Relevant bibliographies by topics / Genomic HLA

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  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
  5. Conference papers
  6. Reports

Academic literature on the topic 'Genomic HLA'

Author: Grafiati
Published: 31 May 2023

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Journal articles on the topic "Genomic HLA"

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Amar, A., G. T. Nepom, E. Mickelson, H. Erlich, and J. A. Hansen. "HLA-DP and HLA-DO genes in presumptive HLA-identical siblings: structural and functional identification of allelic variation." Journal of Immunology 138, no. 6 (March 15, 1987): 1947–53. http://dx.doi.org/10.4049/jimmunol.138.6.1947.

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Abstract We analyzed HLA class II genomic polymorphisms in three families in which bone marrow transplantation was performed between individuals presumed to be HLA identical, but in which unexplained mixed lymphocyte culture reactivity was observed. These families were characterized by classical HLA serology, MLC, and DP typing. In each family, a pair of "HLA-identical" siblings demonstrated a small proliferative response in bidirectional MLC. Southern blotting analysis performed with cDNA probes for DQ alpha, DP alpha, and DP beta identified DP genomic differences in each case. Hybridization of Bgl II-digested genomic DNA with a DP alpha cDNA probe revealed three prominent polymorphic fragments (7.7, 5.8, and 3.7 kb), which discriminated between presumptive identical siblings and indicated crossover events within HLA. Similarly, hybridization of SstI-digested genomic DNA with a DP beta cDNA probe, although resulting in a more complex pattern, identified DP genomic disparity between the presumed HLA identical siblings. Hybridization of SstI-digested DNA from two families with evidence of DP recombination was performed by using an oligonucleotide probe specific for the newly described HLA class II gene DO beta. Two major polymorphic fragments, at 6.2 and 3.3 kb, segregated in these families and localized the crossovers flanking the DO beta gene between the DQ and DP loci. The contribution of the antigenic differences marked by these HLA DP and DO DNA polymorphisms to allorecognition in MLR and in graft-vs-host disease are discussed.
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Meyer, Diogo, Vitor R. C. Aguiar, Bárbara D. Bitarello, Débora Y. C. Brandt, and Kelly Nunes. "A genomic perspective on HLA evolution." Immunogenetics 70, no. 1 (July 7, 2017): 5–27. http://dx.doi.org/10.1007/s00251-017-1017-3.

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Drover, Sheila, and William H. Marshall. "Transfection of HLA genes using genomic DNA." Human Immunology 31, no. 4 (August 1991): 293–98. http://dx.doi.org/10.1016/0198-8859(91)90102-f.

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Hansen, H. E., L. O. Vejerslev, and S. Olesen Larsen. "Hydatidiform mole and HLA. III. HLA-antigen expression related to genomic origin." Tissue Antigens 32, no. 3 (September 1988): 162–69. http://dx.doi.org/10.1111/j.1399-0039.1988.tb01653.x.

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Pei, Ji, S. Yoon Choo, Thomas Spies, Jack L. Strominger, and John A. Hansen. "Association of four HLA class III region genomic markers with HLA haplotypes." Tissue Antigens 37, no. 5 (May 1991): 191–96. http://dx.doi.org/10.1111/j.1399-0039.1991.tb01871.x.

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Balas, A., D. Planelles, M. Rodríguez-Cebriá, N. Puig, and J. L. Vicario. "Genomic sequences of HLA-A*68:169, HLA-B*07:298 and HLA-B*39:129." International Journal of Immunogenetics 45, no. 3 (March 8, 2018): 140–42. http://dx.doi.org/10.1111/iji.12360.

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D'Amato, Mauro, Rosa Sorrentino, and Roberto Tosi. "Extremely simplified sample preparation for HLA genomic typing." Tissue Antigens 39, no. 1 (January 1992): 40–41. http://dx.doi.org/10.1111/j.1399-0039.1992.tb02156.x.

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Yamashita, T., K. Tokunaga, K. Tadokoro, T. Juji, and Y. Taketanl. "Correction of the HLA-G*01012 genomic sequence." Tissue Antigens 49, no. 6 (June 1997): 673–74. http://dx.doi.org/10.1111/j.1399-0039.1997.tb02823.x.

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Geraphty, Daniel E., Marta Janer, and Thierry Guillaudeux. "Genomic sequencing of the HLA class I region." Human Immunology 47, no. 1-2 (April 1996): 66. http://dx.doi.org/10.1016/0198-8859(96)85045-2.

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Shiina, Takashi. "Next generation sequencing based HLA genomic and polymorphism analyses." Major Histocompatibility Complex 22, no. 2 (2015): 84–94. http://dx.doi.org/10.12667/mhc.22.84.

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Dissertations / Theses on the topic "Genomic HLA"

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Aldener-Cannavá, Anna. "HLA polymorphism : genomic typing and impact on unrelated stem cell transplantation /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4593-4/.

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Mandage, Rajendra 1984. "Understanding interactions between EBV and human genomic variation." Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/586328.

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The EBV has been linked to multiple human disease phenotypes and has been associated with cancers and other infections. Recently single gene analysis and genome-wide analysis studies have been exploited to uncover the human genetic variants that are linked with EBV diseases. It also suggested the substantial role of individual host genetics and also provided a clue in understanding the interaction between virus and human. Furthermore, the outcome of the EBV infection is a complex phenomenon governs by the variation in the genetic architecture of the viral and human genomes and/or the interacting environmental factors. Therefore, this PhD work is mainly a large-scale effort towards the understanding of the human and EBV genetic architecture to uncover the role of genetic variation in EBV associated infections, disease susceptibility, immune recognition and invasion. Our results also provide a framework on the impact of human and EBV genetic variation and their unusual interactions that highlight the human genetic influence affecting viral load reflecting the clinical behavior of EBV in LCLs and the other side viral antigenic variation modulating immune response to sustain persistence infection. This EBV-human perturbation is essential to follow-up in the context of the susceptibility of individual populations to a specific EBV associated pathology.
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Pimentel-Santos, Fernando Manuel. "Ankylosing spondylitis: genomic and functional characterization of candidate genes and their repercussion in clinical practice." Doctoral thesis, Faculdade de Ciências Médicas. Universidade Nova de Lisboa, 2012. http://hdl.handle.net/10362/7806.

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RESUMO: Introdução: A espondilite anquilosante (EA) é uma doença inflamatória crónica caracterizada pela inflamação das articulações sacroilíacas e da coluna. A anquilose progressiva motiva uma deterioração gradual da função física e da qualidade de vida. O diagnóstico e o tratamento precoces podem contribuir para um melhor prognóstico. Neste contexto, a identificação de biomarcadores, assume-se como sendo muito útil para a prática clínica e representa hoje um grande desafio para a comunidade científica. Objetivos: Este estudo teve como objetivos: 1 - caracterizar a EA em Portugal; 2 - investigar possíveis associações entre genes, MHC e não-MHC, com a suscetibilidade e as características fenotípicas da EA; 3 - identificar genes candidatos associados a EA através da tecnologia de microarray. Material e Métodos: Foram recrutados doentes com EA, de acordo com os critérios modificados de Nova Iorque, nas consultas de Reumatologia dos diferentes hospitais participantes. Colecionaram-se dados demográficos, clínicos e radiológicos e colhidas amostras de sangue periférico. Selecionaram-se de forma aleatória, doentes HLA-B27 positivos, os quais foram tipados em termos de HLA classe I e II por PCR-rSSOP. Os haplótipos HLA estendidos foram estimados pelo algoritmo Expectation Maximization com recurso ao software Arlequin v3.11. As variantes alélicas dos genes IL23R, ERAP1 e ANKH foram estudadas através de ensaios de discriminação alélica TaqMan. A análise de associação foi realizada utilizando testes da Cochrane-Armitage e de regressão linear, tal como implementado pelo PLINK, para variáveis qualitativas e quantitativas, respetivamente. O estudo de expressão génica foi realizado por Illumina HT-12 Whole-Genome Expression BeadChips. Os genes candidatos foram validados usando qPCR-based TaqMan Low Density Arrays (TLDAs). Resultados: Foram incluídos 369 doentes (62,3% do sexo masculino, com idade média de 45,4 ± 13,2 anos, duração média da doença de 11,4 ± 10,5 anos). No momento da avaliação, 49,9% tinham doença axial, 2,4% periférica, 40,9% mista e 7,1% entesopática. A uveíte anterior aguda (33,6%) foi a manifestação extra-articular mais comum. Foram positivos para o HLA-B27, 80,3% dos doentes. Os haplótipo A*02/B*27/Cw*02/DRB1*01/DQB1*05 parece conferir suscetibilidade para a EA, e o A*02/B*27/Cw*01/DRB1*08/DQB1*04 parece conferir proteção em termos de atividade, repercussão funcional e radiológica da doença. Três variantes (2 para IL23R e 1 para ERAP1) mostraram significativa associação com a doença, confirmando a associação destes genes com a EA na população Portuguesa. O mesmo não se verificou com as variantes estudadas do ANKH. Não se verificou associação entre as variantes génicas não-MHC e as manifestações clínicas da EA. Foi identificado um perfil de expressão génica para a EA, tendo sido validados catorze genes - alguns têm um papel bem documentado em termos de inflamação, outros no metabolismo da cartilagem e do osso. Conclusões: Foi estabelecido um perfil demográfico e clínico dos doentes com EA em Portugal. A identificação de variantes génicas e de um perfil de expressão contribuem para uma melhor compreensão da sua fisiopatologia e podem ser úteis para estabelecer modelos com relevância em termos de diagnóstico, prognóstico e orientação terapêutica dos doentes. -----------ABSTRACT: Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disorder characterized by inflammation in the spine and sacroiliac joints leading to progressive joint ankylosis and in progressive deterioration of physical function and quality of life. An early diagnosis and early therapy may contribute to a better prognosis. The identification of biomarkers would be helpful and represents a great challenge for the scientific community. Objectives: The present study had the following aims: 1- to characterize the pattern of AS in Portuguese patients; 2- to investigate MHC and non-MHC gene associations with susceptibility and phenotypic features of AS and; 3- to identify candidate genes associated with AS by means of whole-genome microarray. Material and Methods: AS was defined in accordance to the modified New York criteria and AS cases were recruited from hospital outcares patient clinics. Demographic and clinical data were recorded and blood samples collected. A random group of HLA-B27 positive patients and controls were selected and typed for HLA class I and II by PCR-rSSOP. The extended HLA haplotypes were estimated by Expectation Maximization Algorithm using Arlequin v3.11 software. Genotyping of IL23R, ERAP1 and ANKH allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests as implemented in PLINK, for dichotomous and quantitative variables, respectively. Gene expression profile was carried out using Illumina HT-12 Whole-Genome Expression BeadChips and candidate genes were validated using qPCR-based TaqMan Low Density Arrays (TLDAs). Results: A total of 369 patients (62.3% male; mean age 45.4±13.2 years; mean disease duration 11.4±10.5 years), were included. Regarding clinical disease pattern, at the time of assessment, 49.9% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopathic disease. Acute anterior uveitis (33.6%) was the most common extra-articular manifestation. 80.3% of AS patients were HLA-B27 positive. The haplotype A*02/B*27/Cw*02/DRB1*01/DQB1*05 seems to confer susceptibility to AS, whereas A*02/B*27/Cw*01/DRB1*08/DQB1*04 seems to provide protection in terms of disease activity, functional and radiological repercussion. Three markers (two for IL23R and one for ERAP1) showed significant single-locus disease associations. Association of these genes with AS in the Portuguese population was confirmed, whereas ANKH markers studied did not show an association with AS. No association was seen between non-MHC genes and clinical manifestations of AS. A gene expression signature for AS was established; among the fourteen validated genes, a number of them have a well-documented inflammatory role or in modulation of cartilage and bone metabolism. Conclusions: A demographic and clinical profile of patients with AS in Portugal was established. Identification of genetic variants of target genes as well as gene expression signatures could provide a better understanding of AS pathophysiology and could be useful to establish models with relevance in terms of susceptibility, prognosis, and potential therapeutic guidance.
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Mendes, Fábio Henrique Kuriki. "Seleção natural em genes HLA e seu efeito sobre regiões adjacentes do genoma." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/41/41131/tde-02082013-161104/.

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O MHC é uma região genômica que contém genes de papel central na resposta imune adaptativa. Genes do MHC e, particularmente, genes HLA em humanos, estão envolvidos susceptibilidade e resistência a doenças infecciosas, na predisposição a doenças autoimunes e na rejeição de órgãos transplantados. Essas descobertas incentivaram uma série de estudos sobre padrões da variabilidade genética em genes HLA, que demonstraram possuir uma variação bastante distinta da expectativa neutra. Essa contundente evidência de seleção natural, ímpar no genoma humano, levanta uma série de perguntas a respeito das forças evolutivas específicas que agem nesses genes e as implicações genômicas para a evolução da região como um todo. O presente estudo investiga como a seleção natural afeta e é afetada pela diversidade de genes que estão ligados fisicamente a outros que constituem alvos de seleção. Nossa expectativa é que seleção balanceadora forte sobre genes HLA interfere na eficácia com que a seleção purificadora remove variantes deletérias em loci próximos. Especificamente, a partir da anotação funcional de variantes genéticas, testamos se grupos de genes ligados fisicamente aos genes HLA apresentam uma diversidade mais alta do que seria esperado na ausência de seleção balanceadora e de carona genética causada por ela, e se essa diversidade é enriquecida com variantes possivelmente deletérias. Por meio da análise de razão entre polimorfismos não-sinônimos e sinônimos (e diversas outras estatísticas relacionadas), fomos capazes de observar que loci próximos a genes HLA acumulam um excesso de variação não-sinônima (e portanto potencialmente deletéria). O grau de deleteriedade foi confirmado pelo emprego do software Polyphen 2, que utiliza como critério de classificação a conservação das sequências nucleotídicas e informação das estruturas protéicas, e pela análise de estatísticas como Pdel/Pn e Pdel/Ps. De acordo com testes de McDonald-Kreitman e o Índice de Neutralidade, entretanto, parte dessa variação deletéria se fixa em longo prazo, o que sugere que a seleção em genes HLA pode interferir tanto nos padrões de polimorfismos como de divergência
The MHC is a genomic region that contains genes with a central role in the adaptive immune response. Genes in the MHC region, in particular the HLA genes of humans, are involved in the differential susceptibility and resistance to infectious diseases, predisposition to autoimmune diseases and the rejection of transplanted organs. These findings have fueled a series of studies on patterns of genetic variation at HLA genes, which have conclusively demonstrated that their variation deviates from neutral expectations. Such strong evidence of natural selection, with few counterparts in the remainder of the human genome, raise a series of questions concerning the specific evolutionary forces acting on this region and their genomic implications for the evolution of the region as a whole. This work investigates how natural selection affects and is affected by the diversity of genes that are physically linked to those that are units of selection. Our expectation is that strong selection on HLA genes may interfere with the efficacy of selection in removing deleterious variants at closely linked loci. Specifically, by using functional annotations of genetic variants, we test whether sets of genes physically linked to the strongly selected HLA loci show a higher diversity than would be expected in the absence of balancing selection and genetic hitchhiking caused by it, and if this diversity is enriched for putatively deleterious variants. By analyzing the ratio of nonsynonymous to synonymous polymorphisms (and several related statistics) we were able to show that loci close to HLA genes are harboring an excess of nonsynonymous (and hence potentially deleterious) variation. The deleteriousness was confirmed by employing Polyphen 2 - a software that uses nucleotide sequence conservation and protein structure information to classify variants as deleterious or not - and computing statistics such as Pdel/Pn and Pdel/Ps. According to McDonald-Kreitman tests and the Neutrality Index, however, part of this putatively deleterious variation reaches fixation over long timespans, suggesting that selection at the HLA genes may be interfering with both the transient patterns of polymorphism and substitution processes
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Landry, Jonathan [Verfasser], and Stefan [Akademischer Betreuer] Wölfl. "The genomic and transcriptomic landscape of HeLa cells / Jonathan Landry. Betreuer: Stefan Wölfl." Heidelberg : Universitätsbibliothek Heidelberg, 2012. http://d-nb.info/1061054462/34.

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Xu, Huaigeng. "Targeted Disruption of HLA genes via CRISPR-Cas9 generates iPSCs with Enhanced Immune Compatibility." Kyoto University, 2019. http://hdl.handle.net/2433/242420.

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Ohadi, Mina. "Genome mapping of a locus for familial haemophagocytic lymphohistiocytosis." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314048.

