Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders

As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle–brain, liver–brain and gut–brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise–brain communication and their benefits for physiology and brain function.     

Provision of mental health services in women's health centers

Women's health centers are often associated with a comprehensive model of health care that treats the "whole woman." Using data from a nationwide study of 467 women's health centers, we explored how the ideal of comprehensive care was implemented with respect to mental health services. Specifically, we examined the rates of screening and treatment for a subset of mental health and behavioral and social problems in women's health centers and the structural, staffing, philosophical, and patient factors associated with the provision of services. Across 12 services, the overall rates of provision ranged from 7.7% for screening for dementing disorders to 27.6% for smoking cessation counseling and treatment. In a series of logistic regressions, center type (primary care) and having a mental health staff person were consistently associated with service provision; other important variables were having a high percentage of women using the center as their usual source of care and having a belief in women-centered care. Findings indicate that the majority of women using women's health centers do not receive services in a comprehensive care environment that includes key mental health services.     

Domain flexibility in retroviral proteases: structural implications for drug resistant mutations

Rigid body rotation of five domains and movements within their interfacial joints provide a rational context for understanding why HIV protease mutations that arise in drug resistant strains are often spatially removed from the drug or substrate binding sites. Domain motions associated with substrate binding in the retroviral HIV-1 and SIV proteases are identified and characterized. These motions are in addition to closure of the flaps and result from rotations of approximately 6-7 degrees at primarily hydrophobic interfaces. A crystal structure of unliganded SIV protease (incorporating the point mutation Ser 4 His to stabilize the protease against autolysis) was determined to 2.0 A resolution in a new space group, P3221. The structure is in the most "open" conformation of any retroviral protease so far examined, with six residues of the flaps disordered. Comparison of this and unliganded HIV structures, with their respective liganded structures by difference distance matrixes identifies five domains of the protease dimer that move as rigid bodies against one another: one terminal domain encompassing the N- and C-terminal beta sheet of the dimer, two core domains containing the catalytic aspartic acids, and two flap domains. The two core domains rotate toward each other on substrate binding, reshaping the binding pocket. We therefore show that, for enzymes, mutations at interdomain interfaces that favor the unliganded form of the target active site will increase the off-rate of the inhibitor, allowing the substrate greater access for catalysis. This offers a mechanism of resistance to competitive inhibitors, especially when the forward enzymatic reaction rate exceeds the rate of substrate dissociation.     

All that you can be: stereotyping of self and others in a military context

The authors tested the shifting standards model (M. Biernat, M. Manis, & T. E. Nelson, 1991) as it applies to sex- and race-based stereotyping of self and others in the military. U. S. Army officers attending a leadership training course made judgments of their own and their groupmates' leadership competence at 3 time points over a 9-week period. We examined the effects of officer sex and race on both subjective (rating) and objective/common-rule (ranking/Q-sort) evaluations. Stereotyping generally increased with time, and in accordance with the shifting standards model, pro-male judgment bias was more evident in rankings than in ratings, particularly for White targets. Self-judgments were also affected by sex-based shifting standards, particularly in workgroups containing a single ("solo") woman. Differential standard use on the basis of race was less apparent, a finding attributed to the Army's explicit invocation against the use of differential race-based standards.     

Analogues of capsaicin with agonist activity as novel analgesic agents: structure-activity studies. 4. Potent, orally active analgesics

Structural features of three regions of the capsaicin molecule necessary for agonist properties were delineated by a previously reported modular approach. These in vitro agonist effects were shown to correlate with analgesic potency in rodent models. Combination of optimal structural features from each of these regions of the capsaicin molecule have led to highly potent agonists (eg., 1b). Evaluation in vivo established that 1b had analgesic properties but poor oral activity, short duration of action, and excitatory side effects which precluded further development of this compound. Preliminary metabolism studies had shown that the phenol moiety of 1b was rapidly glucuronidated in vivo, providing a possible explanation for the poor pharmacokinetic profile. Subsequent specific modification of the phenol group led to compounds 2a-j, which retained in vitro potency. The in vivo profiles of two representatives of this series, 2a,h, were much improved over the "parent" phenol series, and they are candidates for development as analgesic agents.     

