The involvement of anti-inflammatory protein, Annexin A1, in ocular toxoplasmosis

Purpose: The aim of this study was to evaluate the expression of the protein annexin A1 (ANXA1), a potent endogenous regulator of the inflammatory process, in ocular toxoplasmosis. Methods: C57BL/6 female mice were infected using intravitreal injections of either 10 6 tachyzoites of Toxoplasma gondii (RH strain; T. gondii) or PBS only (control groups). After 24, 48, and 72 h, animals were sacrificed and their eyes were harvested for histopathological, immunohistochemical, and ultrastructural immunocytochemical analysis of ANXA1. Human retinal pigment epithelial (RPE) cells (ARPE-19) were infected in vitro with T. gondii and collected after 60, 120, 240 min, and 24 h. Results: Compared with non-infected eyes, an intense inflammatory response was observed in the anterior (24 h after infection) and posterior segments (72 h after infection) of the infected eye, characterized by neutrophil infiltration and by the presence of tachyzoites and their consequent destruction along with disorganization of normal retina architecture and RPE vacuolization. T. gondii infection was associated with a significant increase of ANXA1 expression in the neutrophils at 24, 48, and 72 h, and in the RPE at 48 and 72 h. In vitro studies confirmed an upregulation of ANXA1 levels in RPE cells, after 60 and 120 min of infection with T. gondii. Conclusions: The positive modulation of endogenous ANXA1 in the inflammatory and RPE cells during T. gondii infection suggests that this protein may serve as a therapeutic target in ocular toxoplasmosis. © 2012 Molecular Vision

Xist-dependent imprinted X inactivation and the early developmental consequences of its failure

The long noncoding RNA Xist is expressed from only the paternal X chromosome in mouse preimplantation female embryos and mediates transcriptional silencing of that chromosome. In females, absence of Xist leads to postimplantation lethality. Here, through single-cell RNA sequencing of early preimplantation mouse embryos, we found that the initiation of imprinted X-chromosome inactivation absolutely requires Xist. Lack of paternal Xist leads to genome-wide transcriptional misregulation in the early blastocyst and to failure to activate the extraembryonic pathway that is essential for postimplantation development. We also demonstrate that the expression dynamics of X-linked genes depends on the strain and parent of origin as well as on the location along the X chromosome, particularly at the first 'entry' sites of Xist. This study demonstrates that dosage-compensation failure has an effect as early as the blastocyst stage and reveals genetic and epigenetic contributions to orchestrating transcriptional silencing of the X chromosome during early embryogenesis.This work was funded by a fellowship of Région Ile-de-France (DIM STEMP OLE) to M.B., the Paris Alliance of Cancer Research Institutes (PACRI-ANR) to LS and ERC Advanced Investigator award (ERC-2010-AdG–No.250367), EU FP7 grants SYBOSS (EU 7th Framework G.A. no. 242129) and MODHEP (EU 7th Framework G.A. no. 259743), La Ligue, Fondation de France, Labex DEEP (ANR-11-LBX-0044) part of the IDEX Idex PSL (ANR-10-IDEX-0001-02 PSL) and ABS4NGS (ANR-11-BINF-0001) to E.H and France Genomique National infrastructure (ANR-10-INBS09) to EH, NS, EB

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Novel imaging techniques and biological methods for breast cancer evaluation: overview and update

NTRODUZIONE: Il tumore al seno (breast cancer, BC) \ue8 una malattia eterogenea e complessa ed \ue8 il tumore pi\uf9 comune nelle donne nella maggior parte dei paesi. Poich\ue9 il rilevamento precoce del BC \ue8 vitale per garantire il massimo beneficio dal trattamento, evidenziamo recenti studi di ricerca che si occupano del rilevamento e della caratterizzazione del BC, concentrandosi sia su nuove tecniche di imaging medico che su test biologici. Esaminiamo brevemente il ruolo delle nuove modalit\ue0 di imaging emergenti e descriviamo il ruolo complementare dei metodi biologici per la rilevazione e la caratterizzazione del BC come biopsia liquida, microRNA, ctDNA, CTC e test genetici. ACQUISIZIONE DELL\u2019EVIDENZA: Abbiamo condotto una revisione della letteratura su PubMed/MEDLINE, concentrandoci su studi recenti (pubblicati dopo il 2014 fino a gennaio 2020) per descrivere nuovi metodi di rilevamento per il BC, coprendo le modalit\ue0 radiologiche e biologiche emergenti. Sono stati inclusi articoli in lingua inglese. SINTESI DELL\u2019EVIDENZA: Attraverso questa revisione, sosteniamo l\u2019idea che un approccio sinergico che integri le caratteristiche morfologiche e biologiche di BC sar\ue0 probabilmente il futuro nella diagnosi e caratterizzazione precoce del BC. CONCLUSIONI: I radiologi dovrebbero essere informati del potenziale di nuovi metodi per la rilevazione della BC non strettamente basati sull\u2019imaging medico.INTRODUCTION: Breast cancer (BC) is a heterogeneous and complex disease and it is the most common cancer in women in most countries. Since early-stage detection of BC is vital for ensuring the most benefit from treatment, we highlight recent research studies dealing with BC detection and characterization, focusing both on new medical imaging techniques and biological tests. We briefly review the role of new emerging imaging modalities and describe the complementary role of biological methods for BC detection and charaterization such as liquid biopsy, microRNAs, ctDNA, CTCs, and genetic tests. EVIDENCE ACQUISITION: We conducted a literature review on PubMed/MEDLINE, focusing on recent studies (published after January 2020) to describe new detection methods for BC, covering emerging radiological and biological modalities. Articles in English language were included. EVIDENCE SYNTHESIS: Through this review, we support the idea that a synergistic approach integrating the morphological and biological features of BC will probably be the future in the early detection and characterization of BC. CONCLUSIONS: Radiologists should be kept informed of the potential of new methods for BC detection not strictly based on medical imaging