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Bianchi, I. "LE BASI GENETICHE DELLA CIRROSI BILIARE PRIMITIVA: DAGLI STUDI DI ASSOCIAZIONE SU SINGOLO GENE AGLI STUDI SULL'INTERO GENOMA." Doctoral thesis, Università degli Studi di Milano, 2011. http://hdl.handle.net/2434/151770.

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Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology. Genetic factors are critical in determining susceptibility to PBC, but there has not been a clear association with specific genes. A multicenter case-control study was performed and HLA class II DRB1 associations were analyzed using a large cohort of 664 cases of PBC and 1,992 controls of Italian ancestry; healthy controls were rigorously matched by age, sex, and also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). After correction for multiple testing, DRB1*08 [odds ratio (OR) 3.35] and DRB1*02 (OR 0.9) were significantly associated with PBC, whereas alleles DRB1*11 (OR 0.4) and DRB1*13 (OR 0.7) were protective. When subjects were stratified according to their grandparental geographical origin, only the associations with DRB1*08 and DRB1*11 were common to all three areas. No significant associations were detected between specific DRB1 alleles and relevant clinical features represented by the presence of cirrhosis or serum autoantibodies. To further define the genetic factors conferring risk for PBC a genome-wide association screen for PBC was performed in an Italian cohort of 453 patients and 945 controls. In particular, 610,000 and 1 milion common variants were evaluated in PBC cases and controls, respectively. The results confirmed also by genome-wide approach a significant association at the HLA region. In addition a combined meta-analysis using a Canadian dataset showed a strong IL12A and IL12RB associations and identified newly associated loci at SPIB (OR 1.46), IRF5-TNPO3 (OR 1.63) and 17q12-21 (OR 1.38)
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Fries, Jonna. "Hela Jaget : en analys av Anna Rydstedts Genom nålsögat." Thesis, Växjö University, School of Humanities, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:vxu:diva-1061.

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Gregoracci, Gustavo Bueno. "Terapia experimental com bacteriófagos." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317028.

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Orientador: Marcelo Brocchi
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-19T03:47:25Z (GMT). No. of bitstreams: 1 Gregoracci_GustavoBueno_D.pdf: 6197096 bytes, checksum: 05eb5e18d8084e5c5f742c6ec5afd63d (MD5) Previous issue date: 2010
Resumo: Bacteriófagos são vírus que infectam bactérias e arqueias, representando as entidades biológicas mais abundantes do mundo e influenciando de maneira marcante populações naturais de seus hospedeiros. A terapia com bacteriófagos, que representa uma das primeiras formas modernas de combate a infecções bacterianas, foi recentemente redescoberta e vem sendo reavaliada seguindo metodologias atuais quanto à sua viabilidade terapêutica. Para completar a caracterização dos fagos de nossa coleção, sequenciamos completamente o genoma da maior parte destes, através da metodologia multiplex pair-ended utilizando a plataforma Illumina. Visando contribuir para verificação da viabilidade terapêutica de bacteriófagos testamos os efeitos protetor e terapêutico dos fagos Shfl1, Saen1v2 e Saen1v4, pertencentes à coleção de nosso laboratório, em modelos biológicos relevantes. O fago Shfl1, lítico contra Shigella flexneri, foi testado em ensaio de invasão em células HeLa. A redução de bactérias intracelulares foi mensurada independentemente através de plaqueamento e citometria de fluxo, além da observação direta por microscopia de fluorescência. O fago Saen1v2, lítico contra Salmonella Typhimurium, foi estudado quanto à biodistribuição e meia-vida em modelo murino, e uma variante viral com maior persistência in vivo foi selecionada. Essa variante, denominada Saen1v2p5, e o fago Saen1v4, lítico contra Salmonella Typhi, foram testados em modelo murino de infecção tifoide, contra seus respectivos hospedeiros. Encontramos similaridade genômica a fagos conhecidos, como T4, T7, T1 entre outros, em maior ou menor grau. Obtivemos um efeito protetor e terapêutico contra Shigella flexneri utilizando o fago Shfl1 em ensaio de invasão em cultura de células HeLa, verificado por todas as metodologias empregadas. Não verificamos efeito antimicrobiano in vivo do fago Saen1v2p5 em modelo murino de infecção por Salmonella Typhimurium. Por outro lado, observamos efeito terapêutico e protetor dose dependente utilizando o fago Saen1v4 em modelo murino de infecção por Salmonella Typhi. O sucesso obtido com baixas multiplicidades de infecção sugere um possível efeito indireto ou estimulação imune inespecífica
Abstract: Bacteriophages are viruses that infect Bacteria and Achaea, representing the most abundant biological entities in the world and markedly influencing natural host populations. Phage therapy, which represents one of the first modern ways to fight bacterial infections, was recently rediscovered and is being re-evaluated according to current methodologies regarding its therapeutic viability. In order to complete phage characterization in our collection, we sequenced completely the genomes of most of these, through the multiplex pair-ended methodology using the Illumina platform. Aiming to contribute to the therapeutic viability verification of bacteriophages we tested phage protective and therapeutic effects of Shfl1, Saen1v2 and Saen1v4, which belong to our collection, in biologically relevant models. Phage Shfl1, lytic against Shigella flexneri, was tested in a HeLa invasion assay. Intracellular bacteria reduction was measured independently through plating and flow cytometry, besides direct observation through fluorescent microscopy. Phage Saen1v2, lytic against Salmonella Typhimurium, was studied about its bio-distribution and half-life in murine model, and a viral variant with longer in vivo persistence was selected. This variant, denominated Saen1v2p5, and phage Saen1v4, lytic against Salmonella Typhi, were tested in murine typhoid model, against their respective hosts. Genomic similarity to known phages such as T4, T7, T1 among others, was found, in various degrees. We obtained both protective and therapeutic effect against Shigella flexneri using phage Shfl1 in the HeLa invasion assay, through all methodologies utilized. We could not verify in vivo antimicrobial effect of phage Saen1v2p5 in the murine model of Salmonella Typhimurium infection. On the other hand, we observed both therapeutic and protective dose dependent effect using phage Saen1v4 in Salmonella Typhi murine infection model. The success obtained with low multiplicities of infection may suggest a possible indirect effect or unspecific immune stimulation
Doutorado
Microbiologia
Doutor em Genetica e Biologia Molecular
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Books on the topic "Genomic HLA"

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Carrier, Carmelita Martins. Genomic variation of HLA-class II genes in multiplex juvenile type I diabetes. 1988.

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Schulkin, Jay. Conservation of CRF in Brains and its Regulation by Adrenal Steroids. Oxford University Press, 2017. http://dx.doi.org/10.1093/acprof:oso/9780198793694.003.0003.

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The regulation of the HPA axis has been categorized as the classical mechanism of slow-acting genomic regulation of gene products, but this has given way to both slow and fast regulation of the HPA axis. We do not know how cortisol restrains the production of CRF in the paraventricular nucleus, thereby directly decreasing ACTH and, subsequently, cortisol; we know the classical negative-feedback regulatory system, which provides a mechanism, but how it works, well, that is another thing. Glucocorticoids restrain the HPA axis, but not other regions of the brain, such as the central nucleus of the amygdala and bed nucleus of the amygdala. But we now know that both chemically and electrically, these regions are not the same (equal).
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Siebert, Stefan, Sengupta Raj, and Alexander Tsoukas. The genetics of axial spondyloarthritis. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198755296.003.0004.

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Family and twin studies have long suggested a large genetic component in ankylosing spondylitis (AS). The genetic association with HLA-B27 remains one of the strongest single gene variant associations reported in any complex polygenic disease. The exact mechanism by which HLA-B27 contributes to AS remains unknown, with three main theories proposed: the arthritogenic peptide, endoplasmic reticulum stress with unfolded protein response, and homodimerization theories. Genome-wide association studies have identified a number of other important susceptibility genes for AS, several of which overlap with other spondyloarthritis conditions. Of these, ERAP1 and IL-23R, are covered in more detail, highlighting their functional importance.
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Brown, Matthew A., and John Reveille. Genetics of spondyloarthritis. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198734444.003.0005.