Roald Amundsen--a study of personality

Roald Amundsen is the most famous of the Norwegian polar explorers. His ancestors came from a group of islands south-east of the Oslofjord. From being fishermen and sailors, they progressed to becoming captains and shipowners in the course of two generations. Amundsen's father, Jens, stayed at sea until his ship went down with all the crew. Roald was 14 years of age at the time, the youngest of four competing brothers. Jens had left the close-knit local family community before that, and bought a flat in the capital, Oslo, so that his sons could get a better education. Roald's mother wanted him to study medicine. He did as she wished for a time, but was not at all interested. When his mother died, he abruptly left the university and went to sea, which had been the tradition in his family for decades. As a young boy he was an admirer of Sir John Franklin and his explorers of the Northwest Passage. Fridtjof Nansen became his ideal. The biographies about Roald Amundsen are very diverging--some hold him a hero, others reflect a strongly critical attitude. Here, the author tries to define his personality and places him firmly within the narcissistic domain. His tendency to seek the company of married women, but to take immediate flight when they really became interested reflects an Oedipus complex from before puberty. The tragic death of his father, the sea captain, may have been a supposition; puberty can be seen as a period of coping with ambivalence towards an earlier idealized father. His genius combined ambitious goals with a sharp eye for details as regards the equipment used in his expeditions. In his travels in the Arctic and the Antartic he was driven forward by the energy of the nation. His heroic death, trying to save his earlier "enemy", Nobile, was probably caused by an urge for self-destruction.     

CHL1 encodes a component of the low-affinity nitrate uptake system in Arabidopsis and shows cell type-specific expression in roots

The Arabidopsis CHL1 (AtNRT1) gene confers sensitivity to the herbicide chlorate and encodes a nitrate-regulated nitrate transporter. However, how CHL1 participates in nitrate uptake in plants is not yet clear. In this study, we examined the in vivo function of CHL1 with in vivo uptake measurements and in situ hybridization experiments. Under most conditions tested, the amount of nitrate uptake by a chl1 deletion mutant was found to be significantly less than that of the wild type. This uptake deficiency was reversed when a CHL1 cDNA clone driven by the cauliflower mosaic virus 35S promoter was expressed in transgenic chl1 plants. Furthermore, tissue-specific expression patterns showed that near the root tip, CHL1 mRNA is found primarily in the epidermis, but further from the root tip, the mRNA is found in the cortex or endodermis. These results are consistent with the involvement of CHL1 in nitrate uptake at different stages of root cell development. A functional analysis in Xenopus oocytes indicated that CHL1 is a low-affinity nitrate transporter with a K(m) value of approximately 8.5 mM for nitrate. This finding is consistent with the chlorate resistance phenotype of chl1 mutants. However, these results do not fit the current model of a single, constitutive component for the low-affinity uptake system. To reconcile this discrepancy and the complex uptake behavior observed, we propose a "two-gene" model for the low-affinity nitrate uptake system of Arabidopsis.     

Building a database for product design knowledge retrieval—A case study in robotic design database

In product design process, when dealing with technical problems or initiating a new design, R&D personnel would often turn to technical database to seek inspiration. The building of a database with such documents has not been systematically dealt with. In this paper, several issues on how to build up a product design database are investigated: input source, sampling scheme and quality control. A case study of building a database for robotic design is used to demonstrate the concept. It is an archive of more than 1500 relevant technical papers. A total of 16 graduates are employed as operators in the labeling process and subsequently the hypothesis tests are utilized to process the labeling results. To ensure this database quality, the labeling consistency of each operator and the understanding of each category are tested. With the use of statistical methods, this work proposes a feasible and practical way to create such a database for product design.