Biology subjects

Figueiredo, C.

Publications and source records attributed to Figueiredo, C..

3 recordsLinked to original sources

bioRxiv2017

Neonatal Zika virus infection causes epileptic seizures, viral persistence and long-term behavioral impairment

A causal relationship between congenital Zika virus (ZIKV) exposure and microcephaly and other neurological disorders have been established, but long-term consequences of infection are still unknown. We evaluated acute and late neuropathological and behavioral consequences of ZIKV infection in a neonatal immunocompetent mouse model. ZIKV showed brain tropism, causing post-natal microcephaly and several behavioral dysfunctions. During the acute phase of infection, mice developed very frequent epileptic seizures, which are consistently reduced by TNF- neutralization. Although adult animals recover from seizures, they become more susceptible to chemically-induced crises. Intriguingly, the virus remained actively replicating in adult animals, which show persistent necrosis and calcifications in the mice brain. Altogether the results reveal late consequences of neonatal ZIKV exposure and suggest the early inhibition of neuroinflammation as a potential treatment.

neuroscience↗

bioRxiv2017

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women due to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumours. 75% of breast cancer patients show activation of Insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in a pre-clinical breast cancer model compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation.

cancer biology↗

bioRxiv2017

Genome-wide association study of asthma in individuals of African ancestry reveals novel asthma susceptibility loci

BACKGROUNDAsthma is a complex disease with striking disparities across racial and ethnic groups, which may be partly attributable to genetic factors. One of the main goals of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to discover genes conferring risk to asthma in populations of African descent.\n\nMETHODSWe performed a genome-wide meta-analysis of asthma across 11 CAAPA datasets (4,827 asthma cases and 5,397 controls), genotyped on the African Diaspora Power Chip (ADPC) and including existing GWAS array data. The genotype data were imputed up to a whole genome sequence reference panel from n=880 African ancestry individuals for a total of 61,904,576 SNPs. Statistical models appropriate to each study design were used to test for association, and results were combined using the weighted Z-score method. We also used admixture mapping as a complementary approach to identify loci involved in asthma pathogenesis in subjects of African ancestry.\n\nRESULTSSNPs rs787160 and rs17834780 on chromosome 2q22.3 were significantly associated with asthma (p=6.57 x 10-9 and 2.97 x 10-8, respectively). These SNPs lie in the intergenic region between the Rho GTPase Activating Protein 15 (ARHGAP15) and Glycosyltransferase Like Domain Containing 1 (GTDC1) genes. Four low frequency variants on chromosome 1q21.3, which may be involved in the \"atopic march\" and which are not polymorphic in Europeans, also showed evidence for association with asthma (1.18 x10-6 [≤] p [≤] 3.06 x10-6). SNP rs11264909 on chromosome 1q23.1, close to a region previously identified by the EVE asthma meta-analysis as having a putative African ancestry specific effect, only showed differences in counts in subjects homozygous for alleles of African ancestry. Admixture mapping also identified a significantly associated region on chromosome 6q23.2, which includes the Transcription Factor 21 (TCF21) gene, previously shown to be differentially expressed in bronchial tissues of asthmatics and non-asthmatics.\n\nCONCLUSIONSWe have identified a number of novel asthma association signals warranting further investigation.

bioinformatics↗