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In addition to sharing clinical, histopathological, and immunological features, spondyloarthritis (SpA) encompasses a group of diseases that are genetically linked through shared associations with HLA-B27, as well as other genes of the IL-23R and aminopeptidase groups. Great progress has been made since the development of the genome-wide association study approach, with better dissection of the HLA associations of this group of diseases, as well as the discovery of multiple genetic loci found outside of the major histocompatibility complex, in ankylosing spondylitis (AS) in particular. These genetic data shed light on the related pathogenesis of AS and psoriatic arthritis (PsA), inflammatory bowel disease (IBD)-related arthritis, and reactive arthritis (ReA). Genetic associations also strengthen the suggestive data that Behçet’s disease (BD) and Familial Mediterranean Fever (FMF) are related to the more classical forms of SpA.
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Siebert, Stefan, Sengupta Raj, and Alexander Tsoukas. A brief history of ankylosing spondylitis. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198755296.003.0002.

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The history of ankylosing spondylitis (AS) dates back to the discovery of skeletons with characteristic spinal changes. The disease was further defined by correlating pathological and clinical features, and the development of clinical radiology. Subsequent epidemiology and familial studies highlighted the association with other related conditions as part of the spondyloarthritides. The discovery of HLA-B27 confirmed this association. Over the past two decades, genome-wide association studies, and advances in imaging and immunology have yielded dramatic insights into the disease and the development of highly effective therapies.
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Hinks, Anne, and Wendy Thomson. Genetics of juvenile rheumatic diseases. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199642489.003.0043_update_002.

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Juvenile rheumatic diseases are heterogeneous, complex genetic diseases; to date only juvenile idiopathic arthritis (JIA) has been extensively studied in terms of identifying genetic risk factors. The MHC region is a well-established risk factor but in the last few years candidate gene and large-scale genome-wide association studies have been utilized in the search for non-HLA risk factors. There are now 17 JIA susceptibility loci which reach the genome-wide significance threshold for association and a further 7 regions with evidence for association in more than one study. In addition, some subtype-specific associations are emerging. These risk loci now need to be investigated further using fine-mapping strategies and then appropriate functional studies to show how the variant alters the gene function. This knowledge will not only lead to a better understanding of disease pathogenesis for juvenile rheumatic diseases but may also aid in the classification of these heterogeneous diseases. It may identify new pathways for potential therapeutic targets and help in the prediction of disease outcome and response to treatment.
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Hinks, Anne, and Wendy Thomson. Genetics of juvenile rheumatic diseases. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199642489.003.0043_update_003.

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Juvenile rheumatic diseases are heterogeneous, complex genetic diseases; to date only juvenile idiopathic arthritis (JIA) has been extensively studied in terms of identifying genetic risk factors. The MHC region is a well-established risk factor but in the last few years candidate gene and large-scale genome-wide association studies have been utilized in the search for non-HLA risk factors. There are now 17 JIA susceptibility loci which reach the genome-wide significance threshold for association and a further 7 regions with evidence for association in more than one study. In addition, some subtype-specific associations are emerging. These risk loci now need to be investigated further using fine-mapping strategies and then appropriate functional studies to show how the variant alters the gene function. This knowledge will not only lead to a better understanding of disease pathogenesis for juvenile rheumatic diseases but may also aid in the classification of these heterogeneous diseases. It may identify new pathways for potential therapeutic targets and help in the prediction of disease outcome and response to treatment.
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Patisaul, Heather B., and Scott M. Belcher. Receptor and Enzyme Mechanisms as Targets for Endocrine Disruptors. Oxford University Press, 2017. http://dx.doi.org/10.1093/acprof:oso/9780199935734.003.0005.

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In this chapter, the current understanding of the mechanisms of endocrine disruption on the brain and nervous system are presented. Because the overwhelming majority of mechanistic studies on EDCs have focused on the actions mediated by nuclear hormone receptors, this mechanisms is described in detail. The chapter also discusses the classic transcriptional mechanisms of steroid action and the impact of EDCs on rapid signaling (non-genomic) mechanisms. It presents an overview of the enzymes and pathways involved in the biosynthesis of steroid hormones, which are critical to proper functioning of the HPA and HPG axis, and the neuroactive steroids synthesized and active in the mammalian brain. The potential for EDCs to alter metabolic enzymes, with a focus on possible targets in the metabolic blood-brain barrier, is presented as a potential, though largely unexplored, mode of EDC action in the brain.
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Walsh, Bruce, and Michael Lynch. Using Molecular Data to Detect Selection: Signatures from Multiple Historical Events. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198830870.003.0010.

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This chapter examines the search for a pattern of repetitive adaptive substitutions over evolutionary time. In contrast with the previous chapter, only a modest number of tests toward this aim have been proposed. The HKA and McDonald-Kreitman tests contrast the polymorphism to divergence ratio between different genomic classes (such as different genes or silent versus replacement sites within the same gene). These approaches can detect an excess of substitutions, which allows one to estimate the fraction of adaptive sites. This chapter reviews the empirical data on estimates of this fraction and discusses some of the sources of bias it its estimation. Over an even longer time scale, one can contrast the rate of change of sites in a sequence over a phylogeny. These tests require a rather special type of selection, wherein the same specific site (usually a codon) experiences multiple adaptive substitutions over a phylogeny, such as might occur in arms-race genes.
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Nordiska ministerrådets policy för integrering av hållbar utveckling, jämställdhet och ett barnrätts- och ungdomsperspektiv. Nordic Council of Ministers, 2020. http://dx.doi.org/10.6027/politiknord2020-717.

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Hållbar utveckling, jämställdhet och ett barnrätts- och ungdomsperspektiv är övergripande områden som är viktiga för hela Nordiska ministerrådets arbete. Ansvaret att ta hänsyn till dessa i Nordiska ministerrådets arbete gäller alla som verkar inom eller på uppdrag av Nordiska ministerrådet oavsett politikområde. Genom att stärka detta arbete säkerställer vi att Nordiska ministerrådets arbete är hållbart, jämställt, inkluderande, representativt och tillgängligt.
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Book chapters on the topic "Genomic HLA"

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Dawkins, R. L., P. H. Kay, E. Martin, and F. T. Christiansen. "The Genomic Structure of Ancestral Haplotypes Revealed by Pulsed Field Gel Electrophoresis (PFGE)." In Immunobiology of HLA, 893–95. New York, NY: Springer New York, 1989. http://dx.doi.org/10.1007/978-1-4612-3552-1_261.

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Monos, Dimitri S., Massimo Trucco, Richard S. Spielman, Susan F. Radka, Chester M. Zmijewski, and Malek Kamoun. "Biochemical and Genomic Characterization of HLA-DQ Gene Products Associated with DR3, DR4, and DR5 Haplotypes." In Immunobiology of HLA, 296–97. Berlin, Heidelberg: Springer Berlin Heidelberg, 1989. http://dx.doi.org/10.1007/978-3-662-39946-0_107.

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Kawaguchi, Shuji, and Fumihiko Matsuda. "High-Definition Genomic Analysis of HLA Genes Via Comprehensive HLA Allele Genotyping." In Methods in Molecular Biology, 31–38. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0389-5_3.

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Pötsch, L., L. Penzes, M. Prager-Eberle, P. M. Schneider, and Ch Rittner. "Sex Determination by Genomic Dot Blot Hybridization and HLA DQα Typing by PCR from Fixed Tissues." In Advances in Forensic Haemogenetics, 96–98. Berlin, Heidelberg: Springer Berlin Heidelberg, 1992. http://dx.doi.org/10.1007/978-3-642-77324-2_27.

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Jinam, Timothy A. "Human Leukocyte Antigen (HLA) Region in Human Population Studies." In Evolution of the Human Genome I, 173–79. Tokyo: Springer Japan, 2017. http://dx.doi.org/10.1007/978-4-431-56603-8_9.

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Bodmer, Julia. "World Distribution of HLA Alleles and Implications for Disease." In Ciba Foundation Symposium 197 - Variation in the Human Genome, 233–58. Chichester, UK: John Wiley & Sons, Ltd., 2007. http://dx.doi.org/10.1002/9780470514887.ch13.

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Paro, Renato, Ueli Grossniklaus, Raffaella Santoro, and Anton Wutz. "Biology of Chromatin." In Introduction to Epigenetics, 1–28. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-68670-3_1.

