectious Diseases Laboratory ofExcellence|ANR-10-LABX-62-IBEID, Agence Nationale de la Recherche (ANR)|ANR-12-BSV3-0013, Agence Nationale de la Recherche (ANR)|ANR-18-CE15-0020, Agence Nationale de la Recherche (ANR)|ANR-19-CE15-0009, Agence Nationale de la Recherche (ANR)|ANR-16-CE12-0023, National Institute of Allergy and Infectious Diseases|R21AI151663)status: Publishe
Inherited p40<i><SUP>phox</SUP></i> deficiency differs from classic chronic granulomatous disease
No full textBiallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.sponsorship: The authors thank all the patients and their relatives as well as the treatment teams for their participation in this study. We also thank Celine Desvallees, Dominick Papandrea, Cecile Patissier, and Yelena Nemirovskaya at the HGMI laboratory (Rockefeller University branch) and the Institute Imagine branch for administrative assistance. We thank all the members of the Blood Cell Research Department and the HGMI Laboratory for helpful discussions. We acknowledge the use of the biological resources of the Imagine Institute DNA-Biobank (BB-33-00065). AVDG was supported by the Sanquin Blood Supply Product and Process Development Cellular Products Fund (PPOC 1957). ANP was supported by the CONACYT National PhD Fellowship Program. The HGMI Laboratory was funded in part by the NIAID (5R01AI089970 and 5R37AI095983), the National Center for Research Resources, and the National Center for Advancing Sciences of the NIH (8UL1TR000043), The Rockefeller University, the St. Giles Foundation, INSERM, Paris Descartes University, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), and the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10IAHU-01, to the Imagine Institute), ANR-IFNPHOX/ANR-13-ISV3-0001-01, and ANR-GENMS-MD/ANR-16-CE17-0005-01 (to JB), ECOSNord-C14S01 (to JB and JLF), and COLCIENCIAS (576-2013: 111556934990, to JLF). KM was supported by a Japan Foundation for Pediatric Research fellowship grant. AMM was funded by the Canadian Institutes of Health Research (CIHR) and The Leona M. and Harry B. Helmsley Charitable Trust. This work was supported in part by the Division of Intramural Research, NIAID, NIH and was funded in part with federal funds from the National Cancer Institute, NIH (HHSN261200800001E). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. (Imagine Institute DNA-Biobank|BB-33-00065, Sanquin Blood Supply Product and Process Development Cellular Products Fund|PPOC 1957, CONACYT National PhD Fellowship Program, NIAID|5R01AI089970, NIAID|5R37AI095983, National Center for Research Resources, National Center for Advancing Sciences of the NIH|8UL1TR000043, Rockefeller University, St. Giles Foundation, INSERM, Paris Descartes University, Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence|ANR-10-LABX-62-IBEID, French National Research Agency (ANR) under the "Investments for the Future" program|ANR-10IAHU-01, French National Research Agency (ANR)|ANR-IFNPHOX/ANR-13-ISV3-0001-01, French National Research Agency (ANR)|ANR-GENMS-MD/ANR-16-CE17-0005-01, COLCIENCIAS|576-2013: 111556934990, Japan Foundation for Pediatric Research fellowship grant, Canadian Institutes of Health Research (CIHR), Leona M. and Harry B. Helmsley Charitable Trust, Division of Intramural Research, NIAID, NIH, National Cancer Institute, NIH|HHSN261200800001E, ECOSNord-C14S01)status: Publishe
Inherited human ITK deficiency impairs IFN-? immunity and underlies tuberculosis
