Structural Aspects of the Distinct Biochemical Properties of Glutaredoxin 1 and Glutaredoxin 2 from Saccharomyces cerevisiae

Glutaredoxins (Grxs) are small (9-12 kDa) heat-stable proteins that are ubiquitously distributed. In Saccharomyces cerevisiae, seven Grx enzymes have been identified. Two of them (yGrx1 and yGrx2) are dithiolic, possessing a conserved Cys-Pro-Tyr-Cys motif. Here, we show that yGrx2 has a specific activity 15 times higher than that of yGrx1, although these two oxidoreductases share 64% identity and 85% similarity with respect to their amino acid sequences. Further characterization of the enzymatic activities through two-substrate kinetics analysis revealed that yGrx2 possesses a lower Km for glutathione and a higher turnover than yGrx1. To better comprehend these biochemical differences, the pK(a) of the N-terminal active-site cysteines (Cys27) of these two proteins and of the yGrx2-C30S mutant were determined. Since the pK(a) values of the yGrx1 and yGix2 Cys27 residues are very similar, these parameters cannot account for the difference observed between their specific activities. Therefore, crystal structures of yGrx2 in the oxidized form and with a glutathionyl mixed disulfide were determined at resolutions of 2.05 and 1.91 angstrom, respectively. Comparisons of yGrx2 structures with the recently determined structures of yGrx1 provided insights into their remarkable functional divergence. We hypothesize that the substitutions of Ser23 and Gln52 in yGrx1 by Ala23 and Glu52 in yGrx2 modify the capability of the active-site C-terminal cysteine to attack the mixed disulfide between the N-terminal active-site cysteine and the glutathione molecule. Mutagenesis studies supported this hypothesis. The observed structural and functional differences between yGrx1 and yGrx2 may reflect variations in substrate specificity. (C) 2008 Elsevier Ltd. All rights reserved.

Different Aspects of General Anesthesia in Pediatric Dentistry: A Review

Context:Most child population is able to undergo dental treatment in the conventional setting. However, some children fail to cope with in-office conscious state and cannot respond to usual management modalities. This review aims to discuss the topic further. Evidence Acquisition: A computerized search in databases PubMed, MEDLINE, EMBASE, Google Scholar and Google were performed using dental general anesthesia related keywords. Original and review English-written articles that were limited to child population were retrieved without any limitation of publication date. The suitable papers were selected and carefully studied. A data form designed by author was used to write relevant findings. Results: Preoperative oral examination and comprehensive evaluation of treatment needs is only possible after clinical and radiographic oral examination. Effective collaboration in dental GA team should be made to minimize psychological trauma of children who undergo dental GA. Before conducting comprehensive dental treatment under GA, the general health of the child and the success rate of procedures provided needs to be accurately evaluated. It is noteworthy that determination of the optimal timing for GA dental operation is of great importance. Providing safety with pediatric dental rehabilitation under GA is critical. Conclusions: Besides criteria for case selection of dental GA, some degree of dental practitioner’s judgment is required to make decision. Pre- and post-operative instructions to parents or caregiver decrease the risk of complications. However, trained resuscitation providers, careful monitoring and advanced equipment minimize adverse outcomes.

Understanding the Impact of the Property Tax Appeal Process on Assessment Uniformity: Procedures, Structures, and Outcomes

Property taxes serve as a vital revenue source for local governments. The revenues derived from the property tax function as the primary funding source for a variety of critical local public service systems. Property tax appeal systems serve as quasi-administrative-judicial mechanisms intended to assure the public that property tax assessments are correct, fair, and equitable. Despite these important functions, there is a paucity of empirical research related to property tax appeal systems. This study contributes to property tax literature by identifying who participates in the property tax appeal process and examining their motivations for participation. In addition, the study sought to determine whether patterns of use and success in appeal systems affected the distribution of the tax burden. Data were collected by means of a survey distributed to single-family property owners from two Florida counties. In addition, state and county documents were analyzed to determine appeal patterns and examine the impact on assessment uniformity, over a three-year period. The survey data provided contextual evidence that single-family property owners are not as troubled by property taxes as they are by the conduct of local government officials. The analyses of the decision to appeal indicated that more expensive properties and properties excluded from initial uniformity analyses were more likely to be appealed, while properties with homestead exemptions were less likely to be appealed. The value change analyses indicated that appeals are clustered in certain geographical areas; however, these areas do not always experience a greater percentage of the value changes. Interestingly, professional representation did not increase the probability of obtaining a reduction in value. Other relationships between the variables were discovered, but often with weak predictive ability. Findings from the assessment uniformity analyses were also interesting. The results indicated that the appeals mechanisms in both counties improved assessment uniformity. On average, appealed properties exhibited greater horizontal and vertical inequities, as compared to non-appealed properties, prior to the appeals process. After, the appeal process was completed; the indicators of horizontal and vertical equity were largely improved. However, there were some indications of regressivity in the final year of the study.