The concurrent occurrence of Leishmania chagasi infection and childhood acute leukemia in Brazil

AbstractObjectiveThis study investigated the co-existence of Leishmania chagasi infection and childhood leukemia in patients naïve to treatment; this has serious clinical and epidemiological implications.MethodsThe seroprevalence of L. chagasi antibodies prior to any treatment was investigated in children with clinical features of acute leukemia. Serological tests were performed in 470 samples drawn from under 14-year-old children from different regions of Brazil with clinical suspicion of acute leukemia. Acute leukemia subtypes were characterized by immunophenotyping using flow cytometry. Morphological analyses of bone marrow aspirates were systematically performed to visualize blast cells and/or the formation of L. chagasi amastigotes. Data analysis used a standard univariate procedure and the Pearson's chi-square test.ResultsThe plasma of 437 children (93%) displayed antibodies against L. chagasi by indirect immunofluorescence assay and enzyme-linked immunosorbent assay tests. Of the 437 patients diagnosed from 2002 to 2006, 254 had acute lymphoblastic leukemia, 92 had acute myeloid leukemia, and 91 did not have acute leukemia. The seroprevalence of L. chagasi antibodies according to the indirect immunofluorescence assay test (22.5%) was similar in children with or without acute leukemia (p-value=0.76). The co-existence of visceral leishmanasis and acute leukemia was confirmed in 24 children. The overall survival of these children was poor with a high death rate during the first year of leukemia treatment.ConclusionIn the differential diagnosis of childhood leukemia, visceral leishmanasis should be considered as a potential concurrent disease in regions where L. chagasi is endemic

Seroprevalence, clinical and biochemical data of dogs naturally infected by Leishmania and phlebotominae sandfly fauna in an endemic area in São Luis Island, Maranhão State, Brazil

Submitted by Sandra Infurna ([email protected]) on 2019-04-04T10:59:38Z No. of bitstreams: 1 KatiaS_Calabrese_etal_IOC_2008.pdf: 107712 bytes, checksum: 218d62edcf8ffe6857c3d47f249e7030 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-04-04T11:20:28Z (GMT) No. of bitstreams: 1 KatiaS_Calabrese_etal_IOC_2008.pdf: 107712 bytes, checksum: 218d62edcf8ffe6857c3d47f249e7030 (MD5)Made available in DSpace on 2019-04-04T11:20:28Z (GMT). No. of bitstreams: 1 KatiaS_Calabrese_etal_IOC_2008.pdf: 107712 bytes, checksum: 218d62edcf8ffe6857c3d47f249e7030 (MD5) Previous issue date: 2008Universidade Estadual do Maranhão. Departamento de Patologia. São Luis, MA, Brasil.Universidade Estadual do Maranhão. São Luiz, MA, Brasil.Universidade Estadual do Maranhão. São Luiz, MA, Brasil.Universidade Estadual do Maranhão. São Luiz, MA, Brasil.Sem afiliaçãoSem afiliaçãoFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Protozoologia. Rio de Janeiro, RJ, Brasil.Universidade Estadual do Maranhão. Departamento de Patologia. São Luis, MA, Brasil.Universidade Estadual do Maranhão. Departamento de Patologia. São Luis, MA, Brasil.Universidade Estadual do Maranhão. Departamento de Patologia. São Luis, MA, Brasil.The aim of this study was to determine the seroprevalence, clinical and biochemical profile of Leishmania chagasi infection in dogs naturally infected and identify the phlebotominae fauna in an endemic area of São Luis Island. In this present study, 62 household mongrel dogs were sampled for antibodies anti-Leishmania. The seroprevalence was 51.61%. In the clinical evaluation, 36.68% dogs were symptomatic, 38.41% were oligosymptomatic and 26.13% were asymptomatic. The most frequent signs were onychogryphosis and lymphadenomegaly. In 29.41% animals were observed anemia. In the biochemical analysis hepatic function showed changes in relation to alaninoaminotransferase (ALT) and aspartato aminotransferase (AST). Urea values were higher than the references ones for canine specie. The following phlebotominae sandflies were identified: Lutzomyia longipalpis (86.9%), L. evandroi (9.6%), L. choti (2.1%), L. umbratilis (0.7%) e L. whitmani (0.7%)

Os objetos epistêmicos das toxoplasmoses e suas reapresentações em um congresso científico internacional The epistemic objects of toxoplasmoses and their re-presentation in an international scientific conference

O artigo investiga os objetos epistêmicos do Toxoplasma gondii e a correlação de forças de grupos de pesquisa empenhados em reconfigurar a toxoplasmose. A pesquisa de dados e a análise foram conduzidas à luz dos conceitos de 'manipulação' e 'reeencenação', com base na ideia de 'dramatização' proposta por Mol em estudo de filosofia empírica. Constatou-se que os objetos foram reapresentados a partir de matizes diversificados e com forte vinculação ao complexo industrial. Por sua projeção nos rumos da economia mundial no século XXI, a genética foi importante protagonista dos debates sobre causalidade única, uma das convicções da ciência ocidental.<br>The paper investigates the epistemic objects of Toxoplasma gondii and the correlation of forces of research groups committed to redefine or reconfigure toxoplasmosis. The data research and this analysis were conducted in a scientific congress, according to the concepts of 'manipulation' and 'reenactment,' based on the idea of 'dramatization' proposed by Mol in a study of empirical philosophy. It was found that the objects were represented from diversified hues and with strong ties to the industrial complex. For its projection in the trends of the global economy in the twenty-first century, genetics was a major protagonist in the debates on sole causality, one of the convictions of Western science

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe