Structure of acetone and dimethyl sulfoxide from Monte Carlo simulations and MM2 calculations

The structure of acetone and dimethyl sulfoxide in the liquid phase is investigated using Monte Carlo simulations and MM2 calculations. The principal site - site correlations and degree of structure in both liquids have been investigated. The results showed that dimethyl sulfoxide is more structured than acetone. At short distances the dipoles of neighboring molecules are found to be in antiparallel configurations, but further apart the molecules tend to be aligned predominantly as head to tail. In both liquids there is evidence of strong methyl - oxygen interaction, important to the structure of the liquids. The contacts suggest weak hydrogen bonds between methyl hydrogen and oxygen.

Envenomation by a benthic Hydrozoa (Cnidaria): the case of Nemalecium lighti (Haleciidae)

A case of envenomation caused by the Nemalecium lighti is described. The hydrozoan species lives in many kinds of substrates, being quite common in tropical shallow water. The patient, a marine biologist, had contact with the animal in two different opportunities while snorkeling. Both contacts produced erythematous and highly pruriginous papules in exposed areas of the body. The signs and symptoms persisted for a week and healed without sequellae. (C) 2001 Elsevier B.V. Ltd. All rights reserved.

Injuries caused by scorpionfishes and (Scorpaena plumieri Bloch, 1789 Scorpaena brasiliensis Cuvier 1829) in the Southwestern Atlantic Ocean (Brazilian coast): epidemiologic, clinic and therapeutic aspects of 23 stings in humans

Fishes of the family Scorpaenidae are responsible for severe injuries and occasionally deaths in humans around the world. The more venomous fishes on the Brazilian coast and in the Southwestern Atlantic region are classified in the genus Scorpaena (family Scorpaenidae). However, there are few studies on the venomous apparatus, the effects of the venom, or clinical aspects of human envenoming provoked by Atlantic scorpionfishes.In this communication, the authors present 23 accidents caused by scorpionfishes of the genus Scorpaena among fishermen, and report the species that provoked the injuries, the circumstances of contacts, the clinical aspects observed and the therapeutic measures utilized for control of the symptoms of the victims. The intense pain and the systemic findings observed in the patients were very frequent and we think that the injuries provoked by scorpionfishes should be considered the most important manifestations caused by venomous fishes of the East Atlantic Ocean. (C) 2003 Elsevier B.V. Ltd. All rights reserved.

Armadillo meat intake was not associated with leprosy in a case control study, Curitiba (Brazil)

Leprosy's progression and its maintained endemic status, despite the availability of effective treatments, are not fully understood and recent studies have highlighted the possibility of involved Mycobacterium leprae ambient reservoirs. Wild armadillos can carry leprosy and, because their meat is eaten by humans, development of the disease among armadillo meat consumers has been investigated. This study evaluated the frequency of armadillo meat intake among leprosy patients as well as age and gender matched controls with other skin diseases from a dermatological unit. Armadillo meat consumption among both groups was adjusted by demographic and socioeconomic covariates based on a conditional multiple logistic regression model. One hundred twenty-one cases and 242 controls were evaluated; they differed in socioeconomic variables such as family income, hometown population and access to treated water. The multivariate analysis did not show an association between the intake of armadillo meat and leprosy (odds ratio = 1.07; CI 95% 0.56-2.04), even when only cases with no known contacts were analyzed. We conclude that leprosy is not associated with the intake of armadillo meat in these patients.

Sorologia Anti PGL-1 e risco de ocorrência de hanseníase em área de alta endemicidade do Estado de São Paulo: quatro anos de seguimento

