Abstract: The opportunity to model autism spectrum disorders (ASD) through generation of patient-derived induced pluripotent stem cells (iPSCs) is currently an emerging topic. Wide-scale research of altered brain circuits in syndromic ASD, including Rett Syndrome, Fragile X Syndrome, Angelman's Syndrome and sporadic Schizophrenia, was made possible through animal models. However, possibly due to species differences, and to the possible contribution of epigenetics in the pathophysiology of these diseases, animal models fail to recapitulate many aspects of ASD. With the advent of iPSCs technology, 3D cultures of patient-derived cells are being used to study complex neuronal phenotypes, including both syndromic and nonsyndromic ASD. Here, we review recent advances in using iPSCs to study various aspects of the ASD neuropathology, with emphasis on the efforts to create in vitro model systems for syndromic and nonsyndromic ASD. We summarize the main cellular activity phenotypes and aberrant genetic interaction networks that were found in iPSC-derived neurons of syndromic and nonsyndromic autistic patients.

Abstract: BACKGROUND: While cervical cancer (CC) is an important cause of premature mortality in Colombia, the impact of socio-demographic factors on CC mortality in young women is not well understood. The primary objective of this study was to identify differences in CC mortality among Colombian women aged 20-49 years associated with education, type of health insurance, urban or rural and region of residence, and to determine whether differences in mortality associated with education or insurance varied by age. METHODS: Cervical cancer deaths for 2005-2013 and risk factors were obtained from the National Administrative Department of Statistics. Populations at risk were calculated from age-stratified population projections and the 2010 National and Demographic Health Survey. Negative binomial regression models, stratified by age, were used to examine associations between socio-demographic factors and mortality rates and whether the effects of education and health insurance varied by age. Multiple imputation was used to examine the importance of missing data. RESULTS: Differences of CC mortality were identified among women with limited to no education compared to highly educated women, with the largest disparity in the youngest age group (IRR 26.8, 95 % CI 6.65-108). Differences in mortality associated with health insurance also varied based on age group. Women with contributory and special health insurance had lower mortality rates than women with subsidised or no health insurance, except in the youngest age group. No differences were observed between women with subsidised and those with no insurance in any age group. Mortality rates were high among women who resided in urban areas and in the Atlantic, Central, Pacific, and Amazon-Orinoquia regions of Colombia. Missing values in the mortality database did not impact the findings from this study. CONCLUSIONS: Limited education was most strongly associated with premature CC mortality in the youngest women. Subsidised insurance did not appear to provide significant protection against CC mortality when compared to not having insurance, suggesting the need to examine diagnostic and treatment services available under the subsidised insurance plan. Our results could be used to target interventions to optimise the impact of resources to prevent premature mortality due to CC in Colombia.

Abstract: The role of post-transcriptional gene regulation in human brain development and neurodevelopmental disorders remains mostly uncharacterized. ELAV-like RNA-binding proteins (RNAbps) are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission, both critical to the normal function of the brain in cognition and behavior. Here, we identify the downstream neuronal transcriptional and splicing networks of ELAVL2, an RNAbp with previously unknown function in the brain. Expression of ELAVL2 was reduced in human neurons and RNA-sequencing was utilized to identify networks of differentially expressed and alternatively spliced genes resulting from haploinsufficient levels of ELAVL2. These networks contain a number of autism-relevant genes as well as previously identified targets of other important RNAbps implicated in autism spectrum disorder (ASD) including RBFOX1 and FMRP. ELAVL2-regulated co-expression networks are also enriched for neurodevelopmental and synaptic genes, and include genes with human-specific patterns of expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal function and clinically relevant to ASD.