Ensaio sobre o atual padrão de reprodução do capital no Brasil

Este ensaio tem por objetivo analisar um estudo da relação entre a dependência do padrão de reprodução do capital que se configurou nos anos 1990 e se mantém até os dias atuais e a dinâmica da agricultura. O estudo se justifica devido ao fato de que as evidências empíricas da relação entre dependência e agricultura se tornaram cada vez maiores no capitalismo brasileiro nos últimos 30 anos. Esta pesquisa se guiará no âmbito da Teoria Marxista da Dependência e empiricamente serão analisados: (i) a evolução dos marcos regulatórios e da dinâmica institucional pertinente às questões agrícolas e (ii) os dados estatísticos da agricultura disponibilizados pelos órgãos oficiais. Por conseguinte, verifica-se que as inovações nas formas de apropriação de insumos e da produção, nas quais as multinacionais estrangeiras cumprem um papel crucial, reforça e aprofunda os laços de dependência financeira e tecnológica do capitalismo brasileiro

Monodelphis domestica Induced Pluripotent Stem Cells Reveal Metatherian Pluripotency Architecture

Marsupials have been a powerful comparative model to understand mammalian biology. However, because of the unique characteristics of their embryology, marsupial pluripotency architecture remains to be fully understood, and nobody has succeeded in developing embryonic stem cells (ESCs) from any marsupial species. We have developed an integration-free iPSC reprogramming method and established validated iPSCs from two inbred strains of a marsupial, Monodelphis domestica. The monoiPSCs showed a significant (6181 DE-genes) and highly uniform (r2 [95% CI] = 0.973 ± 0.007) resetting of the cellular transcriptome and were similar to eutherian ESCs and iPSCs in their overall transcriptomic profiles. However, monoiPSCs showed unique regulatory architecture of the core pluripotency transcription factors and were more like marsupial epiblasts. Our results suggest that POU5F1 and the splice-variant-specific expression of POU5F3 synergistically regulate the opossum pluripotency gene network. It is plausible that POU5F1, POU5F3 splice variant XM_016427856.1, and SOX2 form a self-regulatory network. NANOG expression, however, was specific to monoiPSCs and epiblasts. Furthermore, POU5F1 was highly expressed in trophectoderm cells, whereas all other pluripotency transcription factors were significantly downregulated, suggesting that the regulatory architecture of core pluripotency genes of marsupials may be distinct from that of eutherians

Human iPSC derived cardiomyocyte model reveals the transcriptomic bases of COVID-19 associated myocardial injury

Background: Multi-organ complications have been the hallmark of severe COVID-19; cardiac injuries were reported in 20% to 30% of hospitalized COVID-19 patients, although the disease etiology remains poorly understood. This study leveraged genome-wide RNA-sequence data generated using induced pluripotent stem cell (iPSC) differentiated cardiomyocytes (CMs) and in vitro modeling of SARS-CoV-2 infection in CMs, to understand the molecular mechanisms of COVID-19 myocardial injuries for novel diagnostic and therapeutic development. Methods: Raw RNA-sequence data sets, GSE165242 and GSE150392 were aligned to human genome assembly GRCh38 and gene expressions were quantified. Differentially expressed (DE) genes between experimental groups were identified using moderated t-statistics (FDR-corrected p-value ≤ 0.05) and Fold-Change analysis (FC absolute ≥ 2.0). Results: A total of 2,148 genes were significantly DE between SARS-CoV-2 infected and vehicle treated CMs and showed significant enrichment in cytokine signaling pathways (p-value=4.89E-25) and regulation of heart contraction (p-value=2.51E-19) gene-ontology biological processes. 606 of these DE genes were significantly upregulated during iPSC to CM differentiation. Disease and function annotation analysis of these 606 genes showed significant enrichment and activation of angiogenesis (p-value=4.04E-23; activation Z-score=3.7) and downregulation of heart contraction and related functions (p-value=4.24E-29; activation Z-score=-2.2) in SARS-CoV-2 infected CMs. The upstream regulator analysis identified upregulation of AGT associated proinflammatory genes and significant downregulation of TBX5 and MYOCD transcription factors and their gene networks, suggesting remodeling of CM contractility architecture. Conclusions: This study identified several AGT associated proinflammatory genes and TBX5 and MYOCD gene networks as potential targets for drug development to address COVID-19 associated cardiac injury

Functional characterization of the iPSC generated hepatocytes using genome-wide transcriptomic analysis