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AbstractThis chapter provides an introduction to chromatin. We will examine the organization of the genome into a nucleosomal structure. DNA is wrapped around a globular complex of 8 core histone proteins, two of each histone H2A, H2B, H3, and H4. This nucleosomal arrangement is the context in which information can be established along the sequence of the DNA for regulating different aspects of the chromosome, including transcription, DNA replication and repair processes, recombination, kinetochore function, and telomere function. Posttranslational modifications of histone proteins and modifications of DNA bases underlie chromatin-based epigenetic regulation. Enzymes that catalyze histone modifications are considered writers. Conceptually, erasers remove these modifications, and readers are proteins binding these modifications and can target specific functions. On a larger scale, the 3-dimensional (3D) organization of chromatin in the nucleus also contributes to gene regulation. Whereas chromosomes are condensed during mitosis and segregated during cell division, they occupy discrete volumes called chromosome territories during interphase. Looping or folding of DNA can bring regulatory elements including enhancers close to gene promoters. Recent techniques facilitate understanding of 3D contacts at high resolution. Lastly, chromatin is dynamic and changes in histone occupancy, histone modifications, and accessibility of DNA contribute to epigenetic regulation.
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Mehra, Narinder K., and Gurvinder Kaur. ". Genomic Diversity of HLA in the Indian Subcontinent." In Genomics and Health in the Developing World, 908–15. Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780195374759.003.0075.

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Toni Hò, Gia-Gia, Wiebke Hiemisch, Andreas Pich, Michelle Matern, Lareen Sophi Gräser, Rainer Blasczyk, Christina Bade-Doeding, and Gwendolin Sabrina Simper. "Small Molecule/HLA Complexes Alter the Cellular Proteomic Content." In New Insights into the Future of Pharmacoepidemiology and Drug Safety. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.97373.

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A medical product usually undergoes several clinical trials, including the testing of volunteers. Nevertheless, genomic variances in the patients cannot be considered comprehensively and adverse drug reactions (ADRs) are missed or misinterpreted during trials. Despite the relation between ADRs and human leukocyte antigen (HLA) molecules being known for several years, the fundamental molecular mechanisms leading to the development of such an ADR often remains only vaguely solved. The analysis of the peptidome can reveal changes in peptide presentation post-drug treatment and explain, for example, the severe cutaneous ADR in HLA-B*57:01-positive patients treated with the antiretroviral drug abacavir in anti-HIV therapy. However, as seen in the biophysical features of HLA-A*31:01-presented peptides, treatment with the anticonvulsant carbamazepine only induces minor changes. Since the binding of a drug to a certain HLA allelic variant is extremely distinct, the influence of the small molecule/protein complex on the proteomic content of a cell becomes clear. A sophisticated methodology elucidating the impact of drug treatment on cells is a full proteome analysis. The principal component analysis of abacavir, carbamazepine or carbamazepine-10,11-epoxid treated cells reveals clear clustering of the drug-treated and the untreated samples that express the respective HLA molecule. Following drug treatment, several proteins were shown to be significantly up- or downregulated. Proteomics and peptidomics are valuable tools to differential clinical outcomes of patients with the same HLA phenotype.
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Antoine, Dan, Neil French, and Munir Pirmohamed. "Predictive Strategies for ADRs – Biomarkers and In Vitro Models." In Pharmacology for Chemists: Drug Discovery in Context, 343–78. The Royal Society of Chemistry, 2017. http://dx.doi.org/10.1039/bk9781782621423-00343.

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It has been widely reported that currently used biomarkers of drug toxicity lack sensitivity, specificity and a fundamental mechanistic basis. The lack of qualified mechanistic biomarkers has resulted in a significant challenge to investigate the true extent and diagnosis of ADRs. Two current organ systems that are frequent toxicology targets for marketed drugs or those in development include the liver and kidney. The currently clinical available biochemical tests used for both of these organ systems lack sensitivity and specificity. There is also increasing interest in genomic biomarkers in drug safety, with most of the advances being seen with HLA gene polymorphisms and the risk for immune-mediated diseases affecting different organ systems, most prominently the skin and liver. We will focus on all these areas in this chapter.
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Conference papers on the topic "Genomic HLA"

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Zhao, Jian, Jie Hu, Xiuqin Zhang, Xuan Gao, Fan Tong, Xiaorui Fu, Yuting Yi, Yanfang Guan, Xuefeng Xia, and Jian'an Huang. "Abstract 1896: The genomic features of Chinese cancer patients harboring HLA LOH." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1896.

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Garcia-Marquez, MA, M. Thelen, E. Bauer, K. Wennhold, J. Lehmann, D. Keller, B. Gathof, et al. "10.02 Genomic HLA homozygosity is frequent in esophageal adenocarcinoma and related to low immunogenicity." In iTOC8 – the 8th Leading International Cancer Immunotherapy Conference in Europe, 8–9 October 2021, Virtual Conference. BMJ Publishing Group Ltd, 2021. http://dx.doi.org/10.1136/jitc-2021-itoc8.2.

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Beasley, Aaron, Anna Reid, Leslie Calapre, Michael Millward, Elin Gray, and Afaf Abed. "577 The variation of T-cell receptors (TCR) diversity and genomic human leukocyte antigen (HLA-I) among non-small cell lung cancer (NSCLC) patients expressing high PDL-1 (≥50%) versus those with low or no PDL1 (<50%)." In SITC 37th Annual Meeting (SITC 2022) Abstracts. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-sitc2022.0577.

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"Detection of the binding the stress HliA protein Synechocystis sp. with pigments." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Novosibirsk ICG SB RAS 2021, 2021. http://dx.doi.org/10.18699/plantgen2021-181.

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Malhotra, Raunaq, Alexandar Krasnitz, Anurag Sethi, Erik Lehnert, Elizabeth H. Williams, and Davis-Dusenbery N. Brandi. "Abstract 2348: Low-cost and accurate human leukocyte antigen (HLA) class I typing of The Cancer Genome Atlas on the Seven Bridges Cancer Genomics Cloud." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-2348.

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Harjanto, Dewi, Jennifer G. Abelin, Matthew Malloy, Prerna Suri, Tyler Colson, Scott P. Goulding, Amanda L. Creech, et al. "Abstract B23: Enhanced HLA-II epitope prediction for immunotherapy with novel proteomics and genomics approaches." In Abstracts: AACR Special Conference on Tumor Immunology and Immunotherapy; November 17-20, 2019; Boston, MA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/2326-6074.tumimm19-b23.

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"Alleles and haplotypes diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in Russia." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-212.

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"The effect of "early"protein of papillomavirus HPV16 E2 made in plant expression system on the base of tomato fruit on tumor formation in mice infected with cancer HeLa cells." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Novosibirsk ICG SB RAS 2021, 2021. http://dx.doi.org/10.18699/plantgen2021-168.

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Han, Chunchun, Wei Wang, Jiwen Wang, and Liang Li. "Classfication and Evolution of HLH Family Members in Poultry Genome." In 2009 WRI World Congress on Computer Science and Information Engineering. IEEE, 2009. http://dx.doi.org/10.1109/csie.2009.33.

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Carneiro, Luis Felipe Ferreira, Osmar Júnior Da Silva Silva, Matteus Gomes De Oliveira, and Salomão Bruno Dos Santos Brasil. "TERAPIA GÊNICA NO TRATAMENTO DE ANEMIA FALCIFORME, UMA REVISÃO DE LITERATURA." In II Congresso Brasileiro de Hematologia Clínico-laboratorial On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/hematoclil/133.