No full textInborn errors of IFN-gamma immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4(+) alpha beta T lymphocytopenia with a concomitant expansion of CD4(-)CD8(-) double-negative (DN) alpha beta and V delta 2(-) gamma delta T lymphocytes, both displaying a unique CD38(+)CD45RA(+)T-bet(+)EOMES(-) phenotype. Itk-deficient mice recapitulated an expansion of the gamma delta T and DN alpha beta T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-gamma in response to TCR crosslinking, mitogens, or forced synapse formation with autologous B lymphocytes. Finally, the patients' total lymphocytes secrete small amounts of IFN-gamma, and CD4(+), CD8(+), DN alpha beta T, V delta 2(+) gamma delta T, and MAIT cells display impaired IFN-gamma production in response to BCG. Inherited ITK deficiency undermines the development and function of various IFN-gamma-producing T cell subsets, thereby underlying TB.Empire State Stem Cell Fund for providing support through NYSDOH [RRID:SCR_017694]; NIH [C023046]; Harvard University Medical School; St. Giles Foundation; Institut National de la Sante et de la Recherche Medicale (INSERM), University of Paris, Sidra Medicine [SDR400048]; National Institute of Allergy and Infectious Diseases; National Center for Research Resources [R01AI095983, U19AI162568, U19AI142737]; National Center for Advancing Sciences of the National Institutes of Health [UL1TR001866]; French National Research Agency under the Investments for the Future program; Agence Nationale de Recherches sur le Sida et les Hepatites Virales project [ANR-10-IAHU-01, ANR-10-LABX-62-IBEID]; French Foundation for Medical Research [ECTZ170784-ANRS0073]; SCOR Corporate Foundation for Science [EQU201903007798]; David Rockefeller Graduate Program; Funai Foundation for Information Technology; Honjo International Scholarship Foundation; National Cancer Institute F99 Award [F99CA274708]; Immune Deficiency Foundation; Stony Wold-Herbert Fund; Ministerio de Ciencia Tecnologia e Innovacion MINCIENCIAS, Colombia [111574455633/CT 713-2016, 111584467551/CT 415-2020, CT 806-2018/046-2019]; Comite para el Desarrollo de la Investigacion, CODI-Universidad de Antioquia, Colombia; Care-for-Rare Foundation [CT 2017-16003]; Else Kroner-Fresenius Stiftung [160073]; German Federal Ministry of Education and Research [2017_A110]; Rockefeller University [01GM1910C]We would like to thank the patients, their relatives, and their physicians for participating in this study; Erin Williams, Dominick Papandrea, Yelena Nemirovskaya, Dana Liu, Mark Woollett, Lazaro Lorenzo, and Cecile Patissier for administrative assistance; Tatiana Kochetkov for technical assistance; the members of the laboratory for helpful discussions. We thank the Flow Cytometry Resource Center at The Rockefeller University (RRID:SCR_017694), and the Empire State Stem Cell Fund for providing support through NYSDOH Contract #C023046. We thank the NIH Tetramer Core Facility (NTCF) for providing the 5-OP-RU-loaded MR1 tetramer and PBS-57-loaded CD1d tetramer, which were developed jointly with Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie. We thank Stephen Elledge (Brigham and Women's Hospital, Harvard University Medical School, Boston, MA) for kindly providing the VirScan phage library.; The study was supported in part by a grant from the St. Giles Foundation, The Rockefeller University, Institut National de la Sante et de la Recherche Medicale (INSERM), University of Paris, Sidra Medicine (SDR400048), the National Institute of Allergy and Infectious Diseases (R01AI095983 and U19AI162568 to J.-L. Casanova and U19AI142737 to S. Boisson-Dupuis), the National Center for Research Resources, the National Center for Advancing Sciences of the National Institutes of Health (UL1TR001866), the French National Research Agency under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), Agence Nationale de Recherches sur le Sida et les Hepatites Virales project ECTZ170784-ANRS0073 (grant awarded to S. Boisson-Dupuis), the French Foundation for Medical Research (EQU201903007798), the SCOR Corporate Foundation for Science, and funding from the intramural program of the National Institute of Allergy and Infectious Diseases to P.L. Schwartzberg, D.P. Golec, and Z. Kaul. M. Ogishi was supported by the David Rockefeller Graduate Program, the New York Hideyo Noguchi Memorial Society, the Funai Foundation for Information Technology, the Honjo International Scholarship Foundation, and the National Cancer Institute F99 Award (F99CA274708). R. Yang was supported by the Immune Deficiency Foundation and the Stony Wold-Herbert Fund. A.A. Arias was supported by the Ministerio de Ciencia Tecnologia e Innovacion MINCIENCIAS, Colombia (111574455633/CT 713-2016 and 111584467551/CT 415-2020), Movilidad Academica ECOS-Nord/MINCIENCIAS, Colombia (CT 806-2018/046-2019) and Comite para el Desarrollo de la Investigacion, CODI-Universidad de Antioquia, Colombia (CT 2017-16003). F. Hauck was supported by the Care-for-Rare Foundation (160073), the Else Kroner-Fresenius Stiftung (2017_A110), and the German Federal Ministry of Education and Research (01GM1910C). Open Access funding provided by Rockefeller University
Proceedings of the Workshop on the Okhotsk Sea and Adjacent Areas [Vladivostok, June 1995]
No full textI REPORT OF THE PICES WORKSHOP ON THE OKHOTSK SEA AND ADJACENT AREAS (pdf, 0.1 Mb)
1. Outline of the workshop
2. Summary reports from sessions
3. Recommendations of the workshop
4. Acknowledgments
II SCIENTIFIC PAPERS SUBMITTED FROM SESSIONS
1. Physical Oceanography Sessions (pdf, 4 Mb)
A. Circulation and water mass structure of the Okhotsk Sea and Northwestern Pacific
Valentina D. Budaeva & Vyacheslav G. Makarov
Seasonal variability of the pycnocline in La Perouse Strait and Aniva Gulf
Valentina D. Budaeva & Vyacheslav G. Makarov
Modeling of the typical water circulations in the La Perouse Strait and Aniva Gulf region
Nina A. Dashko, Sergey M. Varlamov, Young-Ho Han & Young-Seup Kim
Anticyclogenesis over the Okhotsk Sea and its influence on weather
Boris S. Dyakov, Alexander A. Nikitin & Vadim P. Pavlychev
Research of water structure and dynamics in the Okhotsk Sea and adjacent Pacific
Howard J. Freeland, Alexander S. Bychkov, C.S. Wong, Frank A. Whitney & Gennady I. Yurasov
The Ohkotsk Sea component of Pacific Intermediate Water
Emil E. Herbeck, Anatoly I. Alexanin, Igor A. Gontcharenko, Igor I. Gorin, Yury V. Naumkin & Yury G. Proshjants
Some experience of the satellite environmental support of marine expeditions at the Far East Seas
Alexander A. Karnaukhov
The tidal influence on the Sakhalin shelf hydrology
Yasuhiro Kawasaki
On the formation process of the subsurface mixed water around the Central Kuril Islands
Lloyd D. Keigwin
Northwest Pacific paleohydrography
Talgat R. Kilmatov
Physical mechanisms for the North Pacific Intermediate Water formation
Vladimir A. Luchin
Water masses in the Okhotsk Sea
Andrey V. Martynov, Elena N. Golubeva & Victor I. Kuzin
Numerical experiments with finite element model of the Okhotsk Sea circulation
Nikolay A. Maximenko, Anatoly I. Kharlamov & Raissa I. Gouskina
Structure of Intermediate Water layer in the Northwest Pacific
Nikolay A. Maximenko & Andrey Yu. Shcherbina
Fine-structure of the North Pacific Intermediate Water layer
Renat D. Medjitov & Boris I. Reznikov
An experimental study of water transport through the Straits of Okhotsk Sea by electromagnetic method
Valentina V. Moroz
Oceanological zoning of the Kuril Islands area in the spring-summer period
