Generation of an isoform-level transcriptome atlas of macrophage activation.

RNA-seq is routinely used to measure gene expression changes in response to cell perturbation. Genes upregulated or downregulated following some perturbation are designated as genes of interest, and their most expressed isoform(s) would then be selected for follow-up experimentation. However, because of its need to fragment RNA molecules, RNA-seq is limited in its ability to capture gene isoforms and their expression patterns. This lack of isoform-specific data means that isoforms would be selected based on annotation databases that are incomplete, not tissue specific, or do not provide key information on expression levels. As a result, minority or nonexistent isoforms might be selected for follow-up, leading to loss in valuable resources and time. There is therefore a great need to comprehensively identify gene isoforms along with their corresponding levels of expression. Using the long-read nanopore-based R2C2 method, which does not fragment RNA molecules, we generated an Isoform-level transcriptome Atlas of Macrophage Activation that identifies full-length isoforms in primary human monocyte-derived macrophages. Macrophages are critical innate immune cells important for recognizing pathogens through binding of pathogen-associated molecular patterns to toll-like receptors, culminating in the initiation of host defense pathways. We characterized isoforms for most moderately-to-highly expressed genes in resting and toll-like receptor-activated monocyte-derived macrophages, identified isoforms differentially expressed between conditions, and validated these isoforms by RT-qPCR. We compiled these data into a user-friendly data portal within the UCSC Genome Browser (https://genome.ucsc.edu/s/vollmers/IAMA). Our atlas represents a valuable resource for innate immune research, providing unprecedented isoform information for primary human macrophages.

Caráter clínico-epidemiológico e grau de incapacidade física nos portadores de hanseníase no município de Barbacena - MG e macrorregião no período de 2001 a 2010 / Clinical-epidemiological character and degree of disability in patients with Hansen's disease in the municipality of Barbacena - MG and macro-region in the period from 2001 to 2010

Introdução: a hanseníase consiste em uma moléstia potencialmente incapacitante. É uma dermatose infectocontagiosa crônica, causada pelo Mycobacterium leprae, caracterizada por manifestações neurológicas e cutâneas que podem induzir deformidades e mutilações. Apesar de curável, é importante problema de saúde pública, cuja prevalência tem aumentado. Objetivo: caracterizar clínica e epidemiologicamente a hanseníase na macrorregião de Barbacena-MG e determinar a frequência e os graus de incapacidade física dos hansenianos a partir de dados coletados em prontuários. Método: trata-se de estudo qualitativo baseado na descrição estatística dos prontuários examinados e comparação entre paucibacilar (PB) e multibacilar (MB), de corte transversal, de 114 prontuários de pacientes atendidos e registrados pelo SINAN. Resultados: entre os casos de hanseníase notificados, 79,8% eram MB e 20,2% PB, com idade média de 46,0 anos, predomínio masculino, forma clínica dimorfa, com zero a cinco lesões, grau de incapacidade física I e a maioria evoluiu para cura. Entre esses grupos citados houve significância estatística quando comparadas. Conclusão: são necessárias abordagens multidisciplinares do paciente hanseniano. A adesão ao tratamento combate o estigma social, reduz a incidência e minimiza o impacto da doença sobre a vida do indivíduo.

Introduction: Hansen's disease is potentially disabling. It is an infectious and contagious chronic dermatosis caused by Mycobacterium leprae characterized by neurologic and cutaneous manifestations that can induce deformities and mutilations. Although curable, it is an important public health problem with increasing prevalence. Objective: to epidemiologically and clinically characterize leprosy in the macro-region of Barbacena - MG and determine the frequency and degree of physical incapacity of leprosy patients based on data collected in medical records. Method: this was a qualitative study based on the statistical description of medical records examined, paucibacillary (PB) and multibacillary (MB) comparison, and cross-sectional evaluation of 114 medical records of patients tended and recorded at SINAN. Results: among the reported cases of leprosy, 79.8% were MB and 20.2% PB, with an average age of 46.0 years, of predominantly male patients, with the dimorphic clinical form, with zero to five lesions, physical disability grade I, and with most evolving to cure. Comparisons between these groups showed statistical significance. Conclusion: multidisciplinary approaches are needed for Hansen's disease patients. Adherence to treatment combat the social stigma, reduces the incidence, and minimizes disease impact on the individual's life.