PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues

Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the most extensively studied ligand-inducible transcription factors (TFs), able to modulate its transcriptional activity through conformational changes. It is of particular interest because of its pleiotropic functions: it plays a crucial role in the expression of key genes involved in adipogenesis, lipid and glucid metabolism, atherosclerosis, inflammation, and cancer. Its protein isoforms, the wide number of PPARγ target genes, ligands, and coregulators contribute to determine the complexity of its function. In addition, the presence of genetic variants is likely to affect expression levels of target genes although the impact of PPARG gene variations on the expression of target genes is not fully understood. The introduction of massively parallel sequencing platforms—in the Next Generation Sequencing (NGS) era—has revolutionized the way of investigating the genetic causes of inherited diseases. In this context, DNA-Seq for identifying—within both coding and regulatory regions of PPARG gene—novel nucleotide variations and haplotypes associated to human diseases, ChIP-Seq for defining a PPARγ binding map, and RNA-Seq for unraveling the wide and intricate gene pathways regulated by PPARG, represent incredible steps toward the understanding of PPARγ in health and disease

Investigation on MMACHC-R161Q pathological mutant from cblC disease

The cblC disease is a rare inborn disorder of the vitamin B12 (cobalamin, Cbl) metabolism characterized by combined methylmalonic aciduria and homocystinuria. The clinical consequences are devastating and, even when early treated with current therapies, the affected children manifest symptoms involving vision, growth, and learning. The molecular genetic cause of the disease was found in the mutations of the gene coding for MMACHC, a 282 amino acid protein that transports and processes the various forms of Cbl. Here we present the biophysical characterization of wild type MMACHC and a variant, p.R161Q, resulting from the most common missense pathological mutation found in cblC patients. By using a biophysical approach we investigated the stability of the two proteins and their ability to bind and transform the vitamin B12, and to assemble in a dimeric structure. Moreover, interesting indications about the behaviour of the proteins resulted from the Molecular Dynamics (MD) simulations. Overall, our results reveal how a biophysical approach based on the complementarity of computational and experimental methods can offer new insights in the study of the specific effects of the pathological cblC mutation and help prospecting new routes for the cblC treatment

Avaliação do risco de queda em idosos de um centro de convivência / Assessment of the risk of fall in the elderly at a community center

Objetivou-se analisar o risco de quedas em idosos em um Centro de Convivência. Trata-se de um estudo transversal, realizado em um centro de convivência do município de Quixadá-Ceará, com 36 idosos. A coleta de dados ocorreu por meio de um formulário, durante os meses de março a abril de 2018. Os dados foram organizados em um banco de dados e analisados por meio de estatística descritiva. Todos os aspectos éticos foram respeitados. Observou-se que 56% dos idosos eram do sexo feminino, com idade entre 70 a 89 anos, e 64% contavam com um cuidador familiar. A maioria possuía doenças crônicas como hipertensão arterial (75%), diabetes mellitus (38%), problemas osteoarticulares (67%) e doença cardíaca (22%). Verificou-se que 72% dos idosos apresentavam dependência leve e 25% possuíam risco elevado para quedas. Concluiu-se que os idosos do centro de convivência apresentam risco baixo ou moderado para quedas, tornando-se premente a implementação de ações destinadas à promoção da saúde e prevenção de quedas, considerando o potencial de complicações decorrente deste evento

Competências e habilidades de enfermeiros para a promoção da saúde de pacientes em hemodiálise / Competencies and skills of nurses to promote the health of patients on hemodialysis

Objetivou-se identificar as competências do enfermeiro para a promoção da saúde de pacientes em hemodiálise, no período de agosto a setembro de 2015. Trata-se de um estudo descritivo com abordagem qualitativa. O cenário foi um centro de hemodiálise de um hospital de pequeno porte, localizado na cidade de Russas-CE e em outro hospital municipal situado na cidade de Mossoró-RN. Foram identificadas as seguintes competências para a promoção da saúde dos pacientes em hemodiálise: catalisar mudanças, liderança, avaliação das necessidades, planejamento, implementação, avaliação do impacto, defesa e parcerias. Percebeu-se que o enfermeiro deve atentar para a promoção da saúde do paciente com doença renal crônica, de modo a empoderar o paciente para o enfrentamento da doença e tratamento na busca de qualidade de vida