Yutaka Nagata
Note on the salinity balance in the Okhotsk Sea
Alexander D. Nelezin
Variability of the Kuroshio Front in 1965-1991
Vladimir I. Ponomarev, Evgeny P. Varlaty & Mikhail Yu. Cheranyev
An experimental study of currents in the near-Kuril region of the Pacific Ocean and in the Okhotsk Sea
Stephen C. Riser, Gennady I. Yurasov & Mark J. Warner
Hydrographic and tracer measurements of the water mass structure and transport in the Okhotsk Sea in early spring
Konstantin A. Rogachev & Andrey V. Verkhunov
Circulation and water mass structure in the southern Okhotsk Sea, as observed in summer, 1994
Lynne D. Talley
North Pacific Intermediate Water formation and the role of the Okhotsk Sea
Anatoly S. Vasiliev & Fedor F. Khrapchenkov
Seasonal variability of integral water circulation in the Okhotsk Sea
B. Sea ice and its relation to circulation and climate
V.P. Gavrilo, G.A. Lebedev & A.P. Polyakov
Acoustic methods in sea ice dynamics studies
Nina M. Pestereva & Larisa A. Starodubtseva
The role of the Far-East atmospheric circulation in the formation of the ice cover in the Okhotsk Sea
Yoshihiko Sekine
Anomalous Oyashio intrusion and its teleconnection with Subarctic North Pacific circulation, sea ice of the Okhotsk Sea and air temperature of the northern Asian continent
C. Waves and tides
Vladimir A. Luchin
Characteristics of the tidal motions in the Kuril Straits
George V. Shevtchenko
On seasonal variability of tidal constants in the northwestern part of the Okhotsk Sea
D. Physical oceanography of the Japan Sea/East Sea
Mikhail A. Danchenkov, Kuh Kim, Igor A. Goncharenko & Young-Gyu Kim
A “chimney” of cold salt waters near Vladivostok
Christopher N.K. Mooers & Hee Sook Kang
Preliminary results from a numerical circulation model of the Japan Sea
Lev P. Yakunin
Influence of ice production on the deep water formation in the Japan Sea
2. Fisheries and Biology Sessions (pdf, 2.8 Mb)
A. Communities of the Okhotsk Sea and adjacent waters: composition, structure and dynamics
Lubov A. Balkonskaya
Exogenous succession of the southwestern Sakhalin algal communities
Tatyana A. Belan, Yelena V. Oleynik, Alexander V. Tkalin & Tat’yana S. Lishavskaya
Characteristics of pelagic and benthic communities on the North Sakhalin Island shelf
Lev N. Bocharov & Vladimir K. Ozyorin
Fishery and oceanographic database of Okhotsk Sea
Victor V. Lapko
Interannual dynamics of the epipelagic ichthyocen structure in the Okhotsk Sea
Valentina I. Lapshina
Quantitative seasonal and year-to-year changes of phytoplankton in the Okhotsk Sea and off Kuril area of the Pacific
Lyudmila N. Luchsheva
Biological productivity in anomalous mercury conditions (northern part of Okhotsk Sea)
Inna A. Nemirovskaya
Origin of hydrocarbons in the ecosystems of coastal region of the Okhotsk Sea
Tatyana A. Shatilina
Elements of the Pacific South Kuril area ecosystem
Vyacheslav P. Shuntov & Yelena P. Dulepova
Biota of the Okhotsk Sea: Structure of communities, the interannual dynamics and current status
B. Abundance, distribution, dynamics of the common fishes of the Okhotsk Sea
Yuri P. Diakov
Influence of some abiotic factors on spatial population dynamics of the West Kamchatka flounders (Pleuronectidae)
Gordon A. McFarlane, Richard J. Beamish & Larisa M. Zverkova
An examination of age estimates of walleye pollock (Theragra chalcogramma) from the Sea of Okhotsk using the burnt otolith method and implications for stock assessment and management
Larisa P. Nikolenko
Migration of Greenland turbot (Reinhardtius hippoglossoides) in the Okhotsk Sea
Galina M. Pushnikova
Fisheries impact on the Sakhalin-Hokkaido herring population
Vidar G. Wespestad
Is pollock overfished?