Advances in iPSC technologies now allow us to consider non-invasive large-scale in-vitro disease modeling experiments on disease appropriate cell types in human subjects to better understand human disease pathophysiology, disease genetics and to develop better diagnostic and therapeutic technologies. We performed differential gene expression and functional annotation analysis using genome wide mRNA sequencing data to evaluate the functional and disease modeling potential of iPSC generated hepatocytes. Following the criteria moderated t statistics FDR corrected p-value ≤ 0.05 and fold change-absolute ≥ 2.0, 7,246 genes/transcripts were significantly differentially expressed iPSCs and hepatocytes. The 3,791 of these DE genes/transcripts were significantly upregulated in the hepatocytes and accounted for about 55% of the hepatocytes total expressed transcriptome. The heatmap and principal component analysis suggests a discrete and uniform resetting of cellular transcriptome during iPSC to hepatocyte differentiation. The functional annotation analysis of the 3,791 significantly upregulated hepatocytes genes/transcripts showed significant enrichment hepatocytes associated cellular functions and canonical pathways. The gene known to be associated with various common human liver disorders and toxicities were also significantly enriched in hepatocytes upregulated 3,791 genes/transcripts. These results suggest that iPSC generated hepatocytes have a functional profile very similar to human primary hepatocytes and are suitable for in-vitro modeling of human liver disorders and toxicities

Disease Modeling and Disease Gene Discovery in Cardiomyopathies: A Molecular Study of Induced Pluripotent Stem Cell Generated Cardiomyocytes

The in vitro modeling of cardiac development and cardiomyopathies in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) provides opportunities to aid the discovery of genetic, molecular, and developmental changes that are causal to, or influence, cardiomyopathies and related diseases. To better understand the functional and disease modeling potential of iPSC-differentiated CMs and to provide a proof of principle for large, epidemiological-scale disease gene discovery approaches into cardiomyopathies, well-characterized CMs, generated from validated iPSCs of 12 individuals who belong to four sibships, and one of whom reported a major adverse cardiac event (MACE), were analyzed by genome-wide mRNA sequencing. The generated CMs expressed CM-specific genes and were highly concordant in their total expressed transcriptome across the 12 samples (correlation coefficient at 95% CI =0.92 ± 0.02). The functional annotation and enrichment analysis of the 2116 genes that were significantly upregulated in CMs suggest that generated CMs have a transcriptomic and functional profile of immature atrial-like CMs; however, the CMs-upregulated transcriptome also showed high overlap and significant enrichment in primary cardiomyocyte (p-value = 4.36 × 10−9), primary heart tissue (p-value = 1.37 × 10−41) and cardiomyopathy (p-value = 1.13 × 10−21) associated gene sets. Modeling the effect of MACE in the generated CMs-upregulated transcriptome identified gene expression phenotypes consistent with the predisposition of the MACE-affected sibship to arrhythmia, prothrombotic, and atherosclerosis risk

Human monocyte-derived macrophage responses to M. tuberculosis differ by the host’s tuberculosis, diabetes or obesity status, and are enhanced by rapamycin

Human macrophages play a major role in controlling tuberculosis (TB), but their anti-mycobacterial mechanisms remain unclear among individuals with metabolic alterations like obesity (TB protective) or diabetes (TB risk). To help discern this, we aimed to: i) Evaluate the impact of the host’s TB status or their comorbidities on the anti-mycobacterial responses of their monocyte-derived macrophages (MDMs), and ii) determine if the autophagy inducer rapamycin, can enhance these responses. We used MDMs from newly diagnosed TB patients, their close contacts and unexposed controls. The MDMs from TB patients had a reduced capacity to activate T cells (surrogate for antigen presentation) or kill M. tuberculosis (Mtb) when compared to non-TB controls. The MDMs from obese participants had a higher antigen presenting capacity, whereas those from chronic diabetes patients displayed lower Mtb killing. The activation of MDMs with rapamycin led to an enhanced anti-mycobacterial activity irrespective of TB status but was not as effective in patients with diabetes. Further studies are warranted using MDMs from TB patients with or without metabolic comorbidities to: i) elucidate the mechanisms through which host factors affect Mtb responses, and ii) evaluate host directed therapy using autophagy-inducing drugs like rapamycin to enhance macrophage function

Non-alcoholic fatty liver disease and hepatocellular carcinoma risk associated gene expression phenotypes in Hispanics

Background: Non-alcoholic fatty liver disease (NAFLD) is a state of metabolic dysregulation characterized by excessive lipid accumulation into the hepatocytes (hepatic steatosis). It is a major determinant of risk for hepatocellular carcinoma (HCC). Hispanics in south Texas exhibit one of the highest incidences of NAFLD and HCC in the United States. Methods: We used an induced pluripotent stem cell (iPSC) based hepatocyte (HEP) model to identify high lipid stress induced transcriptomic changes in HEPs to better understand hepatic steatosis associated HCC risk. Well-characterized, iPSC differentiated functional HEPs generated from six participants in our San Antonio Mexican American family study were challenged with high lipid conditions in in-vitro culture. The lipid challenged and vehicle treated HEPs were then analyzed for cellular lipid accumulation, fibrosis, and genome wide gene expression by mRNA-sequencing. Results: Quantitative measures of cellular neutral lipids and fibrosis marker (COL1A1) were significantly increased in lipid challenged HEPs. These measures also showed a high correlation (r2 ≥70%) with individual’s in-vivo liver fat. Genome wide differential gene expression analysis identified 78 genes that were significantly differentially expressed (DE) between lipid challenged and vehicle treated HEPs. Functional annotation analysis showed significant enrichment of DE genes in liver hyperplasia/hyperproliferation functions (27 genes; p-value 2.0x10-2 to 9.2x10-2), and included several genes (PDRG1, PLIN2, CFHR3, ANXA2P3, HBA1, HBA2, HBB) whose altered expression was shown to be associated with HCC risk. Conclusions: We have identified several genes associated with risk for HCC for which expression was significantly dysregulated by a high lipid stress challenge in HEPs

Role of miRNA-mRNA Interaction in Neural Stem Cell Differentiation of Induced Pluripotent Stem Cells

miRNA regulates the expression of protein coding genes and plays a regulatory role in human development and disease. The human iPSCs and their differentiated progenies provide a unique opportunity to identify these miRNA-mediated regulatory mechanisms. To identify miRNA–mRNA regulatory interactions in human nervous system development, well characterized NSCs were differentiated from six validated iPSC lines and analyzed for differentially expressed (DE) miRNome and transcriptome by RNA sequencing. Following the criteria, moderated t statistics, FDR-corrected p-value ≤ 0.05 and fold change—absolute (FC-abs) ≥2.0, 51 miRNAs and 4033 mRNAs were found to be significantly DE between iPSCs and NSCs. The miRNA target prediction analysis identified 513 interactions between 30 miRNA families (mapped to 51 DE miRNAs) and 456 DE mRNAs that were paradoxically oppositely expressed. These 513 interactions were highly enriched in nervous system development functions (154 mRNAs; FDR-adjusted p-value range: 8.06 × 10−15–1.44 × 10−4). Furthermore, we have shown that the upregulated miR-10a-5p, miR-30c-5p, miR23-3p, miR130a-3p and miR-17-5p miRNA families were predicted to down-regulate several genes associated with the differentiation of neurons, neurite outgrowth and synapse formation, suggesting their role in promoting the self-renewal of undifferentiated NSCs. This study also provides a comprehensive characterization of iPSC-generated NSCs as dorsal neuroepithelium, important for their potential use in in vitro modeling of human brain development and disease

Who's Cueing Whom? Mass-elite linkages and the future of European integration

The 2005 French and Dutch referendum campaigns were characterized by an alleged disconnect between pro-European political elites and Eurosceptic masses. Past evidence regarding elite-mass linkages in the context of European integration has been conflicting. Whereas some scholars argue that political elites respond to the changing preferences of their electorates, others suggest that party elites cue the mass public through a process of information and persuasion. We contend that these conflicting results stem from the reciprocal nature of elite-mass linkages and estimate a series of dynamic simultaneous equations models to account for this reverse causation. Using Euro-barometer and expert survey data from 1984-2002, we find evidence of a dual-process model, whereby party elites both respond to and shape the views of their supporters. We also find that the strength of these results is contingent on several factors, including the type of electoral system, intra-party dissent and voter characteristics. Copyright © 2007 Sage Publications

Collaborative fisheries research reveals reserve size and age determine efficacy across a network of marine protected areas

A variety of criteria may influence the efficacy of networks of marine protected areas (MPA) designed to enhance biodiversity conservation and provide fisheries benefits. Meta-analyses have evaluated the influence of MPA attributes on abundance, biomass, and size structure of harvested species, reporting that MPA size, age, depth, and connectivity influence the strength of MPA responses. However, few empirical MPA evaluation studies have used consistent sampling methodology across multiple MPAs and years. Our collaborative fisheries research program systematically sampled 12 no-take or highly protective limited-take MPAs and paired fished reference areas across a network spanning 1100 km of coastline to evaluate the factors driving MPA efficacy across a large geographic region. We found that increased size and age consistently contributed to increased fish catch, biomass, and positive species responses inside MPAs, while accounting for factors such as latitude, primary productivity, and distance to the nearest MPA. Our study provides a model framework to collaboratively engage diverse stakeholders in fisheries research and provide high-quality data to assess the success of conservation strategies