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Introdução: A anemia falciforme é causada por uma mutação pontual no gene beta da globina, essa substituição origina uma molécula de hemoglobina anormal denominada hemoglobina S (HbS), ao invés da hemoglobina normal chamada de hemoglobina A (HbA). Nesse sentido, com o recente desenvolvimento e aplicabilidade das técnicas de terapia gênica houve uma nova perspectiva de mais uma opção de cura, tendo como principal diferencial ser um tratamento de transplante de células hematopoiéticas (HSCs) autólogo. Objetivos: O objetivo dessa revisão é compilar as informações mais recentes sobre o uso da terapia gênica no tratamento de anemia falciforme. Métodos: Foi feito um levantamento de dados utilizando as bases de dados PubMed e Lilacs, sendo buscados os termos “sickle cell anemia”/”anemia falciforme” associados a “gene therapy”/”terapia gênica”. Resultados: A terapia gênica pode ser explicada como um tratamento certificado, constituído por um grupo de medicamentos ou por produtos de engenharia de tecidos e células processadas. Sendo utilizadas na aplicação da adição de um gene modificado e saudável na célula do paciente, através de transportadores recombinantes e não patogênicos, que adiciona um gene saudável para a restauração celular atribuindo uma nova função a célula alvo, e pode ser classificada como ex vivo e in vivo, em que cada uma é diferenciada pelo tipo de vetor que será responsável pelo carreamento do gene modificado até a célula alvo. Dentre as formas utilizadas na aplicação dessa técnica estão: adição de genes da globina e tecnologias de edição de genoma para diminuir os sintomas da doença falciforme; aumento da HbF ou corrigindo a sequência da β-globina, são delineadas manipulação da célula terapêutica no transplante de células-tronco autólogo, para ser alcançado a completa cura. Conclusão: O tratamento utilizando a terapia gênica ainda esbarra em muitas questões econômicas e socias apesar dos potenciais benefícios. Além disso, devido aos potenciais efeitos colaterais do uso de vírus como vetores em terapia gênica, é necessário mais progresso no desenvolvimento de novos vetores não virais. Os vetores virais atuais devem ser usados com cautela em humanos.
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Reports on the topic "Genomic HLA"

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Mevarech, Moshe, Jeremy Bruenn, and Yigal Koltin. Virus Encoded Toxin of the Corn Smut Ustilago Maydis - Isolation of Receptors and Mapping Functional Domains. United States Department of Agriculture, September 1995. http://dx.doi.org/10.32747/1995.7613022.bard.

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Ustilago maydis is a fungal pathogen of maize. Some strains of U. maydis encode secreted polypeptide toxins capable of killing other susceptible strains of U. maydis. Resistance to the toxins is conferred by recessive nuclear genes. The toxins are encoded by genomic segments of resident double-strande RNA viruses. The best characterized toxin, KP6, is composed of two polypeptides, a and b, which are not covalently linked. It is encoded by P6M2 dsRNA, which has been cloned, sequenced and expressed in a variety of systems. In this study we have shown that the toxin acts on the membranes of sensitive cells and that both polypeptides are required for toxin activity. The toxin has been shown to function by creating new pores in the cell membrane and disrupting ion fluxes. The experiments performed on artificial phospholipid bilayers indicated that KP6 forms large voltage-independent, cation-selective channels. Experiments leading to the resolution of structure-function relationship of the toxin by in vitro analysis have been initiated. During the course of this research the collaboration also yielded X-ray diffracion data of the crystallized a polypeptide. The effect of the toxin on the pathogen has been shown to be receptor-mediated. A potential receptor protein, identified in membrane fractions of sensitive cells, was subjected to tryptic hydrolysis followed by amino-acid analysis. The peptides obtained were used to isolate a cDNA fragment by reverse PCR, which showed 30% sequence homology to the human HLA protein. Analysis of other toxins secreted by U. maydis, KP1 and KP4, have demonstrated that, unlike KP6, they are composed of a single polypeptide. Finally, KP6 has been expressed in transgenic tobacco plants, indicating that accurate processing by Kex2p-like activity occurs in plants as well. Using tobacco as a model system, we determined that active antifungal toxins can be synthesized and targeted to the outside of transgenic plant cells. If this methodology can be applied to other agronomically crop species, then U. maydis toxins may provide a novel means for biological control of pathogenic fungi.
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Gur, Amit, Edward Buckler, Joseph Burger, Yaakov Tadmor, and Iftach Klapp. Characterization of genetic variation and yield heterosis in Cucumis melo. United States Department of Agriculture, January 2016. http://dx.doi.org/10.32747/2016.7600047.bard.

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Project objectives: 1) Characterization of variation for yield heterosis in melon using Half-Diallele (HDA) design. 2) Development and implementation of image-based yield phenotyping in melon. 3) Characterization of genetic, epigenetic and transcriptional variation across 25 founder lines and selected hybrids. The epigentic part of this objective was modified during the course of the project: instead of characterization of chromatin structure in a single melon line through genome-wide mapping of nucleosomes using MNase-seq approach, we took advantage of rapid advancements in single-molecule sequencing and shifted the focus to Nanoporelong-read sequencing of all 25 founder lines. This analysis provides invaluable information on genome-wide structural variation across our diversity 4) Integrated analyses and development of prediction models Agricultural heterosis relates to hybrids that outperform their inbred parents for yield. First generation (F1) hybrids are produced in many crop species and it is estimated that heterosis increases yield by 15-30% globally. Melon (Cucumismelo) is an economically important species of The Cucurbitaceae family and is among the most important fleshy fruits for fresh consumption Worldwide. The major goal of this project was to explore the patterns and magnitude of yield heterosis in melon and link it to whole genome sequence variation. A core subset of 25 diverse lines was selected from the Newe-Yaar melon diversity panel for whole-genome re-sequencing (WGS) and test-crosses, to produce structured half-diallele design of 300 F1 hybrids (MelHDA25). Yield variation was measured in replicated yield trials at the whole-plant and at the rootstock levels (through a common-scion grafted experiments), across the F1s and parental lines. As part of this project we also developed an algorithmic pipeline for detection and yield estimation of melons from aerial-images, towards future implementation of such high throughput, cost-effective method for remote yield evaluation in open-field melons. We found extensive, highly heritable root-derived yield variation across the diallele population that was characterized by prominent best-parent heterosis (BPH), where hybrids rootstocks outperformed their parents by 38% and 56 % under optimal irrigation and drought- stress, respectively. Through integration of the genotypic data (~4,000,000 SNPs) and yield analyses we show that root-derived hybrids yield is independent of parental genetic distance. However, we mapped novel root-derived yield QTLs through genome-wide association (GWA) analysis and a multi-QTLs model explained more than 45% of the hybrids yield variation, providing a potential route for marker-assisted hybrid rootstock breeding. Four selected hybrid rootstocks are further studied under multiple scion varieties and their validated positive effect on yield performance is now leading to ongoing evaluation of their commercial potential. On the genomic level, this project resulted in 3 layers of data: 1) whole-genome short-read Illumina sequencing (30X) of the 25 founder lines provided us with 25 genome alignments and high-density melon HapMap that is already shown to be an effective resource for QTL annotation and candidate gene analysis in melon. 2) fast advancements in long-read single-molecule sequencing allowed us to shift focus towards this technology and generate ~50X Nanoporesequencing of the 25 founders which in combination with the short-read data now enable de novo assembly of the 25 genomes that will soon lead to construction of the first melon pan-genome. 3) Transcriptomic (3' RNA-Seq) analysis of several selected hybrids and their parents provide preliminary information on differentially expressed genes that can be further used to explain the root-derived yield variation. Taken together, this project expanded our view on yield heterosis in melon with novel specific insights on root-derived yield heterosis. To our knowledge, thus far this is the largest systematic genetic analysis of rootstock effects on yield heterosis in cucurbits or any other crop plant, and our results are now translated into potential breeding applications. The genomic resources that were developed as part of this project are putting melon in the forefront of genomic research and will continue to be useful tool for the cucurbits community in years to come.
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Nilsson, Hans, Magnus Appelberg, and Thomas Axenros. Provtagningsmetoder av akvatiska resurser med 3R i fokus. Institutionen för akvatiska resurser, Sveriges lantbruksuniversitet, 2023. http://dx.doi.org/10.54612/a.5o01b216ml.

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Flertalet av de övervakningsmetoder av fisk- och skaldjur som idag används globalt är dödande eller invasiva. Under 2020 hanterade SLU Aqua över 9 miljoner individer av fisk under fiskerioberoende provtagning. I Sverige, till skillnad från övriga Europa, räknas även de fiskar som fångas i provfiske till försöksdjur och regeringen har anmodat att myndigheter som använder försöksdjur bör upprätta strategier för sitt arbete med frågor som rör 3R, dvs. Replace (ersätta), Reduce (minska) och Refine (förfina). I syfte att undersöka möjligheterna att implementera 3R i SLU Aquas övervakning av fiskbestånd, redovisas i denna rapport möjliga metoder för att: Ersätta – Genom fiskeriberoende provtagning i syfte att ta fram förvaltningsunderlag för bedömning av beståndsstatus för Vänerns gösbestånd och kartlägga effekter av fiske på gös i Vänern (Kapitel 5) Minska – Genom studier av hydroakustisk frekvensrespons hos fisk och/eller användandet av trålmonterad stereovideo se på möjligen att reducera behovet av trålning under hydroakustiska trålundersökningar (Kapitel 2 och 3). Genom att komplettera nätprovfiske med hydroakustik, elfiske och eDNA reducera mängden dödad fisk i denna undersökningstyp (Kapitel 4). Förfina – Genom att kombinera olika metoder öka mängden kunskap varje provtagen individ ger samt hela ekosystem (Kapitel 3 och 4).
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Haikola, Simon, and Jonas Anshelm. Staten, marknaden och industripolitikens återupprättelse: Visioner om transportsystemets klimatomställning, 2006-2022. Linköping University Electronic Press, April 2023. http://dx.doi.org/10.3384/9789180750790.

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Trots upprepade politiska utfästelser om att transportsystemet ska bli fossilfritt har dess omställning gått trögt. Det har länge funnits en påtaglig kontrast mellan visionerna för transportsystemets omställning och de faktiskt vidtagna åtgärderna. De dominerande förklaringarna till denna kontrast, liksom föreställningarna om vad som kan göras, har skiftat över tid och beroende på vilken regering som suttit vid makten. I grunden kretsar de emellertid alltid kring samma frågor: Hur väl rustat är det svenska planeringssystemet för att genomföra en fundamental omställning av transporterna? I vilken omfattning kräver transportsystemets omställning en mer djupgående förändring av samhället? Vilken roll bör stat och marknad ha i transportsystemets omställning? I denna bok skildrar vi hur den offentliga diskussionen om transportsystemet förändrats under de fyra olika regeringar som suttit vid makten mellan 2006-2022. Genom att följa formuleringen av politiska visioner i statliga utredningar och hur dessa visioner diskuterats i den offentliga debatten visar vi hur en period av utpräglat marknadsliberal politik utmanas av klimatkeynesianistiska idéer. Samtidigt har hela undersökningsperioden karakteriserats av betydande institutionella låsningar.
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Hellström, Lisa, and Linda Beckman. "Det är lite mer så här mainstream att ha psykisk ohälsa" : Samtal om ungas behov och livsfärdigheter. Malmö universitet, 2021. http://dx.doi.org/10.24834/isbn.9789178771691.

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Denna rapport ingår i forskningsprojektet Att skapa goda livsfärdigheter bland unga. Den första delrapporten var en nationell och internationell kartläggning över initiativ och insatser för att främja psykisk hälsa bland unga. Bland insatser som verkar mer lovande – och till synes har goda möjligheter att göra skillnad för ungas psykiska hälsa - framträder insatser vars syfte är att höja kunskapen om psykisk hälsa bland unga och vuxna. Ökad kunskap om psykisk hälsa har visat sig vara ett viktigt verktyg för att utveckla färdigheter i hur man tolkar och förstår sina egna känslor och sin kropp och när man behöver kontakta vården. Dessutom är dessa insat-ser ofta samhällsekonomiskt kostnadseffektiva, eftersom de ger unga bättre livsfärdigheter och på sikt leder till minskat vårdsökande och bättre förutsättningar att klara skolan och i förlängningen arbetslivet. Sådana satsningar går även i linje med Barnkonventionen 24§ om alla barns rätt till bästa möjliga hälsa, som sedan 2020 är lag i Sverige. Rekommendat-ioner från den första delrapporten innefattar att rusta unga med färdigheter för att möta livets svårigheter och höja kunskapen om psykisk ohälsa. Det handlar också om att bistå vuxna med kunskap om psykisk hälsa och verk-tyg som främjar hälsa för att kunna stödja unga. Insatser för att främja unga personers hälsa bör följas upp under en längre tid.I denna rapport presenteras röster från unga och yrkesverksamma vuxna i ungas närhet om ungas livssituation kopplat till livsfärdigheter, psykisk hälsa och behov av stöd. Genom att lyssna in unga kan vi bättre hitta framgångsfaktorer för att främja ungas psykiska hälsa och välbefinnande.
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Montefusco, Maria. Ett nordiskt samarbete för alla – Funktionshindersintegrering i Nordiska ministerrådets verksamhet 2021. Nordens välfärdscenter, 2021. http://dx.doi.org/10.52746/zdjo7646.

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Det nordiska samarbetet ska vara tillgängligt och inkluderande, och den politik som genereras ska vara relevant för alla nordbor oavsett funktionsförmåga. I den här rapporten presenteras hur arbetet går, och vad som händer område för område. Att integrera ett funktionshindersperspektiv handlar för Nordiska ministerrådet om att synlig- och tydliggöra situation och behov hos personer med funktionsnedsättning samt att främja inkludering genom universell utformning och tillgänglighet. Det kan gälla praktiska saker, så som att politiska möten ska vara tillgängliga och det ska gå att ta del av ministerrådets rapporter och hemsida även med digitala hjälpmedel. Det handlar också om att främja inkludering av personer med olika typer av funktionsnedsättning i den politik som utvecklas genom samarbetet. Målet är att alla relevanta politikområden, administration och institutioner inom det nordiska samarbetet ska ha ett integrerat funktionshindersperspektiv. I den här statusrapporten går vi igenom allt arbete som skett under 2021, område för område. De olika områdena blickar också framåt och ser vad nästa steg är för att blir ännu mer inkluderande och tillgängliga.
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Barash, Itamar, J. Mina Bissell, Alexander Faerman, and Moshe Shani. Modification of Milk Composition via Transgenesis: The Role of the Extracellular Matrix in Regulating Transgene Expression. United States Department of Agriculture, July 1995. http://dx.doi.org/10.32747/1995.7570558.bard.

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Altering milk composition via transgenesis depends on three main factors. (1) The availability of an efficient regulatory sequences for targeting transgene(s) to the mammary gland; (2) a reliable in vitro model to test the expression of transgenes prior to their introduction to the animal genome; and (3) better understanding of the major factors which determine the rate of gene expression and protein synthesis. The current studies provide the necessary means and knowledge to alter milk protein composition via transgenesis. The following specific goals were achieved: a: Identifying regulatory regions in the b-lactoglobulin (BLG) gene and the cross-talk between elements which enabled us to construct an efficient vector for the expression of desirable cDNA's in the mammary gland. b: The establishment of a sheep mammary cell line that serves as a model for the analysis of endogenous and exogenous milk protein synthesis in the mammary gland of livestock. c: An accurate comparison of the potency of the 5' regulatory sequences from the BLG and whey acidic protein (WAP) promoters in directing the expression of human serum albumin (HSA) to the mammary gland in vitro and in vivo. In this study we have also shown that sequences within the coding region may determine a specific pattern of expression for the transgene, distinct from that of the native milk protein genes. d: Characterizing the dominant role of ECM in transgene expression in mammary epithelial cells. e: Further characterization of the BCE-1 enhancer element in the promoter of the b-casein gene as a binding site for the c/EBP-b and Stat5. Identifying its interaction with chromatin and its up regulation by inhibitors of histone deacetylation. f: Identifying a mechanism of translational control as a mediator for the synergistic effect of insulin and prolactin on protein synthesis in the mammary gland.
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Bergström, Ulf, and Mårten Erlandsson. Spiggens påverkan på rekryteringsområden för abborre och gädda i Östersjön. Institutionen för akvatiska resurser, Sveriges lantbruksuniversitet, 2022. http://dx.doi.org/10.54612/a.4bb5blrfa9.