Using health-related quality of life instruments for children with long-term conditions : On the basis of a national quality registry system

Introduction: There has been a continuous development of new technologies in healthcare that are derived from national quality registries. However, this innovation needs to be translated into the workflow of healthcare delivery, to enable children with long-term conditions to get the best support possible to manage their health during everyday life. Since children living with long-term conditions experience different interference levels in their lives, healthcare professionals need to assess the impact of care on children’s day-to-day lives, as a complement to biomedical assessments. Aim: The overall aim of this thesis was to explore and describe the use of instruments about health-related quality of life (HRQOL) in outpatient care for children with long-term conditions on the basis of a national quality registry system. Methods: The research was conducted by using comparative, cross-sectional and explorative designs and data collection was performed by using different methods. The questionnaire DISABKIDS Chronic Generic Measure -37 was used as well as semi-structured interviews and video-recordings from consultations. Altogether, 156 children (8–18 years) and nine healthcare professionals participated in the studies. Children with Type 1 Diabetes (T1D) (n 131) answered the questionnaire DISABKIDS and children with rheumatic diseases, kidney diseases and T1D (n 25) were interviewed after their consultation at the outpatient clinic after the web-DISABKIDS had been used. In total, nine healthcare professionals used the HRQOL instrument as an assessment tool during the encounters which was video-recorded (n 21). Quantitative deductive content analysis was used to describe content in different HRQOL instruments. Statistical inference was used to analyse results from DISABKIDS and qualitative content analysis was used to analyse the interviews and video-recordings. Results: The findings showed that based on a biopsychosocial perspective, both generic and disease-specific instruments should be used to gain a comprehensive evaluation of the child’s HRQOL. The DISABKIDS instrument is applicable when describing different aspects of health concerning children with T1D. When DISABKIDS was used in the encounters, children expressed positive experiences about sharing their results with the healthcare professional. It was discovered that different approaches led to different outcomes for the child when the healthcare professionals were using DISABKIDS during the encounter. When an instructing approach is used, the child’s ability to learn more about their health and how to improve their health is limited. When an inviting or engaging approach is used by the professional, the child may become more involved during the conversations. Conclusions: It could be argued that instruments of HRQOL could be used as a complement to biomedical variables, to promote a biopsychosocial perspective on the child’s health. According to the children in this thesis, feedback on their results after answering to web-DISABKIDS is important, which implies that healthcare professionals need to prioritize time for discussions about results from HRQOL instruments in the encounters. If healthcare professionals involve the child in the discussion of the results of the HRQOL, misinterpreted answers could be corrected during the conversation. Concurrently, this claims that healthcare professionals invite and engage the child.

Reproductive aspects of the undulate ray, Raja undulata, from the south coast of Portugal

The maturity of the undulate ray, Raja undulata, one of the most important by-catch elasmobranch species captured in south Portugal, was studied for the first time. Females ranged in total length (TL) from 19.4 to 88.2 cm and males from 23.0 to 83.2 cm. The gonadosomatic index for females was higher during the winter, meaning that this species reproduces during this season. Females matured at significantly larger sizes and older ages than males, with 50% of the females mature at 76.2 cm TL at an age of 8.98 years while 50% maturity for males was achieved at 73.6 cm TL and 7.66 years. Females were mature at 86.3% of the maximum observed size and 69.1% of the maximum observed age while males matured at 88.5% of the maximum observed size and 63.8% of the maximum observed age, making this a very late maturing species, with important consequences in terms of fisheries management and conservation. (c) 2006 Elsevier B.V. All rights reserved.

Evolution and challenges of dynamic global vegetation models for some aspects of plant physiology and elevated atmospheric CO2.

Dynamic global vegetation models (DGVMs) simulate surface processes such as the transfer of energy, water, CO2, and momentum between the terrestrial surface and the atmosphere, biogeochemical cycles, carbon assimilation by vegetation, phenology, and land use change in scenarios of varying atmospheric CO2 concentrations. DGVMs increase the complexity and the Earth system representation when they are coupled with atmospheric global circulation models (AGCMs) or climate models. However, plant physiological processes are still a major source of uncertainty in DGVMs. The maximum velocity of carboxylation (Vcmax), for example, has a direct impact over productivity in the models. This parameter is often underestimated or imprecisely defined for the various plant functional types (PFTs) and ecosystems. Vcmax is directly related to photosynthesis acclimation (loss of response to elevated CO2), a widely known phenomenon that usually occurs when plants are subjected to elevated atmospheric CO2 and might affect productivity estimation in DGVMs. Despite this, current models have improved substantially, compared to earlier models which had a rudimentary and very simple representation of vegetation?atmosphere interactions. In this paper, we describe this evolution through generations of models and the main events that contributed to their improvements until the current state-of-the-art class of models. Also, we describe some main challenges for further improvements to DGVMs.

Statistical Analysis and Modelling Aspects of Thermally Driven Turbulence

The present work aims to provide a deeper understanding of thermally driven turbulence and to address some modelling aspects related to the physics of the flow. For this purpose, two idealized systems are investigated by Direct Numerical Simulation: the rotating and non-rotating Rayleigh-Bénard convection. The preliminary study of the flow topologies shows how the coherent structures organise into different patterns depending on the rotation rate. From a statistical perspective, the analysis of the turbulent kinetic energy and temperature variance budgets allows to identify the flow regions where the production, the transport, and the dissipation of turbulent fluctuations occur. To provide a multi-scale description of the flows, a theoretical framework based on the Kolmogorov and Yaglom equations is applied for the first time to the Rayleigh-Bénard convection. The analysis shows how the spatial inhomogeneity modulates the dynamics at different scales and wall-distances. Inside the core of the flow, the space of scales can be divided into an inhomogeneity-dominated range at large scales, an inertial-like range at intermediate scales and a dissipative range at small scales. This classic scenario breaks close to the walls, where the inhomogeneous mechanisms and the viscous/diffusive processes are important at every scale and entail more complex dynamics. The same theoretical framework is extended to the filtered velocity and temperature fields of non-rotating Rayleigh-Bénard convection. The analysis of the filtered Kolmogorov and Yaglom equations reveals the influence of the residual scales on the filtered dynamics both in physical and scale space, highlighting the effect of the relative position between the filter length and the crossover that separates the inhomogeneity-dominated range from the quasi-homogeneous range. The assessment of the filtered and residual physics results to be instrumental for the correct use of the existing Large-Eddy Simulation models and for the development of new ones.

Neurophysiological, molecular and pathophysiological aspects of synthetic torpor

Synthetic torpor is a peculiar physiological condition resembling natural torpor, in which even non-hibernating species can be induced through different pharmacological approaches. The growing interest in the induction of a safe synthetic torpor state in non-hibernating species stems from the possible applications that it may have in a translational perspective. In particular, the deeper understanding of the functional changes occurring during and after synthetic torpor may lead to the standardization of a safe procedure to be used also in humans and to the implementation of new therapeutic strategies. Some of the most interesting and peculiar characteristics of torpor that should be assessed in synthetic torpor and may have a translational relevance are: the reversible hyperphosphorylation of neuronal Tau protein, the strong and extended neural plasticity, which may be related to Tau regulatory processes, and the development of radioresistance. In this respect, in the present thesis, rats were induced into synthetic torpor by the pharmacological inhibition of the raphe pallidus, a key brainstem thermoregulatory area, in order to assess: i) whether a reversible hyperphosphorylation of Tau protein occurs at the spinal cord level, also testing the possible involvement of microglia activation in this phenomenon; ii) sleep quality after synthetic torpor and its possible involvement in the process of Tau dephosphorylation; iii) whether synthetic torpor has radioprotective properties, by assessing histopathological and molecular features in animals exposed to X-rays irradiation. The results showed that: i) a reversible hyper-phosphorylation of Tau protein also occurs in synthetic torpor in the dorsal horns of the spinal cord; ii) sleep regulation after synthetic torpor seems to be physiological, and sleep deprivation speeds up Tau dephosphorylation; iii) synthetic torpor induces a consistent increase in radioresistance, as shown by analyses at both histological and molecular level.

Non perturbative aspects of non equilibrium physics in two dimensional models

The present manuscript focuses on out of equilibrium physics in two dimensional models. It has the purpose of presenting some results obtained as part of out of equilibrium dynamics in its non perturbative aspects. This can be understood in two different ways: the former is related to integrability, which is non perturbative by nature; the latter is related to emergence of phenomena in the out of equilibirum dynamics of non integrable models that are not accessible by standard perturbative techniques. In the study of out of equilibirum dynamics, two different protocols are used througout this work: the bipartitioning protocol, within the Generalised Hydrodynamics (GHD) framework, and the quantum quench protocol. With GHD machinery we study the Staircase Model, highlighting how the hydrodynamic picture sheds new light into the physics of Integrable Quantum Field Theories; with quench protocols we analyse different setups where a non-perturbative description is needed and various dynamical phenomena emerge, such as the manifistation of a dynamical Gibbs effect, confinement and the emergence of Bloch oscillations preventing thermalisation.

Bisphosphonate-related Osteonecrosis Of The Jaw: A Review Of The Literature.

Bisphosphonates (BPs) are a class of drugs used to treat osteoporosis and malignant bone metastasis. BPs show high binding capacity to the bone matrix, especially in sites of active bone metabolism. The American Society for Bone and Mineral Research defines BRONJ as an area of exposed bone in the maxillofacial region that has not healed within 8 weeks after identification by a healthcare provider in a patient who is receiving or has been exposed to a bisphosphonate and has not had radiation therapy to the craniofacial region. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) can adversely affect quality of life, as it may produce significant morbidity. The American Association of Oral and Maxillofacial Surgeons (AAOMS) considers as vitally important that information on BRONJ be disseminated to other dental and medical specialties. The purpose of this work is to offer a perspective on how dentists should manage patients on BPs, to show the benefits of accurately diagnosing BRONJ, and to present diagnostic aids and treatments strategies for the condition.

Genetic Aspects Of Athletic Performance: The African Runners Phenomenon.

The current dominance of African runners in long-distance running is an intriguing phenomenon that highlights the close relationship between genetics and physical performance. Many factors in the interesting interaction between genotype and phenotype (eg, high cardiorespiratory fitness, higher hemoglobin concentration, good metabolic efficiency, muscle fiber composition, enzyme profile, diet, altitude training, and psychological aspects) have been proposed in the attempt to explain the extraordinary success of these runners. Increasing evidence shows that genetics may be a determining factor in physical and athletic performance. But, could this also be true for African long-distance runners? Based on this question, this brief review proposed the role of genetic factors (mitochondrial deoxyribonucleic acid, the Y chromosome, and the angiotensin-converting enzyme and the alpha-actinin-3 genes) in the amazing athletic performance observed in African runners, especially the Kenyans and Ethiopians, despite their environmental constraints.

Brij Detergents Reveal New Aspects Of Membrane Microdomain In Erythrocytes.

