Structural basis for metal ion coordination and the catalytic mechanism of sphingomyelinases D

Sphingomyelinases D (SMases D) from Loxosceles spider venom are the principal toxins responsible for the manifestation of dermonecrosis, intravascular hemolysis, and acute renal failure, which can result in death. These enzymes catalyze the hydrolysis of sphingomyelin, resulting in the formation of ceramide 1-phosphate and choline or the hydrolysis of lysophosphatidyl choline, generating the lipid mediator lysophosphatidic acid. This report represents the first crystal structure of a member of the sphingomyelinase D family from Loxosceles laeta (SMase I), which has been determined at 1.75-angstrom resolution using the quick cryo-soaking technique and phases obtained from a single iodine derivative and data collected from a conventional rotating anode x-ray source. SMase I folds as an (alpha/beta)(8) barrel, the interfacial and catalytic sites encompass hydrophobic loops and a negatively charged surface. Substrate binding and/or the transition state are stabilized by a Mg2+ ion, which is coordinated by Glu(32), Asp(34), Asp(91), and solvent molecules. In the proposed acid base catalytic mechanism, His(12) and His(47) play key roles and are supported by a network of hydrogen bonds between Asp(34), Asp(52), Trp(230), Asp(233), and Asn(252).

Cluster Coordination and Photoluminescence Properties of alpha-Ag2WO4 Microcrystals

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Crystal structure of a novel myotoxic Arg49 phospholipase A(2) homolog (zhaoermiatoxin) from Zhaoermia mangshanensis snake venom: Insights into Arg49 coordination and the role of Lys122 in the polarization of the C-terminus

The venom of Zhaoermia mangshanensis, encountered solely in Mt Mang in China's Hunan Province, exhibits coagulant, phosphodiesterase, L-amino acid oxidase, kallikrein, phospholipase A(2) and myotoxic activities. The catalytically inactive PLA(2) homolog referred to as zhaoermiatoxin is highly myotoxic and displays high myonecrotic and edema activities. Zhaoermiatoxin possesses a molecular weight of 13,972 Da, consists of 121 amino-acid residues crosslinked by seven disulfide bridges and shares high sequence homology with Lys49-PLA(2)s from the distantly related Asian pitvipers. However, zhaoermiatoxin possesses an arginine residue at position 49 instead of a lysine, thereby suggesting a secondary Lys49 -> Arg substitution which results in a catalytically inactive protein. We have determined the first crystal structure of zhaoermiatoxin, an Arg49-PLA(2), from Zhaoermia mangshanensis venom at 2.05 A resolution, which represents a novel member of phospholipase A(2) family. In this structure, unlike the Lys49 PLA(2)s, the C-terminus is well ordered and an unexpected non-polarized state of the putative calcium-binding loop due to the flip of Lys122 towards the bulk solvent is observed. The orientation of the Arg-49 side chain results in a similar binding mode to that observed in the Lys49 PLA(2)s; however, the guadinidium group is tri-coordinated by carbonyl oxygen atoms of the putative calcium-binding loop, whereas the N zeta atom of lysine is tetra-coordinated as a result of the different conformation adopted by the putative calcium-binding loop. (c) 2008 Elsevier Ltd. All rights reserved.

Grip and load force coordination in cyclical isometric manipulation task is not affected by the feedback type