Os testes sorológicos para diagnóstico de hanseníase, usando o glicolipídeo-fenólico-1 (PGL-1), considerado antígeno específico do M. leprae, têm aberto algumas possibilidades de estudo do comportamento epidemiológico desta doença. Algumas questões, como tempo de latência da doença, infecção subclínica e importância do contato intra-domiciliar (contatos) no controle da endemia, puderam ser melhor analisadas usando este instrumental. Este estudo teve por objetivo verificar a existência de associação entre a situação sorológica e a ocorrência de hanseníase. Foram seguidas, durante 4 anos, 6.520 pessoas com idade igual ou superior a 5 anos, submetidas no início do seguimento ao teste sorológico Anti PGL-1, pertencentes ao universo de 7.416 habitantes da área urbana de um município paulista caracterizado por elevada endemicidade de hanseníase. Foi identificado um grupo de 590 indivíduos soropositivos (9,0 %). Foram diagnosticados, no período, 82 casos novos de hanseníase, 26 no grupo de soropositivos (441 casos novos/10.000 indivíduos) e 48 no de soronegativos (81/10.000). Entre os que não fizeram sorologia, surgiram 8 casos novos (89/10.000). Procurou-se controlar, na análise, a condição de contato, dado que a taxa de soropositividade padronizada por idade e sexo era de 9,61% no grupo de contatos e 7,65% no de não-contatos. Tomando-se os não-contatos soronegativos como o grupo de não expostos, foram calculados os riscos relativos de adoecimento no período, a partir das taxas de detecção padronizadas por idade, resultando no seguinte: os contatos ID soropositivos apresentaram a taxa de 1.704/10.000, 27 vezes maior que a dos não-expostos, igual a 63/10.000; os não-contatos soropositivos e os contatos soronegativos apresentaram taxas, respectivamente, de 274 e 198/10.000, ambas maiores que as dos não-expostos e iguais entre si. A soropositividade associou-se à elevação de 8,6 vezes do risco de hanseníase entre os contatos e de 4,4 entre os não-contatos. Na situação epidemiológica estudada, caracterizada por elevada endemicidade de hanseníase, 50% dos casos novos surgiram entre os não-contatos soronegativos, ou seja, sem fonte de infecção conhecida. Portanto, o teste anti-PGL-1 usado revela-se, na prática, de pouca aplicabilidade. Resta estudar ainda o comportamento da sorologia anti-PGL-1 em áreas de média e baixa endemicidade para que se possa tirar conclusões mais consubstanciadas sobre sua utilidade no controle da endemia. Recomenda-se o aprofundamento das pesquisas sorológicas e de outras que aprimorem o diagnóstico precoce da infecção subclínica, inclusive para detecção de formas paucibacilares, para se ampliar as possibilidades de influir no controle endêmico.

Alternative pathways for catecholamine action in oral motor control

Orofacial movement is a complex function performed by facial and jaw muscles. Jaw movement is enacted through the triggering of motoneurons located primarily in the trigeminal motor nucleus (Mo5). The Mo5 is located in the pontine reticular formation, which is encircled by premotor neurons. Previous studies using retrograde tracers have demonstrated that premotor neurons innervating the Mo5 are distributed in brainstem areas, and electrophysiological studies have suggested the existence of a subcortical relay in the corticofugal-Mo5 pathway. Various neurotransmitters have been implicated in oral movement. Dopamine is of special interest since its imbalance may produce changes in basal ganglia activity, which generates abnormal movements, including jaw motor dysfunction, as in oral dyskinesia and possibly in bruxism. However, the anatomical pathways connecting the dopaminergic systems with Mo5 motoneurons have not been studied systematically. After injecting retrograde tracer fluorogold into the Mo5, we observed retrograde-labeled neurons in brainstem areas and in a few forebrain nuclei, such as the central nucleus of the amygdala, and the parasubthalamic nucleus. By using dual-labeled immunohistochemistry, we found tyrosine hydroxylase (a catecholamine-processing enzyme) immunoreactive fibers in close apposition to retrograde-labeled neurons in brainstem nuclei, in the central nucleus of the amygdala and the parasubthalamic nucleus, suggesting the occurrence of synaptic contacts. Therefore, we suggested that catecholamines may regulate oralfacial movements through the premotor brainstem nuclei, which are related to masticatory control, and forebrain areas related to autonomic and stress responses. (C) 2005 Elsevier B.V.. All rights reserved.

CLINICAL EVALUATION of THE ASSOCIATION BETWEEN NONCARIOUS CERVICAL LESIONS and OCCLUSAL FORCES

Statement of problem. Noncarious cervical lesions (NCCLs) are a frequent challenge in clinical dental practice, given the variety of opinions regarding their etiology, diagnosis, and treatment.Purpose. The purpose of this study was to assess the potential relationship between occlusal forces and the occurrence of NCCLs.Material and methods. The participant population consisted of 111 volunteers (30 male and 81 female, mean age 23.6 years). General personal information was recorded, after which participants were examined for the presence and location of NCCLs, gingival recession, fracture lines, dental and restoration fractures, presence and location of tooth wear, type of occlusal guidance scheme for lateral mandibular movements, and existence of occlusal interference or premature contacts. The participants were divided according to the presence or absence of NCCLs, and data were statistically analyzed with the Independent t test, the Chi-square test, and the Fisher exact test (alpha=.05).Results. A significant association was found between the presence of NCCLs and age (P=.008), gingival recession (P<.001), occlusal trauma (P<.001), presence (P<.001) and location of tooth wear, and group function as occlusal guidance scheme in lateral excursive movements (P<.001).Conclusions. A strong relationship between the presence of NCCLs and occlusal overload was found. (J Prosthet Dent 2012;108:298-303)

Comparative evaluation of the efficacy of occlusal splints fabricated in centric relation or maximum intercuspation in temporomandibular disorders patients

Fabrication of occlusal splints in centric relation for temporomandibular disorders (TMD) patients is arguable, since this position has been defined for asymptomatic stomatognathic system. Thus, maximum intercuspation might be employed in patients with occlusal stability, eliminating the need for interocclusal records. This study compared occlusal splints fabricated in centric relation and maximum intercuspation in muscle pain reduction of TMD patients. Twenty patients with TMD of myogenous origin and bruxism were divided into 2 groups treated with splints in maximum intercuspation (I) or centric relation (II). Clinical, electrognathographic and electromyographic examinations were performed before and 3 months after therapy. Data were analyzed by the Student's t test. Differences at 5% level of probability were considered statistically significant. There was a remarkable reduction in pain symptomatology, without statistically significant differences (p>0.05) between the groups. There was mandibular repositioning during therapy, as demonstrated by the change in occlusal contacts on the splints. Electrognathographic examination demonstrated a significant increase in maximum left lateral movement for group I and right lateral movement for group II (p<0.05). There were no significant differences (p>0.05) in the electromyographic activities at rest after utilization of both splints. In conclusion, both occlusal splints were effective for pain control and presented similar action. The results suggest that maximum intercuspation may be used for fabrication of occlusal splints in patients with occlusal stability without large discrepancies between centric relation and maximum intercuspation. Moreover, this technique is simpler and less expensive.

Role of flanking sequences and phosphorylation in the recognition of the simian-virus-40 large T-antigen nuclear localization sequences by importin-alpha

The nuclear import of simian-virus-40 large T-antigen (tumour antigen) is enhanced via phosphorylation by the protein kinase CK2 at Ser(112) in the vicinity of the NLS (nuclear localization sequence). To determine the structural basis of the effect of the sequences flanking the basic cluster KKKRK, and the effect of phosphorylation on the recognition of the NLS by the nuclear import factor importin-alpha (Impalpha), we co-crystallized non-autoinhibited Impalpha with peptides corresponding to the phosphorylated and non-phosphorylated forms of the NLS, and determined the crystal structures of the complexes. The structures show that the amino acids N-terminally flanking the basic cluster make specific contacts with the receptor that are distinct from the interactions between bipartite NLSs and Impalpha. We confirm the important role of flanking sequences using binding assays. Unexpectedly, the regions of the peptides containing the phosphorylation site do not make specific contacts with the receptor. Binding assays confirm that phosphorylation does not increase the affinity of the T-antigen NLS to Impalpha. We conclude that the sequences flanking the basic clusters in NLSs play a crucial role in nuclear import by modulating the recognition of the NLS by Impalpha, whereas phosphorylation of the T-antigen enhances nuclear import by a mechanism that does not involve a direct interaction of the phosphorylated residue with Impalpha.

Structural basis for the specificity of bipartite nuclear localization sequence binding by importin-alpha

Importin-alpha is the nuclear import receptor that recognizes cargo proteins carrying conventional basic monopartite and bipartite nuclear localization sequences (NLSs) and facilitates their transport into the nucleus. Bipartite NLSs contain two clusters of basic residues, connected by linkers of variable lengths. To determine the structural basis of the recognition of diverse bipartite NLSs by mammalian importin-alpha, we co-crystallized a non-autoinhibited mouse receptor protein with peptides corresponding to the NLSs from human retinoblastoma protein and Xenopus laevis phosphoprotein N1N2, containing diverse sequences and lengths of the linker. We show that the basic clusters interact analogously in both NLSs, but the linker sequences adopt different conformations, whereas both make specific contacts with the receptor. The available data allow us to draw general conclusions about the specificity of NLS binding by importin-alpha and facilitate an improved definition of the consensus sequence of a conventional basic/bipartite NLS (KRX10-12KRRK) that can be used to identify novel nuclear proteins.

Antiulcerogenic action of ethanolic extract of the resin from Virola surinamensis Warb. (Myristicaceae)

Ethnopharmacological relevance: Virola surinamensis (Myristicaceae), popularly known as mucuiba, ucuuba or ucuuba do igapo is a large tree that grows abundantly in Varzea forest and on river banks in the Brazilian states of Amazonas and Tocantins. The resin obtained by cuts on the stem bark is a reputed folk remedy in its natural form for the treatment of ulcer, gastritis inflammation and cancer.Aim of the study: The present work evaluated the pharmacological activity of the resin obtained from bark of V surinamensis as antiulcerogenic in experimental in vivo model in order to observe whether its traditional use is justified.Materials and methods: The preventive action of ethanolic extract of V surinamensis was evaluated in experimental in vivo models in rodents that simulated this disease in human gastric mucosa.Results: Oral administration of acidified ethanol solution produced severe hemorrhagic lesions in glandular mucosa with ulcerative lesion of 50 +/- 11.5 mm. In animals pretreated with V surinamensis (500 mg/kg, p.o.) a significant inhibition of mucosal injury of 2.40 +/- 0.56 mm (95% inhibition) was detected. The V. surinamensis, at the same dose, also reduced significantly (p < 0.05) the formation of gastric lesions induced by indomethacin (39%), stress (45%) and by pylorus ligature in mice (31%) when compared to animals treated with vehicle. The extract from V surinamensis exerts gastroprotective action only when this extract contacts gastric mucosa (oral route) with. increased pH values and reduced H(+) concentration of gastric contents. The ethanolic extract of V surinamensis resin was analyzed by TLC and spectrometric methods (NMR and ES-MS) and the main constituent of this extract was epicatechin.Conclusions: We suggest that the epicatechin present in V surinamensis resin may be among active principles responsible for the antiulcer activity shown by the tested resin but their used suggest carefulness because toxicological symptoms mentioned by population. (C) Published by Elsevier B.V.

Low-Resolution Molecular Models Reveal the Oligomeric State of the PPAR and the Conformational Organization of Its Domains in Solution

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

Dominance and Subordination Interactions Among Nestmates in Pre and Post-Emergence Phases of the Basal Eusocial Wasp Mischocyttarus (Monogynoecus) montei (Hymenoptera, Vespidae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Taxocenose de aves em um remanescente da Floresta com Araucária no Sudeste do Paraná, Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: Crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagous nematode Ancylostoma caninum

NAPc2, an anticoagulant protein from the hematophagous nematode Ancylostoma caninum evaluated in phase-II/IIa clinical trials, inhibits the extrinsic blood coagulation pathway by a two step mechanism, initially interacting with the hitherto uncharacterized factor Xa exosite involved in macromolecular recognition and subsequently inhibiting factor VIIa (K-i = 8.4 pM) of the factor VIIa/tissue factor complex. NAPc2 is highly flexible, becoming partially ordered and undergoing significant structural changes in the C terminus upon binding to the factor Xa exosite. In the crystal structure of the ternary factor Xa/NAPc2/selectide complex, the binding interface consists of an intermolecular antiparallel beta-sheet formed by the segment of the polypeptide chain consisting of residues 74-80 of NAPc2 with the residues 86-93 of factor Xa that is additional maintained by contacts between the short helical segment (residues 67-73) and a turn (residues 26-29) of NAPc2 with the short C-terminal helix of factor Xa (residues 233-243). This exosite is physiologically highly relevant for the recognition and inhibition of factor X/Xa by macromolecular substrates and provides a structural motif for the development of a new class of inhibitors for the treatment of deep vein thrombosis and angioplasty. (c) 2006 Elsevier Ltd. All rights reserved.