Membrane microdomains enriched in cholesterol, sphingolipids (rafts), and specific proteins are involved in important physiological functions. However their structure, size and stability are still controversial. Given that detergent-resistant membranes (DRMs) are in the liquid-ordered state and are rich in raft-like components, they might correspond to rafts at least to some extent. Here we monitor the lateral order of biological membranes by characterizing DRMs from erythrocytes obtained with Brij-98, Brij-58, and TX-100 at 4 °C and 37 °C. All DRMs were enriched in cholesterol and contained the raft markers flotillin-2 and stomatin. However, sphingomyelin (SM) was only found to be enriched in TX-100-DRMs - a detergent that preferentially solubilizes the membrane inner leaflet - while Band 3 was present solely in Brij-DRMs. Electron paramagnetic resonance spectra showed that the acyl chain packing of Brij-DRMs was lower than TX-100-DRMs, providing evidence of their diverse lipid composition. Fatty acid analysis revealed that the SM fraction of the DRMs was enriched in lignoceric acid, which should specifically contribute to the resistance of SM to detergents. These results indicate that lipids from the outer leaflet, particularly SM, are essential for the formation of the liquid-ordered phase of DRMs. At last, the differential solubilization process induced by Brij-98 and TX-100 was monitored using giant unilamellar vesicles. This study suggests that Brij and TX-100-DRMs reflect different degrees of lateral order of the membrane microdomains. Additionally, Brij DRMs are composed by both inner and outer leaflet components, making them more physiologically relevant than TX-100-DRMs to the studies of membrane rafts.

Transcutaneous Tibial Nerve Stimulation In The Treatment Of Lower Urinary Tract Symptoms And Its Impact On Health-related Quality Of Life In Patients With Parkinson Disease: A Randomized Controlled Trial.

A randomized controlled trial study was performed to evaluate the efficacy of transcutaneous tibial nerve stimulation (TTNS) and sham TTNS, in patients with Parkinson disease (PD) with lower urinary tract symptoms (LUTS). Randomized controlled trial. Thirteen patients with a diagnosis of PD and bothersome LUTS were randomly allocated to one of the following groups: Group I: TTNS group (n = 8) and group II: Sham group (n = 5). Both groups attended twice a week during 5 weeks; each session lasted 30 minutes. Eight patients received TTNS treatment and 5 subjects allocated to group II were managed with sham surface electrodes that delivered no electrical stimulation. Assessments were performed before and after the treatment; they included a 3-day bladder diary, Overactive Bladder Questionnaire (OAB-V8), and the International Consultation on Incontinence Quality of Life Questionnaire Short Form (ICIQ-SF), and urodynamic evaluation. Following 5 weeks of treatment, patients allocated to TTNS demonstrated statistically significant reductions in the number of urgency episodes (P = .004) and reductions in nocturia episodes (P < .01). Participants allocated to active treatment also showed better results after treatment in the OAB-V8 and ICIQ-SF scores (P < .01, respectively). Urodynamic testing revealed that patients in the active treatment group showed improvements in intravesical volume at strong desire to void (P < .05) and volume at urgency (P < .01) when compared to subjects in the sham treatment group. These findings suggest that TTNS is effective in the treatment of LUTS in patients with PD, reducing urgency and nocturia episodes and improving urodynamic parameters as well as symptom scores measured by the OAB-V8 and health-related quality-of-life scores measured by the ICIQ-SF.

Structural aspects of the p.P222Q homozygous mutation of HSD3B2 gene in a patient with congenital adrenal hyperplasia

Type II 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD2), encoded by the HSD3B2 gene, is a key enzyme involved in the biosynthesis of all the classes of steroid hormones. Deleterious mutations in the HSD3B2 gene cause the classical deficiency of 3β-HSD2, which is a rare autosomal recessive disease that leads to congenital adrenal hyperplasia (CAH). CAH is the most frequent cause of ambiguous genitalia and adrenal insufficiency in newborn infants with variable degrees of salt losing. Here we report the molecular and structural analysis of the HSD3B2 gene in a 46,XY child, who was born from consanguineous parents, and presented with ambiguous genitalia and salt losing. The patient carries a homozygous nucleotide c.665C>A change in exon 4 that putatively substitutes the proline at codon 222 for glutamine. Molecular homology modeling of normal and mutant 3β-HSD2 enzymes emphasizes codon 222 as an important residue for the folding pattern of the enzyme and validates a suitable model for analysis of new mutations.

Aspectos motores da Paralisia Cerebral Espástica diparética : o Nintendo WII 'MARCA REGISTRADA' como atividade motora complementar = Motor aspects of Spastic Cerebral Palsy : the Nintendo WII 'TRADEMARK' as a supplementary motor activity

Universidade Estadual de Campinas . Faculdade de Educação Física