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Ashraf S. Yousif Larance Ronsard Pankaj Shah Tatsushi Omatsu Maya Sangesland Thalia Bracamonte Moreno Evan C. Lam Vladimir D. Vrbanac Alejandro B. Balazs Hans-Christian Reinecker Daniel Lingwood 《Immunity》2021,54(2):235-246.e5
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3.
Studies of children and adolescents with conduct problems suggest both genetic and environmental influences on population variance. Any genetic influence is likely to be complex and to act via mediating attributes of personality or cognitive style. One potential mediating attribute is social cognitive ability, as conduct problems have been shown to be associated with deficient social cognitive skills. The current investigation has examined the correlation between conduct problems and social cognition and has investigated the genetic and environmental influences on these measures and their covariation using a twin design. A population-based sample of twins aged 5-17 was used to examine the genetic relationship between conduct problems and social cognition using parent-report questionnaires. Conduct problems and social cognition were found to be highly correlated and to share common genetic influences that accounted for about half the covariation in scores. Each phenotype was subject to its own environmental influences that were not shared. 相似文献
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Renan Faustino Fabiana Rabe Carvalho Thalia Medeiros Dbora Familiar-Macedo Renata Artimos de Oliveira Vianna Paulo Emílio Crrea Leite Isabela Resende Pereira Claudete Aparecida Araújo Cardoso Elzinandes Leal De Azeredo Andrea Alice Silva 《Viruses》2022,14(9)
Chikungunya virus (CHIKV) vertical transmission occurs due to maternal viremia in the prepartum. Clinical presentation in neonates can be varied; however, the consequences of intrauterine exposure on the immune response are unclear. Thus, we aimed to analyze inflammatory alterations in children exposed to maternal CHIKV infection. This is a cross-sectional study that included children exposed to maternal CHIKV infection (confirmed by RT-qPCR and/or IgM). Circulant immune mediators were analyzed by a multiplex assay. RESULTS: We included 33 children, with a mean age of 3 ± 2.9 months-old, and 19 (57.6%) were male. Only one child presented neurological alterations. CHIKV-exposed infants showed elevated levels of MIP-1α, MIP-1β, and CCL-2 (p < 0.05). Pro-inflammatory cytokines such as TNFα, IL-6, and IL-7 (p < 0.0001) were also increased. In addition, lower levels of PDGF-BB and GM-CSF were observed in the same group (p < 0.0001). Principal component (PC) analysis highlighted a distinction in the inflammatory profile between groups, where PC explained 56.6% of the alterations. Our findings suggest that maternal exposure to CHIKV can affect the circulating levels of pro-inflammatory cytokines during the infants’ first year of life. The long-term clinical consequences of these findings should be investigated. 相似文献
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OBJECTIVE: A large body of data suggests that pertussis toxin (PTX)-sensitive G protein signals in mature and immature hemopoietic cells control their migration patterns in vitro and in vivo. These effects were derived after treatment of cells or animals with PTX. To circumvent several inherent problems of PTX holotoxin treatment, we expressed the S1 catalytic activity of PTX, thus blocking Gi protein signaling, in 32D murine myeloid progenitor cells and in primary human CD34+ cells, and studied its functional consequences. METHODS: S1 was expressed using viral vectors. Effects of Gi protein blockade on proliferation, migration, adhesion, and gene expression were tested in vitro. RESULTS: S1 expression was nontoxic for the cells; expression and function were stable long-term and not overridden by compensatory mechanisms. S1-transduced 32D cells and primary CD34+ cells migrated poorly and did not contract their cytoskeleton upon treatment with the chemoattractant stromal cell-derived factor -1 (SDF-1), similar to the phenotype induced by PTX treatment. Gene expression studies comparing S1-transduced and control 32D cells uncovered four genes, expression of which was regulated by Gi protein blockade. Of interest, although SDF-1 signaling was inhibited, comparison between SDF-1-treated and untreated cells suggests that SDF-1 stimulation does not depend on de novo gene expression in these cells. Furthermore, when injected into nonobese diabetic/severe combined immunodeficient mice, seeding of S1-expressing 32D cells to bone marrow was largely blocked. CONCLUSION: Expression of S1 is an effective approach for studying long-term functional consequences of Gi protein blockade in hemopoietic cells in vitro and in vivo. 相似文献
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Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells. 总被引:11,自引:8,他引:11
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Elizabeth A Sweeney Hugues Lortat-Jacob Gregory V Priestley Betty Nakamoto Thalia Papayannopoulou 《Blood》2002,99(1):44-51
It was previously reported that treatment with the sulfated polysaccharide fucoidan or the structurally similar dextran sulfate increased circulating mature white blood cells and hematopoietic progenitor/stem cells (HPCs) in mice and nonhuman primates; however, the mechanism mediating these effects was unclear. It is reported here that plasma concentrations of the highly potent chemoattractant stromal-derived factor 1 (SDF-1) increase rapidly and dramatically after treatment with fucoidan in monkeys and in mice, coinciding with decreased levels in bone marrow. In vitro and in vivo data suggest that the SDF-1 increase is due to its competitive displacement from heparan sulfate proteoglycans that sequester the chemokine on endothelial cell surfaces or extracellular matrix in bone marrow and other tissues. Although moderately increased levels of interleukin-8, MCP1, or MMP9 were also present after fucoidan treatment, studies in gene-ablated mice (GCSFR(-/-), MCP1(-/-), or MMP9(-/-)) and the use of metalloprotease inhibitors do not support their involvement in the concurrent mobilization. Instead, SDF-1 increases, uniquely associated with sulfated glycan-mobilizing treatments and not with several other mobilizing agents tested, are likely responsible. To the authors' knowledge, this is the first published report of disrupting the SDF-1 gradient between bone marrow and peripheral blood through a physiologically relevant mechanism, resulting in mobilization with kinetics similar to other mobilizing CXC chemokines. The study further underscores the importance of the biological roles of carbohydrates. 相似文献
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Extended Sedation With Continuous Midazolam or Dexmedetomidine Infusion for Young Children Receiving 131I‐MIBG Radiopharmaceutical Therapy for Advanced Neuroblastoma
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Andria Veras Gonalves Demcrito de B. Miranda-Filho Líbia Cristina Rocha Vilela Regina Coeli Ferreira Ramos Thalia V. B. de Araújo Rmulo A. L. de Vasconcelos Maria Angela Wanderley Rocha Sophie Helena Eickmann Marli Tenrio Cordeiro Liana O. Ventura Ulisses Ramos Montarroyos Alessandra Mertens Brainer Maria Durce Costa Gomes Paula Fabiana Sobral da Silva Celina M. T. Martelli Elizabeth B. Brickley Ricardo A. A. Ximenes 《Viruses》2021,13(1)
Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common—and clinically important—endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary. 相似文献