Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Limnological changes in Dom Helvécio Lake (South-East Brazil): natural and anthropogenic causes

In order to verify changes in physical, chemical and biological features of Dom Helvécio Lake (South-East Brazil), this study compares previous and recent data obtained from limnological investigations over three decades. Plankton species composition and density together with environmental data from 1978, 1983, and during 1999 to 2006 showed changes driven by seasonal climatic forces or by anthropogenic causes. Changes in diversity are shown as a consequence of alternation of rainy and dry periods and introduction of exotic fish species. Finally, suggestions are made for improving conservation efforts in the area, through planned actions and monitoring programmes.</jats:p

Functional performance and social relations among the elderly in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil: a population-based epidemiological study

This study was conducted in a probabilistic sam- ple of 2,055 elderly in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil, to examine components of social network (conjugal status and visits by the children, other relatives, and friends) and social support (satisfaction with personal relations and having persons on whom to rely) associated with limitations in performing basic activities of daily living (ADL). Multivariate analysis used the Hurdle model. Performance of ADL showed independent and statistically significant associations with social network (fewer meetings with friends and not having children) and personal support (dissatisfaction/indifference towards personal relations). These associations remained after adjusting for social and demographic characteristics, health status, and other indicators of social relations. Our results emphasize the need for greater attention to social network and social support for elderly with functional limitations and those with weak social networks and social support

Decentralization's impact on the health workforce: Perspectives of managers, workers and national leaders

Designers and implementers of decentralization and other reform measures have focused much attention on financial and structural reform measures, but ignored their human resource implications. Concern is mounting about the impact that the reallocation of roles and responsibilities has had on the health workforce and its management, but the experiences and lessons of different countries have not been widely shared. This paper examines evidence from published literature on decentralization's impact on the demand side of the human resource equation, as well as the factors that have contributed to the impact. The elements that make such an impact analysis exceptionally complex are identified. They include the mode of decentralization that a country is implementing, the level of responsibility for the salary budget and pay determination, and the civil service status of transferred health workers. The main body of the paper is devoted to examining decentralization's impact on human resource issues from three different perspectives: that of local health managers, health workers themselves, and national health leaders. These three groups have different concerns in the human resource realm, and consequently, have been differently affected by decentralization processes. The paper concludes with recommendations regarding three key concerns that national authorities and international agencies should give prompt attention to. They are (1) defining the essential human resource policy, planning and management skills for national human resource managers who work in decentralized countries, and developing training programs to equip them with such skills; (2) supporting research that focuses on improving the knowledge base of how different modes of decentralization impact on staffing equity; and (3) identifying factors that most critically influence health worker motivation and performance under decentralization, and documenting the most cost-effective best practices to improve them. Notable experiences from South Africa, Ghana, Indonesia and Mexico are shared in an annex

Leprosy patients: neurotrophic factors and axonal markers in skin lesions

Neurotrophins are growth factors with crucial roles in neural pathophysiology. These mediators functionally modulate nociceptive fibers, and changes in neurotrophins expression have been correlated with early loss of nociception in leprosy. This study investigated the expression of NGF, BDNF, and NT3 in dermal nerves of leprosy patients. Characterization of Remak bundles was achieved by p75NTR, and axonal markers NF-L and PGP 9.5 immunostaining. Clinical parameters of neural impairment have been evaluated by Semmes-Wenstein monofilaments. Our findings demonstrated decrease of NGF in borderline leprosy, when compared to control specimens. Similar results were observed in PGP 9.5 expression (borderline: p<0.001 and lepromatous: p<0.05) and NF-L (lepromatous: p<0.05), suggesting advanced Remak bundles degeneration in multibacillary leprosy. It has also been observed positive correlation between p75NTR and PGP 9.5, indicating association between Schwann cells and axons in Remak bundles. Present data indicate that neurotrophins imbalance may participate in the establishment of peripheral nerve damage

Stochastic Competition between Mechanistically Independent Slippage and Death Pathways Determines Cell Fate during Mitotic Arrest

Variability in cell-to-cell behavior within clonal populations can be attributed to the inherent stochasticity of biochemical reactions. Most single-cell studies have examined variation in behavior due to randomness in gene transcription. Here we investigate the mechanism of cell fate choice and the origin of cell-to-cell variation during mitotic arrest, when transcription is silenced. Prolonged mitotic arrest is commonly observed in cells treated with anti-mitotic drugs. Cell fate during mitotic arrest is determined by two alternative pathways, one promoting cell death, the other promoting cyclin B1 degradation, which leads to mitotic slippage and survival. It has been unclear whether these pathways are mechanistically coupled or independent. In this study we experimentally uncoupled these two pathways using zVAD-fmk to block cell death or Cdc20 knockdown to block slippage. We then used time-lapse imaging to score the kinetics of single cells adopting the remaining fate. We also used kinetic simulation to test whether the behaviors of death versus slippage in cell populations where both pathways are active can be quantitatively recapitulated by a model that assumes stochastic competition between the pathways. Our data are well fit by a model where the two pathways are mechanistically independent, and cell fate is determined by a stochastic kinetic competition between them that results in cell-to-cell variation

Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy

<p>Abstract</p> <p>Background</p> <p><it>MyBPC3 </it>mutations are amongst the most frequent causes of hypertrophic cardiomyopathy, however, its prevalence varies between populations. They have been associated with mild and late onset disease expression. Our objectives were to establish the prevalence of <it>MyBPC3 </it>mutations and determine their associated clinical characteristics in our patients.</p> <p>Methods</p> <p>Screening by Single Strand Conformation Polymorphisms (SSCP) and sequencing of the fragments with abnormal motility of the <it>MyBPC3 </it>gene in 130 unrelated consecutive HCM index cases. Genotype-Phenotype correlation studies were done in positive families.</p> <p>Results</p> <p>16 mutations were found in 20 index cases (15%): 5 novel [D75N, V471E, Q327fs, IVS6+5G>A (homozygous), and IVS11-9G>A] and 11 previously described [A216T, R495W, R502Q (2 families), E542Q (3 families), T957S, R1022P (2 families), E1179K, K504del, K600fs, P955fs and IVS29+5G>A]. Maximum wall thickness and age at time of diagnosis were similar to patients with <it>MYH7 </it>mutations [25(7) vs. 27(8), p = 0.16], [46(16) vs. 44(19), p = 0.9].</p> <p>Conclusions</p> <p>Mutations in <it>MyBPC3 </it>are present in 15% of our hypertrophic cardiomyopathy families. Severe hypertrophy and early expression are compatible with the presence of <it>MyBPC3 </it>mutations. The genetic diagnosis not only allows avoiding clinical follow up of non carriers but it opens new possibilities that includes: to take preventive clinical decisions in mutation carriers than have not developed the disease yet, the establishment of genotype-phenotype relationship, and to establish a genetic diagnosis routine in patients with familial HCM.</p