Massive-Scale RNA-Seq Analysis of Non Ribosomal Transcriptome in Human Trisomy 21

Hybridization- and tag-based technologies have been successfully used in Down syndrome to identify genes involved in various aspects of the pathogenesis. However, these technologies suffer from several limits and drawbacks and, to date, information about rare, even though relevant, RNA species such as long and small non-coding RNAs, is completely missing. Indeed, none of published works has still described the whole transcriptional landscape of Down syndrome. Although the recent advances in high-throughput RNA sequencing have revealed the complexity of transcriptomes, most of them rely on polyA enrichment protocols, able to detect only a small fraction of total RNA content. On the opposite end, massive-scale RNA sequencing on rRNA-depleted samples allows the survey of the complete set of coding and non-coding RNA species, now emerging as novel contributors to pathogenic mechanisms. Hence, in this work we analysed for the first time the complete transcriptome of human trisomic endothelial progenitor cells to an unprecedented level of resolution and sensitivity by RNA-sequencing. Our analysis allowed us to detect differential expression of even low expressed genes crucial for the pathogenesis, to disclose novel regions of active transcription outside yet annotated loci, and to investigate a plethora of non-polyadenilated long as well as short non coding RNAs. Novel splice isoforms for a large subset of crucial genes, and novel extended untranslated regions for known genes—possibly novel miRNA targets or regulatory sites for gene transcription—were also identified in this study. Coupling the rRNA depletion of samples, followed by high-throughput RNA-sequencing, to the easy availability of these cells renders this approach very feasible for transcriptome studies, offering the possibility of investigating in-depth blood-related pathological features of Down syndrome, as well as other genetic disorders

Enhancing Conflict Resolution through an AHP-Based Methodology

Opposing interests, bounded rationality and decisional bias may severely hinder conflict resolution. When the commitment for an agreement is high, opponents can resort to the intervention of a third party, such as a mediator. We propose a methodology to enhance conflict resolution, which is based on the analytic hierarchy process (AHP) and takes into account the psychological attitudes of the conflicting parties. The AHP Technique for Highly Eligible Negotiation Agreements (ATHENA) supports a third party in selecting, among potential negotiation agreements, those proposals having the best chances to be accepted by adverse parties. We illustrate an implementation of ATHENA that involved 160 students simulating 'Union versus Management' negotiations. A control group of 40 couples negotiated without any decision support system, while the other 40 couples were supported by ATHENA. The results show that the procedure implementation outperformed unsupported negotiation by increasing the number and the fairness of agreements

Reaching in Depth: Hand Position Dominates over Binocular Eye Position in the Rostral Superior Parietal Lobule

Neural activity was recorded in area PE (dorsorostral part of Brodmann's area 5) of the posterior parietal cortex while monkeys performed arm reaching toward memorized targets located at different distances from the body. For any given distance, arm movements were performed while the animal kept binocular eye fixation constant. Under these conditions, the activity of a large proportion (36%) of neurons was modulated by reach distance during the memory period. By varying binocular eye position ( vergence angle) and initial hand position, we found that the reaching-related activity of most neurons (61%) was influenced by changing the starting position of the hand, whereas that of a smaller, although substantial, population (13%) was influenced by changes of binocular eye position (i.e., by the angle of vergence). Furthermore, the modulation of the neural activity was better explained expressing the reach movement end-point, corresponding to the memorized target location, in terms of distance from the initial hand position, rather than from the body. These results suggest that the activity of neurons in area PE combines information about eye and hand position to encode target distance for reaching in depth predominantly in hand coordinates. This encoding mechanism is consistent with the position of PE in the functional gradient that characterizes the parieto-frontal network underlying reaching