Different rhythms of health biotechnology development in Brazil and Cuba

Biotechnology is typically associated with the centres of learning and firms in industrialised countries but usually not with institutions in developing countries. Developing nations are however, becoming active in this field and are increasingly using recombinant methods to produce new and innovative health products for their populations. Here we will examine health biotechnology development in two developing countries, Brazil and Cuba. We will compare the major characteristics of their health biotechnology sectors and highlight factors that have shaped their development in order to understand better what main factors and conditions can promote health biotechnology innovation in developing countries

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Desynchronization in Networks of Globally Coupled Neurons with Dendritic Dynamics

Effective desynchronization can be exploited as a tool for probing the functional significance of synchronized neural activity underlying perceptual and cognitive processes or as a mild treatment for neurological disorders like Parkinson’s disease. In this article we show that pulse-based desynchronization techniques, originally developed for networks of globally coupled oscillators (Kuramoto model), can be adapted to networks of coupled neurons with dendritic dynamics. Compared to the Kuramoto model, the dendritic dynamics significantly alters the response of the neuron to the stimulation. Under medium stimulation amplitude a bistability of the re- sponse of a single neuron is observed. When stimulated at some initial phases, the neuron displays only modulations of its firing, whereas at other initial phases it stops oscillating entirely. Significant alterations in the duration of stimulation-induced transients are also observed. These transients endure after the end of the stimulation and cause maximal desynchronization to occur not during the stimulation, but with some delay after the stimulation has been turned off. To account for this delayed desynchronization effect, we have designed a new calibration procedure for finding the stimulation parameters that result in optimal desynchronization. We have also developed a new desynchronization technique by low frequency entrainment. The stimulation techniques originally developed for the Kuramoto model, when using the new calibration procedure, can also be applied to networks with dendritic dynamics. However, the mechanism by which desynchronization is achieved is substantially different than for the network of Kuramoto oscillators. In particular, the addition of dendritic dynamics significantly changes the timing of the stimulation required to obtain desynchronization. We propose desynchronization stimulation for experimental analysis of synchronized neural processes and for the therapy of movement disorders

Migration and urban schistosomiasis. The case of São Lourenço da Mata, Northeast of Brazil Migração e esquistossomose urbana. O caso de São Lourenço da Mata, Nordeste do Brasil

A population-based case-control design was used to investigate the association between migration, urbanisation and schistosomiasis in the Metropolitan Region of Recife, Northeast of Brazil. 1022 cases and 994 controls, aged 10 to 25, were selected. The natives and the migrants who come from endemic areas have a similar risk of infection. On the other hand, the risk of infection of migrants from nonendemic areas seems to be related with the time elapsed since their arrival in São Lourenço da Mata; those who have been living in that urban area for 5 or more years have a risk of infection similar to that of the natives. Those arriving in the metropolitan region of Recife mostly emigrate from "zona da mata" and "zona do agreste" in the state of Pernambuco. Due to the changes in the sugar agro-industry and to the increase in the area used for cattle grazing these workers were driven to villages and cities. The pattern of urbanisation created the conditions for the establishment of foci of transmission in São Lourenço da Mata.<br>Um estudo de caso-controle de base populacional foi desenvolvido para estudar a associação entre migração, urbanização e esquistossomose na Região Metropolitana do Recife, Nordeste do Brasil. Foram selecionados 1022 casos e 994 controles no grupo etário de 10 a 25 anos. Observou-se que os nativos e os migrantes que são provenientes de áreas endêmicas tem um risco semelhante de infecção. Por outro lado, o risco de infecção em migrantes não originários de áreas endêmicas parece estar relacionado com o tempo decorrido desde sua chegada em São Lourenço da Mata; aqueles que estão morando nessa área urbana por um período igual ou superior a cinco anos tem um risco de infeção semelhante ao dos nativos. As mudanças na indústria agro-açucareira na Zona da Mata e a expansão das áreas de criação de gado no Agreste impeliram os trabalhadores rurais a se deslocar para vilarejos e cidades. O padrão de urbanização que ocorreu em São Loureço da Mata criou as condições propícias para que se estabelecessem focos de transmissão