Background: The relationship between normal and tangential force components (grip force - GF and load force - LF, respectively) acting on the digits-object interface during object manipulation reveals neural mechanisms involved in movement control. Here, we examined whether the feedback type provided to the participants during exertion of LF would influence GF-LF coordination and task performance. Methods. Sixteen young (24.7 ±3.8 years-old) volunteers isometrically exerted continuously sinusoidal FZ (vertical component of LF) by pulling a fixed instrumented handle up and relaxing under two feedback conditions: targeting and tracking. In targeting condition, FZ exertion range was determined by horizontal lines representing the upper (10 N) and lower (1 N) targets, with frequency (0.77 or 1.53 Hz) dictated by a metronome. In tracking condition, a sinusoidal template set at similar frequencies and range was presented and should be superposed by the participants' exerted FZ. Task performance was assessed by absolute errors at peaks (AEPeak) and valleys (AEValley) and GF-LF coordination by GF-LF ratios, maximum cross-correlation coefficients (r max), and time lags. Results: The results revealed no effect of feedback and no feedback by frequency interaction on any variable. AE Peak and GF-LF ratio were higher and rmax lower at 1.53 Hz than at 0.77 Hz. Conclusion: These findings indicate that the type of feedback does not influence task performance and GF-LF coordination. Therefore, we recommend the use of tracking tasks when assessing GF-LF coordination during isometric LF exertion in externally fixed instrumented handles because they are easier to understand and provide additional indices (e.g., RMSE) of voluntary force control. © 2013 Pedão et al.; licensee BioMed Central Ltd.

Permethrin chronic exposure alters motor coordination in rats: Effect of calcium supplementation and amlodipine

Recently was observed that pyrethroids decrease motor coordination and that calcium channels can be important targets for this effect. To contribute with this observation, this work studied the motor coordination and exploration (using hole-board apparatus), and locomotion (using open-field apparatus) of rats exposed to following treatments: permethrin (PM), PM plus calcium gluconate (CG) and PM plus amlodipine (AML). The results obtained show that CG or AML alone not changed the motor coordination while PM decreases it. CG kept the effect of permethrin; AML, however, decreased the values of permethrin to the control. Locomotor activity and exploration, which could confound results of motor coordination, were not modified by treatments. The concentration of PM in brain tissue was increased by the CG and AML. The neurosomatic index (weight brain/body weight) was increased by the PM and PM + CG. In conclusion, the combined results here obtained indicates that the calcium ion and the channels in which it is involved can be important targets for the toxic effect of pyrethroid insecticide permethrin on motor nerve activity of rats. (c) 2014 Elsevier B.V. All rights reserved.

Canine rabies epidemiology in Araçatuba and neighborhood, Northwestern São Paulo State - Brazil

São apresentadas algumas características epidemiológicas da raiva canina na região de Araçatuba, no período de 1993 a 1997. Dentre 1.984 cães submetidos ao diagnóstico de raiva, 351 foram positivos sendo que 89% dos casos (312/351) ocorreram na zona urbana e destes, 85% (266/312) eram de animais com proprietário. As informações sobre sexo estavam presentes em 83% das fichas e destas 61% eram de machos. A média de idade dos cães positivos foi de 34 meses. A agressividade foi um dos sintomas mais comumente observado (77%), seguido por incoordenação motora e/ou paralisia (42%) e 48% dos cães positivos haviam agredido pessoas ou outros animais. Das 182 fichas epidemiológicas que possuíam dados de vacinação, 51% (92/182) dos cães não eram vacinados. Aponta-se como possíveis razões para o aparecimento da epidemia no município de Araçatuba a baixa cobertura vacinal demonstrada pelo índice de cães não vacinados que adquiriram a doença aliado à elevada relação cão/homem (1:3,5) revelada em estudo anterior.

Structural, functional, and bioinformatics studies reveal a new snake venom homologue phospholipase A(2) class

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Postural control and automaticity in dyslexic children: The relationship between visual information and body sway

Difficulty with literacy acquisition is only one of the symptoms of developmental dyslexia. Dyslexic children also show poor motor coordination and postural control. Those problems could be associated with automaticity, i.e., difficulty in performing a task without dispending a fair amount of conscious efforts. If this is the case, dyslexic children would show difficulties in using "unperceived" sensory cues to control body sway. Therefore, the aim of the study was to examine postural control performance and the coupling between visual information and body sway in dyslexic children. Ten dyslexic children and 10 non-dyslexic children stood upright inside a moving room that remained stationary or oscillated back and forward at frequencies of 0.2 or 0.5 Hz. Body sway magnitude and the relationship between the room's movement and body sway were examined. The results indicated that dyslexic children oscillated more than non-dyslexic children in both stationary and oscillating conditions. Visual manipulation induced body sway in all children but the coupling between visual information and body sway was weaker and more variable in dyslexic children. Based upon these results, we can suggest that dyslexic children use visual information to postural control with the same underlying processes as non-dyslexic children; however, dyslexic children show poorer performance and more variability while relating visual information and motor action even in a task that does not require an active cognitive and conscious motor involvement, which may be a further evidence of automaticity problem. (C) 2011 Elsevier Ltd. All rights reserved.