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Storspigg har visat sig ha en negativ påverkan på rekryteringen av rovfiskar längs Östersjökusten, framför allt gädda och abborre, genom predation på ägg och larver. Detta leder till minskade rovfiskbestånd i kustzonen och en förlust av viktiga ekosystemfunktioner. I den här studien har vi kvantifierat omfattningen av denna störning med hjälp av rumslig och statistisk modellering där vi undersöker hur utbredning och abundans av rovfiskens reproduktionsområden förändrats över tid. I analyserna nyttjar vi data från de omfattande undersökningar av kustfiskens reproduktion längs ostkusten som gjorts med hjälp av tryckvåg från slutet av 1970-talet och framåt. Vi har tillämpat tre olika analysmetoder för att skatta förändringen i reproduktionsområden, i syfte att få en uppfattning om spannet i uppskattningarna. Vi har nyttjat två modeller från redan publicerade vetenskapliga artiklar, och även utvecklat en ny modell. Den ena av de två publicerade modellerna beskriver utvecklingen i täthet abborre och spigg över tid (Eriksson m fl 2021), medan den andra beskriver utvecklingen av ytor med rovfiskdominans (Eklöf m fl 2020). Den nyutvecklade modellen beskriver i sin tur förändringar i ytan lämpliga reproduktionsområden för abborre och gädda. De olika analyserna har i någon mån varierande geografisk täckning, som mest omfattande kuststräckan från norra Skåne län till södra Gävleborgs län. Sammantaget visar analyserna på betydande nedgångar i reproduktionen av abborre och gädda längs centrala Östersjökusten de senaste 30-40 åren. Resultaten visar att ytan fungerande reproduktionsområden för abborre och gädda minskat med i storleksordningen 40-65%, medan tätheten abborryngel kan ha minskat med så mycket som 80 %. Det är framför allt tidigare mycket produktiva rekryteringsområden för abborre och gädda längs öppna kuststräckor och i mellan- och ytterskärgårdar som gått förlorade. De tydliga sambanden mellan spigg och rekrytering av abborre och gädda indikerar att spiggen har varit en starkt bidragande orsak till nedgången, och framför allt att spiggen sannolikt blockerar en återkomst av abborre och gädda till områden där reproduktionen slagits ut. Förlusten av lokala rovfiskbestånd i skärgårdarna har en negativ påverkan inte bara på fisket, utan minskar även kustekosystemets förmåga att motstå de negativa effekterna av övergödning. En angelägen fråga för kommande forskning är att förstå mekanismerna bakom den dramatiska spiggökningen, och att identifiera metoder för att stärka reproduktionen och återetablera bestånd av abborre och gädda i de störda områdena.
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Franzén, Fredrik, Emma Svahn, Anna Lingman, and Ingrid Bergman. Biologisk recipientkontroll vid Oskarshamns kärnkraftverk : årsrapport för 2022. Institutionen för akvatiska resurser, Sveriges lantbruksuniversitet, 2023. http://dx.doi.org/10.54612/a.4c0gq2dgmg.

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Oskarshamns kärnkraftverk (OKG AB) påverkar den omgivande havsmiljön, främst genom användning av kylvatten. Den kylvattenpåverkade recipientens vattentemperatur var i medeltal 3,4 °C varmare än referensområdet Borholmsfjärden under 2022. Under 2022 pågick inga särskilda studier av fiskförluster i kylvattenhanteringen och det rapporterades inga avvikande händelser från kraftverkets silstation. Revisionsavställningen under våren, innebar en utebliven värmeökning i Hamnefjärden, vilket sannolikt påverkade resultatet i vårfisket med biologiska länkar till att en större andel av arterna var så kallade kallvattenarter som har högre förekomst i vatten med lägre temperaturer. Även ryssjefisket bör ha påverkats av detta och det kan vara en del i förklaringen till de låga ålfångsterna. I ryssjorna slogs däremot nytt fångstrekord av svartmunnad smörbult i år igen och storspigg fångades i ovanligt stort antal. I fisket med biologiska länkar, nätlänkar och nordiska kustöversiktsnät var fångsterna stora av abborre, mört, björkna och andra karpfiskar. De skillnader vi såg i fiskfångsterna mellan områdena kan förklaras av naturliga skillnader i temperatur, exponeringsgrad och geografisk lokalisering snarare än påverkan av varmvattenutsläppen från kärnkraftverket. I vårens fiske med kustöversiktsnät utanför Hamnefjärdens mynning registrerades låga fångster av de flesta för fisket vanligen förekommande arterna. Störning från säl noterades i nära 90 procent av fiskeansträngningarna. De varma somrarna 2018 och 2021 har resulterat i att en stor andel av de fångade abborrarna i provfiskena var fyra respektive ett år gamla. Konditionsvärdet för abborr- och mörthonor låg i samtliga områden omkring Simpevarp och Kvädöfjärden på eller över gränsvärdet för god kondition. Vid 2022 års provtagningar påträffades inga abborrhonor med missbildade gonader i något av ovan nämnda områden. Majoriteten av fiskar med sjukdomssymptom fångades i Simpevarp. Endast en sjuk fisk noterades i Kvädöfjärden. Antalet årsyngel av abborre och mört var lågt i Hamnefjärden 2022. Fångsterna i yrkesfisket efter vandrande ål, så kallad blankål, var återigen ett av de lägsta sedan journalföringen av detta fiske startades 1972. Under 2022 års undersökning av fauna på mjuka bottnar registrerades totalt 19 arter i Simpevarp och 21 arter i referensområdet Kvädöfjärden. Östersjömusslan var den vanligast förekommande arten på grunda bottnar och på djupa bottnar i Kvädöfjärden. På Simpevarps djupa bottnar var den rörbyggande havsborstmasken Pygospio elegans den mest förekommande arten. Vitmärla, en art som används som indikator för bland annat förändringar i halter av näringsämnen, sjönk ytterligare i antal på Kvädöfjärdens stationer. I år hittades den inte alls på grunda bottnar i Simpevarp. På djupa bottnar i samma område har den inte registrerats sedan 2013.
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Neumann, Wiebke, Fredrik Stenbacka, Jonas Malmsten, Anders Johansson, and Göran Ericsson. Årsrapport GPS-märkta älgar och inventeringar i brandområdet 2021-2022 – Fördelning, rörelse, livsmiljö, bärris och spillning. Institutionen för vilt, fisk och miljö, Sveriges lantbruksuniversitet, 2022. http://dx.doi.org/10.54612/a.4bj3vproqo.

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Nu har det redan gått två år sen vi sjösatte referensområdet ’Ljusdal’. Vi ser att årets observationer förstärker bilden vad vi såg året innan i området, samt vissa observationer liknar vad vi ser i andra studieområden, medan andra skiljer sig åt. Studieområdet i Ljusdal är speciellt i två avseenden som berör älgar direkt och därmed skiljer sig åt från andra studieområden: brandfältet och en hög täthet av brunbjörn. Som förväntat ser vi skillnader mellan olika älgindivider och resultaten liknar vad vi sett i andra delar av landet - en del älgar har helt skilda sommar- och vinterområden, andra har områden som överlappar delvis, och ett fåtal verkar ha i stort sett helt överlappande områden. Av de 39 älgar vi kunde följa under mars 2021-2022, var drygt hälften stationära där några älgar har förflyttat sig bara en kort sträcka mellan sitt vinter- och sommarområde. Den andra halvan hade klart avskilda säsongsområden där merparten höll sig inom 20-25 km radie till sitt vinterområde. Men vi kunde också följa några riktiga långvandrare! Tjugofem av de 39 GPS-märkta älgarna kunde vi lokalisera i brandfältet under året. Hur länge älgarna uppehöll sig inom brandområdet varierade mellan individerna. Stationära älgkor återfanns fler dagar inom området jämfört med vandringskorna. Älgarna nyttjade brandfältet framförallt under vegetationsperioden (maj-okt/nov) där några rörde sig inom brandområdet medan många älgar främst rörde sig i ytterkanterna. Alla kor, förutom F1874, F1887 och F1924, kalvade och vid hälften av kalvningarna föddes tvillingkalvar. Medelkalvningsdagen var 18:e maj. Sommaröverlevnaden av de årskalvar som föddes under kalvningssäsongen 2021 var mellan 17 och 26% fram till jaktstarten och låg därmed högre än året innan då överlevnad låg mellan 13-17 %. Sommeröverlevnaden är betydligt lägre jämfört med områden utan större rovdjur. I studieområdet i Ljusdal utsätts årskalvar för predation framförallt av björn. För en tredjedel av kalvarna som försvann under sommaren kunde vi verifiera björnpredation genom fynd i fält och för ytterligare en tredje del misstänker vi predation. Vid vinterkoll efter jakten var överlevnaden 12%. Insamlingen av prover under jakten resulterade i ca 70 käkar och 20 kompletta reproduktionsorgan från hondjuren. Medelåldern hos de bedömda fällda hondjuren var 8.4 år och hos tjurar 4.4 år, och de respektive slaktvikterna låg på ca 188.0 och 201.0 kg. Slaktvikten för kalv låg i snitt på 71.5 kg. Fetthalten i benmärgen var i medel 81% för kor, 70% för tjurar och 74% för kalvar. En viktig orsak till att försökspopulationen i Ljusdal fungerar så bra är det nära samarbetet med alla intresserade. Intresset är mycket stort, många olika användare är inne på hemsidan www.slu.se/alg-forskning. Författarna ansvarar ensamma för innehållet i rapporten.
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