Shared structural determinants for the calcium-independent liposome membrane permeabilization and sarcolemma depolarization in Bothropstoxin-I, a LYS49-PLA(2) from the venom of Bothrops jararacussu

The structural determinants of myotoxicity of bothropstoxin-I (BthTX-I), a Lys49 phospholipase A(2) from Bothrops jararacussu venom, were studied by measuring the resting membrane potential in the mouse phrenic nerve-diaphragm preparation. This method proved to be around 100-fold more sensitive than the creatine kinase release assay, and was used to evaluate a total of 31 site-directed BthTX-I alanine scanning mutants. Mutants that reduced the resting membrane potential were located in a surface patch defined by residues in the C-terminal loop (residues 115-129), positions 37-39 in the membrane interfacial recognition surface (Y46 and K54), and residue K93. These results expand the known structural determinants of the biological activity as evaluated by previous creatine kinase release experiments. Furthermore, a strong correlation is observed between the structural determinants of sarcolemma depolarization and calcium-independent disruption of liposome membranes, suggesting that a common mechanism of action underlies the permeabilization of the biological and model membranes. (C) 2009 Elsevier Ltd. All rights reserved.

Local delivery of EGF-liposome mediated bone modeling in orthodontic tooth movement by increasing RANKL expression

Aims: It has long been demonstrated that epidermal growth factor (EGF) has catabolic effects oil bone. Thus. we examined the role of EGF in regulating mechanically induced bone modeling in a rat model of orthodontic tooth movement. Main methods: The maxillary first molars of rats were moved mesially using an orthodontic appliance attached to the maxillary incisor teeth. Rats were randomly divided into 4 groups: (G1) administration of PBS (Phosphate buffer saline Solution (n = 24); (G2) administration of empty liposomes (it = 24): (Q) administration 20 rig of EGF Solution (n = 24): and (G4) 20 ng of EGF-liposomes Solution (it = 24). Each Solution was injected in the mucosa of the left first molar adjacent to the appliance. At days 5, 10, 14 and 2 1 after drug administration. 6 animals of each group were sacrificed. Histomorphometric analysis was used to quantify osteoclasts (Tartrate-resistant acid phosphatase (TRAP) + cells) and tooth movement. Using immunohistochemistry assay we evaluated the RANKL (receptor activator of nuclear factor kappa B ligand) and epidermal growth factor receptor (EGFR) expression. Key findings: The EGF-liposome administration showed an increased tooth movement and osteoclast numbers compared to controls (p<0.05). This was correlated with intense RANKL expression. Both osteoblasts and osteoclasts expressed EGFR. Significance: Local delivery of EGF-liposome stimulates, osteoclastogenesis and tooth movement. (C) 2009 Elsevier Inc. All rights reserved.

Brazil The Swinging Pendulum Between Labor Sociology and Labor Movement

In this article, the authors analyze the relationship between labor sociology and trade unionism in Brazil by focusing on its three key phases. Against the backdrop of successive political and economical scenarios, the authors go from the first generation of labor sociologists to the most recent period, trying to identify the transition points in this trajectory. This study develops the hypothesis that labor sociology in Brazil was first characterized by a search for affirmation and professionalization (1950-1960). Later, it developed a strong political-social engagement, and assumed a public character, by claiming particular social identities (1970-1980). Finally, it flowed toward policy sociology (1990-2000).

Relativizing Minimality for A-movement: phi- and theta-relations

This paper discusses two arguments raised against Hornstein`s (1999, 2001) Movement Theory of Control (MTC): Landau`s (2003) contrast between raising and passivized subject control predicates and Culicover and Jackendoff`s (2001) contrast between control and raising within nominals. I show that rather than counter-arguments, the data they present can actually be analyzed as arguments in favor of the MTC. More specifically, I argue that the puzzling contrasts discussed by these authors can be adequately accounted for within the MTC if minimality computations regarding A-movement are relativized in terms of phi- or theta-relations.

Social Science; black movement; racial relations; identityThe Brazilian black movement in the social sciences (1950-2000)

When and how did the Brazilian Black movement appear in the social sciences? What are the theoretical approaches and explanations for the 20th century emergence and development? This article will address these principal issues by analyzing studies that have taken on the topic of collective black mobilization from various disciplinary vantage points, particularly, Sociology, History and Anthropology.

Ventilation Patterns Influence Airway Secretion Movement

BACKGROUND: Retention of airway secretions is a common and serious problem in ventilated patients. Treating or avoiding secretion retention with mucus thinning, patient-positioning, airway suctioning, or chest or airway vibration or percussion may provide short-term benefit. METHODS: In a series of laboratory experiments with a test-lung system we examined the role of ventilator settings and lung-impedance on secretion retention and expulsion. Known quantities of a synthetic dye-stained mucus simulant with clinically relevant properties were injected into a transparent tube the diameter of an adult trachea and exposed to various mechanical-ventilation conditions. Mucus-simulant movement was measured with a photodensitometric technique and examined with image-analysis software. We tested 2 mucus-simulant viscosities and various peak flows, inspiratory/ expiratory flow ratios, intrinsic positive end-expiratory pressures, ventilation waveforms, and impedance values. RESULTS: Ventilator settings that produced flow bias had a major effect on mucus movement. Expiratory How bias associated with intrinsic positive end-expiratory pressure generated by elevated minute ventilation moved mucus toward the airway opening, whereas intrinsic positive end-expiratory pressure generated by increased airway resistance moved the mucus toward the lungs. Inter-lung transfer of mucus simulant occurred rapidly across the ""carinal divider"" between interconnected test lungs set to radically different compliances; the mucus moved out of the low-compliance lung and into the high-compliance lung. CONCLUSIONS: The movement of mucus simulant was influenced by the ventilation pattern and lung impedance. Flow bias obtained with ventilator settings may clear or embed mucus during mechanical ventilation.

DNA binding-independent transcriptional activation of the vascular endothelial growth factor gene (VEGF) by the Myb oncoprotein

Myb is a key transcription factor that can regulate proliferation, differentiation, and apoptosis, predominantly in the haemopoietic system. Abnormal expression of Myb is associated with a number of cancers, both haemopoietic and non-haemopoietic. In order to better understand the role of Myb in normal and tumorigenic processes, we undertook a cDNA array screen to identify genes that are regulated by this factor. In this way, we identified the gene encoding vascular endothelial growth factor (VEGF) as being potentially regulated by the Myb oncoprotein in myeloid cells. To determine whether this was a direct effect on VEGF gene transcription, we examined the activity of the murine VEGF promoter in the presence of either wild-type (WT) or mutant forms of Myb. It was found that WT Myb was able to activate the VEGF promoter and that a minimal promoter region of 120 bp was sufficient to confer Myb responsiveness. Surprisingly, activation of the VEGF promoter was independent of DNA binding by Myb. This was shown by the use of DNA binding-defective Myb mutants and by mutagenesis of a potential Myb-binding site in the minimal promoter. Mutation of Sp1 sites within this region abolished Myb-mediated regulation of a reporter construct, suggesting that Myb DNA binding-independent activation of VEGF expression occurs via these Sp1 binding elements. Regulation of VEGF production by Myb has implications for the potential role of Myb in myeloid leukaemias and in solid tumours where VEGF may be functioning as an autocrine growth factor. (c) 2006 Elsevier Inc. All rights reserved.

An examination of movement kinematics in young people with high-functioning autism and Asperger's disorder: Further evidence for a motor planning deficit

This paper examines upper-body movement kinematics in individuals with high-functioning autism (HFA) and Asperger's disorder (AD). In general, the results indicate that HFA is more consistently associated with impaired motoric preparation/initiation than AD. The data further suggest that this quantitative difference in motor impairment is not necessarily underpinned by greater executive dysfunction vulnerability in autism relative to AD. Quantitative motoric dissociation between autism and AD may have down-stream effects on later stages of movement resulting in qualitative differences between these disorder groups, e.g. motor clumsiness in AD versus abnormal posturing in autism. It will be important for future research to map the developmental trajectory of motor abnormalities in these disorder groups.

Viral Load Predicts New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy, Independent of CD4 T Lymphocyte Value

Background. Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. Methods. The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age ! 15 years, and continuous HAART for >= 6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. Results. The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load 15000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = 033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. Conclusions. Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.

Contraction of the abdominal muscles associated with movement of the lower limb

Background and Purpose. Activity of the trunk muscles is essential for maintaining stability of the lumbar spine because of the unstable structure of that portion of the spine. A model involving evaluation of the response of the lumbar multifidus and abdominal muscles to leg movement was developed to evaluate this function. Subjects. To examine this function in healthy persons, 9 male and 6 female subjects (mean age = 20.6 years, SD = 2.3) with no history of low back pain were studied. Methods. Fine-wire and surface electromyography electrodes were used to record the activity of selected trunk muscles and the prime movers for hip flexion, abduction, and extension during hip movements in each of these directions. Results. Trunk muscle activity occurring prior to activity of the prime mover of the limb was associated with hip movement in each direction. The transversus abdominis (TrA) muscle was invariably the first muscle that was active. Although reaction time for the TrA and oblique abdominal muscles was consistent across movement directions, reaction time for the rectus abdominis and multifidus muscles varied with the direction of limb movement. Conclusion and Discussion. Results suggest that the central nervous st stem deals with stabilization of the spine by contraction of the abdominal and multifidus muscles in anticipation of reactive forces produced by limb movement. The TrA and oblique abdominal muscles appear to contribute to a function not related to the direction of these forces.

Tenoxicam controls pain without altering orthodontic movement of maxillary canines

Arantes GM, Arantes VMN, Ashmawi HA, Posso IP To study the efficacy of tenoxicam for pain control, its potential for preemptive analgesia, and its influence on the orthodontic movement of upper canine teeth. This was a randomized controlled double-blind cross-over study. The patients were divided into three groups. Two groups received tenoxicam in daily doses of 20 mg orally for 3 days. Group A received the first dose of the drug before orthodontic activation and group B, just afterwards. Group C (control) received a placebo for 3 days. All groups had access to 750 mg of paracetamol up to four times a day. Three orthodontic activations were performed at 30-day intervals. Each patient belonged to two different groups. Pain intensity was assessed using a descriptive Pain Scale and a Visual Analog Scale. Private clinic; 36 patients undergoing bilateral canine tooth retraction. The statistical analysis did not show any difference in movement between the active groups and the control at any time. There was no statistical difference between the groups that received tenoxicam. Pain intensity in these groups was lower than in the placebo group. The difference in pain intensity between the active groups and the control was greatest at the assessment made 12 h after activation and it tended to zero, 72 h after activation. Tenoxicam did not influence orthodontic movement of the upper canines. It was effective for pain control and did not present any preemptive analgesic effect.

Evidence that two independent host genes influence the severity of tissue damage and susceptibility to acute pyelonephritis in murine systemic candidiasis

Tissue damage in the kidney and brain after systemic infection with Candida albicans was examined in recombinant inbred strains (AKXL) derived from AKR and C57/L progenitors. Nine of the 15 strains showed mild (C57/L-like) tissue damage. Of the remainder, two strains developed lesions comparable to the AKR parental strain, whereas four exhibited a much move severe pattern of tissue damage. This was characterized by pronounced mycelial growth in the brain, and gross oedema of the kidney, with extensive fungal colonization and marked tissue destruction. The presence of the null allele of the haemolytic complement gene (Hc) may be necessary but not sufficient, for the expression of the very severe lesions. The results were interpreted as reflecting the actions of two independent genes, which have been designated Carg1 and Carg2 (Candida albicans resistance genes 1 and 2). (C) 1997 Academic Press Limited.

Impairments of movement kinematics in patients with Huntington's disease: A comparison with and without a concurrent task

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movement profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand in its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its. effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.