Characterization and catalytic activity of 2,6-dichlorophenyl substituted iron(III) porphyrin supported on silica gel and imidazole propyl gel

In this work we have made use of the study of the interaction between Fe(TDCPP)(+) and the axial ligands OH- and imidazole in order to help characterize the heterogenized catalysts Fe(TDCPP)SG and Fe(TDCPP)IPG through UV-VIS and EPR spectroscopies and thus, better understand their different catalytic activity in the oxidation of cyclohexane by PhIO. We have found out that in Fe(TDCPP)SG (containing 1.2 X 10(-6) mol Fe(TDCPP)(+)/g of support), the FeP bis-coordinates to silica gel through Fe-O coordination and it is high-spin (FeP)-P-III species. In Fe(TDCPP)IPG 1 (containing 1.1 X 10(-6) mol Fe(TDCPP)(+) and 2.2 X 10(-4) mol imidazole/g of support), the FeP is bis-ligated to imidazole propyl gel through Fe-imidazole coordination and using NO as a paramagnetic probe, we present evidence that Fe(TDCPP)(+) is present as a mixture of low-spin (FeP)-P-III and (FeP)-P-II species. This catalyst led to a relative low yield of cyclohexanol (25%) because the bis-coordination of the (FeP)-P-III to the support partially blocks the reaction between Fe(TDCPP)(+) and PhIO, thus leading to the formation of only a small amount of the active species Fe-IV(OP+, while the (FeP)-P-II species do not react with the oxygen donor. Increasing the amount of Fe(TDCPP)(+) and decreasing the amount of imidazole in the support led to the obtention of high-spin (FeP)-P-III EPR signals in the spectra of Fe(TDCPP)IPG 5 (containing 4.4 X 10(-6) mol Fe(TDCPP)(+) and 2.2 X 10(-5) mol imidazole/g of IPG), together with low-spin (FeP)-P-III species. This latter catalyst led to better cyclohexanol yields (67%) than Fe(TDCPP)IPG 1. Fe(TDCPP)IPG 5 was further used in a study of the optimization of its catalytic activity and in recycling experiments in the optimized conditions. Recycling oxidation reactions of Fe(TDCPP)IPG 5 led to a total turnover number of 201 and total cyclohexanol yield of 201%, which could not be attained with Fe(TDCPP)Cl in homogeneous solution (turnover = 96) due to the difficulty in recovering and reusing it.

Exercise programs improve mobility and balance in people with Parkinson's disease

Compromised balance and loss of mobility are among the major consequences of Parkinson's disease (PD). The literature documents numerous effective interventions for improving balance and mobility. The purpose of this study was to verify the effectiveness of two exercise programs on balance and mobility in people with idiopathic PD. Thirty-four participants, with idiopathic PD that ranged from Stage I to Stage III on the Hoehn & Yahr (H&Y) scale, were assigned to two groups. Group 1 (n = 21; 67±9 years old) was engaged in an intensive exercise program (aerobic capacity, flexibility, strength, motor coordination and balance) for 6 months: 72 sessions, 3 times a week, 60 minutes per session; while Group 2 (n = 13; 69±8 years old) participated in an adaptive program (flexibility, strength, motor coordination and balance) for 6 months: 24 sessions, once a week, 60 minutes per session. Balance and basic functional mobility were assessed in pre- and post-tests by means of the Berg Balance Scale and the Timed Up and Go Test. Before and after the interventions, groups were similar in clinical conditions (H&Y, UPDRS, and Mini-Mental). A MANOVA 2 (programs) by 2 (moments) revealed that both groups were affected by the exercise intervention. Univariate analyses showed that participants improved their mobility and balance from pre- to post-test. There were no differences between groups in either mobility or balance results. Both the intensive and adaptive exercise programs improved balance and mobility in patients with PD. © 2009 Elsevier Ltd. All rights reserved.

