Sex-dependent diversity in ventral tegmental dopaminergic neurons and developmental programing: a molecular, cellular and behavioral analysis

The knowledge that diverse populations of dopaminergic neurons within the ventral tegmental area (VTA) can be distinguished in terms of their molecular, electrophysiological and functional properties, as well as their differential projections to cortical and subcortical regions has significance for key brain functions, such as the regulation of motivation, working memory and sensorimotor control. Almost without exception, this understanding has evolved from landmark studies performed in the male sex. However, converging evidence from both clinical and pre-clinical studies illustrates that the structure and functioning of the VTA dopaminergic systems are intrinsically different in males and females. This may be driven by sex differences in the hormonal environment during adulthood ('activational' effects) and development (perinatal and/or pubertal 'organizational' effects), as well as genetic factors, especially the SRY gene on the Y chromosome in males, which is expressed in a sub-population of adult midbrain dopaminergic neurons. Stress and stress hormones, especially glucocorticoids, are important factors which interact with the VTA dopaminergic systems in order to achieve behavioral adaptation and enable the individual to cope with environmental change. Here, also, there is male/female diversity not only during adulthood, but also in early life when neurobiological programing by stress or glucocorticoid exposure differentially impacts dopaminergic developmental trajectories in male and female brains. This may have enduring consequences for individual resilience or susceptibility to pathophysiological change induced by stressors in later life, with potential translational significance for sex bias commonly found in disorders involving dysfunction of the mesocorticolimbic dopaminergic systems. These findings highlight the urgent need for a better understanding of the sexual dimorphism in the VTA if we are to improve strategies for the prevention and treatment of debilitating conditions which differentially affect men and women in their prevalence and nature, including schizophrenia, attention/deficit hyperactivity disorder, autism spectrum disorders, anxiety, depression and addiction

Phase 1 clinical trial of live attenuated Shigella dysenteriae type-1 DeltaicsA Deltaent Deltafep DeltastxA:HgR oral vaccine SC599 in healthy human adult volunteers

Twenty-eight adults received between 10(2) and 10(8)colony forming units of live Shigella dysenteriae type-1 vaccine SC599, attenuated by deletion of invasion (icsA), iron chelation (ent, fep) and shiga toxin A-subunit (stxA) genes, followed by ciprofloxacin on day 4. Dose-independent diarrhea or change in bowel habit was seen in 3 subjects, without dysentery, vaccinaemia or serious adverse events. Hematology and biochemical parameters were unchanged. Doses of 10(5) or greater induced dose-independent SD1 lipopolysaccharide-specific antibody secreting cell (ASC) responses. Geometric mean number of IgA ASCs per 10(6) PBMCs for 10(5), 10(6), 10(7) and 10(8) groups were respectively 41, 8.8, 26 and 8.5. Serum antibody responses were seen in three subjects. SC599 appears immunogenic with maximum tolerated dose greater than 10(8)CFU

Seed research for improved technologies Pesquisa para o aprimoramento de tecnologia de sementes

The production of high-quality seed is the basis for a durable a profitable agriculture. After production, seed is processed, conditioned, stored, shipped and germinated. For quality assurance, seed quality has to be controlled at all steps of the production chain. Seed functioning is accompanied by programmed transitions from cell proliferation to quiescence upon maturation and from quiescence to reinitiation of cellular metabolism upon imbibition. Despite the obvious importance of these control mechanisms, very little information is available at the molecular level concerning those elements that regulate seed germination. In the present study, the induction of cell cycle activity and the regulation of ß-tubulin expression is related to the water content and other physical properties of the seed.<br>A produção de sementes de alta qualidade é a base para uma agricultura produtiva. Após a colheita, a semente é beneficiada, embalada, armazenada, transportada e semeada. Para maior segurança, tanto dos produtores como dos consumidores, a qualidade da semente deve ser mantida sob controle em todas as fases do processo de produção. O desempenho da semente é resultado de transições programadas desde a divisão celular até a quiescência, durante a maturação, e da quiescência até o reinicio do metabolismo celular, durante a embebição. Apesar da importância destes mecanismos de controle, há pouca informação disponível, a nível molecular, no que diz respeito aos elementos que regulam a germinação da semente. No presente trabalho, a indução do ciclo de atividade celular e a regulação da expressão de ß-tubulina são relacionadas ao grau de umidade e a outras propriedades físicas da semente