C. Salmon of the Okhotsk Sea: biology, abundance and stock identification
Vladimir A. Belyaev, Alexander Yu. Zhigalin
Epipelagic Far Eastern sardine of the Okhotsk Sea
Yuri E. Bregman, Victor V. Pushnikov, Lyudmila G. Sedova & Vladimir Ph. Ivanov
A preliminary report on stock status and productive capacity of horsehair crab Erimacrus isenbeckii (Brandt) in the South Kuril Strait
Natalia T. Dolganova
Mezoplankton distribution in the West Japan Sea
Vladimir V. Efremov, Richard L. Wilmot, Christine M. Kondzela, Natalia V. Varnavskaya, Sharon L. Hawkins & Maria E. Malinina
Application of pink and chum salmon genetic baseline to fishery management
Vyacheslav N. Ivankov & Valentina V. Andreyeva
Strategy for culture, breeding and numerous dynamics of Sakhalin salmon populations
Alla M. Kovalevskaya, Natalia I. Savelyeva & Dmitry M. Polyakov
Primary production in Sakhalin shelf waters
Tatyana N. Krupnova
Some reasons for resource reduction of Laminaria japonica (Primorye region)
Lyudmila N. Luchsheva & Anatoliy I. Botsul
Mercury in bottom sediments of the northeastern Okhotsk Sea
Pavel A. Luk’yanov, Natalia I. Belogortseva, Alexander A. Bulgakov, Alexander A. Kurika & Olga D. Novikova
Lectins and glycosidases from marine macro and micro-organisms of Japan and Okhotsk Seas
Boris A. Malyarchuk, Olga A. Radchenko, Miroslava V. Derenko, Andrey G. Lapinski & Leonid L. Solovenchuk
PCR-fingerprinting of mitochondrial genome of chum salmon, Oncorhynchus keta
Alexander A. Mikheev
Chaos and relaxation in dynamics of the pink salmon (Oncorhynchus gorbuscha) returns for two regions
Yuri A. Mitrofanov & Larisa N. Lesnikova
Fish-culture of Pacific Salmons increases the number of heredity defects
Larisa P. Nikolenko
Abundance of young halibut along the West Kamchatka shelf in 1982-1992
Sergey A. Nizyaev
Living conditions of golden king crab Lithodes aequispina in the Okhotsk Sea and near the Kuril Islands
Ludmila A. Pozdnyakova & Alla V. Silina
Settlements of Japanese scallop in Reid Pallada Bay (Sea of Japan)
Galina M. Pushnikova
Features of the Southwest Okhotsk Sea herring
Vladimir I. Radchenko & Igor I. Glebov
Present state of the Okhotsk herring stock and fisheries outlook
Alla V. Silina & Ida I. Ovsyannikova
Distribution of the barnacle Balanus rostratus eurostratus near the coasts of Primorye (Sea of Japan)
Galina I. Victorovskaya
Dependence of urchin Strongylocentrotus intermedius reproduction on water temperature
Anatoly F. Volkov, Alexander Y. Efimkin & Valery I. Chuchukalo
Feeding habits of Pacific salmon in the Sea of Okhotsk and in the Pacific waters of Kuril Islands in summer 1993
Larisa M. Zverkova & Georgy A. Oktyabrsky
Okhotsk Sea walleye pollock stock status
Tatyana N. Zvyagintseva, Elena V. Sundukova, Natalia M. Shevchenko & Ludmila A. Elyakova
Water soluble polysaccharides of some Far-Eastern seaweeds
3. Biodiversity Program (pdf, 0.2 Mb)
A. Biodiversity of island ecosystems and seasides of the North Pacific
Larissa A. Gayko
Productivity of Japanese scallop Patinopecten yessoensis (IAY) culture in Posieta Bay (Sea of Japan)
III APPENDICES
1. List of acronyms
2. List of participants
(Document pdf contains 431 pages
Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
No full textX-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.sponsorship: We thank the patients and their families for placing their trust in us. We warmly thank A. Dominguez-Acosta, P. Santana-Falcon, E. Rodriguez-Gonzalez, and M.E. Rosales-Bordon for technical assistance, and Y. Nemirovskaya, M. Woollett, D. Liu, S. Boucherit, C. Rivalain, M. Chrabieh and L. Lorenzo for administrative assistance. We are indebted to the "Biobanc de l'Hospital Infantil Sant Joan de Deu per a la Investigacio" for sample and data procurement and "Kids Corona Platform" Hospital Sant Joan de Deu, Barcelona. We would like to thank the members of the International IPF Genetics Consortium (https://github.com/genomicsITER/PFgenetics) for granting access to the genome-wide association studies summary data in the study across five cohorts, and to J.M. Aznar for providing data about mutations in RTEL1 in Spanish patients with IEI. We thank Erin Williams for organizing the logistics of patient samples and whole-exome sequencing. The graphical abstract was created with BioRender.com. The study was funded by Instituto de Salud Carlos III (COV20_01333, COV20_01334, PI16/00759, PI18/00223, PI19/00208, PI20/00876, and PI21/00211), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER), the Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias (FIISC19/43 and FIISC22/27), Grupo DISA (OA18/017 and OA22/035), Fundacion MAPFRE Guanarteme (OA21/131), Cabildo Insular de Tenerife (CGIEU0000219140 and "Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19"), a 2022 Convocatoria de Beques de Recerca IRSJD-Carmen de Torres 2022 (2022AR-IRSJD-CdTorres), CERCA Programme/Generalitat de Catalunya, the Else Kroener-Fresenius Stiftung (EKFS, 2017_A110), the German Federal Ministry of Education and Research (01GM1910C), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Horizon Europe Framework Programme of the European Union under Grant Agreement no. 101057100. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. (Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation|COV20_01333, Spanish Ministry of Science and Innovation|COV20_01334, Spanish Ministry of Science and Innovation|PI16/00759, Spanish Ministry of Science and Innovation|PI18/00223, Spanish Ministry of Science and Innovation|PI19/00208, Spanish Ministry of Science and Innovation|PI20/00876, Spanish Ministry of Science and Innovation|PI21/00211, Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias|RTC-2017-6471-1, Grupo DISA|FIISC19/43, Grupo DISA|FIISC22/27, Fundacion MAPFRE Guanarteme|OA18/017, Fundacion MAPFRE Guanarteme|OA22/035, Cabildo Insular de Tenerife|OA21/131, 2022 Convocatoria de Beques de Recerca IRSJD-Carmen de Torres 2022|CGIEU0000219140, CERCA Programme/Generalitat de Catalunya|2022AR-IRSJD-CdTorres, Else Kroener-Fresenius Stiftung (EKFS), German Federal Ministry of Education and Research|2017_A110, Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health|01GM1910C, Horizon Europe Framework Programme of the European Union, 101057100, National Institute of Allergy and Infectious Diseases|R01AI163029, National Institute of Allergy and Infectious Diseases|R01AI088364, National Institute of Allergy and Infectious Diseases|ZIAAI001265, National Institute of Allergy and Infectious Diseases|ZIAAI001270)status: Publishe
Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria
No full textHuman inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ
"Arising from the depths" (Kupala) : a study of Belarusian literature in English translation
No full textUsing Belarusian as a case study of a ‘minority’ European literature, this thesis
explores the role of literary translation in the negotiation and promotion of a national
identity (represented by two opposing discourses of “Old/European” and “New/Soviet”
‘Belarusianness’) as accomplished through translation from a lesser-known European
tongue into the current global hegemonic language. In so doing, the research provides a
wide historical panorama of all known literary translations from Belarusian to English,
focusing on those published in the 20th and 21st centuries. While outlining the major
tendencies of the translation process, the study considers the issues of both reception
(focusing on the TL literary system) and representation (focusing on the negotiation of a
Belarusian identity), recognising complex ideological, historical and political processes
which accompany and, in many cases, predetermine translations and translation
strategies.
After examining the available terminology for the description of ‘minority’ in
literary theory and translation studies, this research considers Belarus’ position as an
Eastern European, post-Soviet country and discusses the case for the adoption of a
postcolonial approach to the interpretation of ‘Belarusianness’. Another innovative aspect
of the study lies in the contribution of a non-Western perspective to the current discussion
of European minority languages in translation studies (Baer 2011; Branchadell and West
2005; Cronin 1995, 2003; Tymoczko 1995, 1999).
A pioneering work on the history of Belarusian-English literary translation, this
research defines several periods of translation activities: the ‘early’ translations of the
1890s – 1940s which mark the discovery of Belarusian folklore; the translations of the
‘Cold War’ period (1950s – 1980s) with two opposing ‘camps’ producing works
provoked by nationalist (Western-based translations) or socialist (Soviet Union)
ideologies; and, finally, the current post-independence period of Belarusian-English
translation (1991-2012), with an analysis of the reasons for a relative inactivity. The
evidence is based on a wide range of translations published as individual books and
anthologies of poetry and prose, as well as those found in periodicals. It also includes
previously unpublished findings from materials located in personal and national archives
in Russia, Belarus, and the UK