Efficacy of a perceptual and visual-motor skill intervention program for students with dyslexia

Purpose: To verify the efficacy of a perceptual and visual-motor skill intervention program for students with dyslexia. Methods: The participants were 20 students from third to fifth grade of a public elementary school in Marília, São Paulo, aged from 8 years to 11 years and 11 months, distributed into the following groups: Group I (GI; 10 students with developmental dyslexia) and Group II (GII; 10 students with good academic performance). A perceptual and visual-motor intervention program was applied, which comprised exercises for visual-motor coordination, visual discrimination, visual memory, visual-spatial relationship, shape constancy, sequential memory, visual figure-ground coordination, and visual closure. In pre- and post-testing situations, both groups were submitted to the Test of Visual-Perceptual Skills (TVPS-3), and the quality of handwriting was analyzed using the Dysgraphia Scale. Results: The analyzed statistical results showed that both groups of students had dysgraphia in pretesting situation. In visual perceptual skills, GI presented a lower performance compared to GII, as well as in the quality of writing. After undergoing the intervention program, GI increased the average of correct answers in TVPS-3 and improved the quality of handwriting. Conclusion: The developed intervention program proved appropriate for being applied to students with dyslexia, and showed positive effects because it provided improved visual perception skills and quality of writing for students with developmental dyslexia.

Fingerprints of short-range and long-range structure in BaZr1-xHfxO3 solid solutions: an experimental and theoretical study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of a multimodal exercise program on the functional capacity of Parkinson's disease patients considering disease severity and gender

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Denoising swallowing sound to improve the evaluator's qualitative analysis

Swallowing dynamics involves the coordination and interaction of several muscles and nerves which allow correct food transport from mouth to stomach without laryngotracheal penetration or aspiration. Clinical swallowing assessment depends on the evaluator's knowledge of anatomic structures and of neurophysiological processes involved in swallowing. Any alteration in those steps is denominated oropharyngeal dysphagia, which may have many causes, such as neurological or mechanical disorders. Videofluoroscopy of swallowing is presently considered to be the best exam to objectively assess the dynamics of swallowing, but the exam needs to be conducted under certain restrictions, due to patient's exposure to radiation, which limits periodical repetition for monitoring swallowing therapy. Another method, called cervical auscultation, is a promising new diagnostic tool for the assessment of swallowing disorders. The potential to diagnose dysphagia in a noninvasive manner by assessing the sounds of swallowing is a highly attractive option for the dysphagia clinician. Even so, the captured sound has an amount of noise, which can hamper the evaluator's decision. In that way, the present paper proposes the use of a filter to improve the quality of audible sound and facilitate the perception of examination. The wavelet denoising approach is used to decompose the noisy signal. The signal to noise ratio was evaluated to demonstrate the quantitative results of the proposed methodology. (C) 2007 Elsevier Ltd. All rights reserved.

The origin of photoluminescence in amorphous lead titanate

We discuss the nature of visible photoluminescence at room temperature in amorphous lead titanate in the light of the results of recent experimental and theoretical calculations. Experimental results obtained by XANES and EXAFS revealed that amorphous lead titanate is composed of a Ti-O network having fivefold Ti coordination and NBO-type (non-bridging oxygen) defects. These defects can modify the electronic structure of amorphous compounds. Our calculation of the electronic structure involved the use of first-principle molecular calculations to simulate the variation of the electronic structure in the lead titanate crystalline phase, which is known to have a direct band gap, and we also made an in-depth examination of amorphous lead titanate. The results of our theoretical calculations of amorphous lead titanate indicate that the formation of fivefold coordination in the amorphous system may introduce delocalized electronic levels in the HOMO ( highest occupied molecular orbital) and the LUMO ( lowest unoccupied molecular orbital). A comparison of the experimental and theoretical results of amorphous compounds suggests the possibility of a radiative recombination (electron-hole pairs), which may be responsible for the emission of photoluminescence. (C) 2003 Kluwer Academic Publishers.