The role of contactin-associated protein-like 2 in neurodevelopmental disease and human cerebral cortex evolution

The contactin-associated protein-like 2 (CNTNAP2) gene is associated with multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability (ID), and specific language impairment (SLI). Experimental work has shown that CNTNAP2 is important for neuronal development and synapse formation. There is also accumulating evidence for the differential use of CNTNAP2 in the human cerebral cortex compared with other primates. Here, we review the current literature on CNTNAP2, including what is known about its expression, disease associations, and molecular/cellular functions. We also review the evidence for its role in human brain evolution, such as the presence of eight human accelerated regions (HARs) within the introns of the gene. While progress has been made in understanding the function(s) of CNTNAP2, more work is needed to clarify the precise mechanisms through which CNTNAP2 acts. Such information will be crucial for developing effective treatments for CNTNAP2 patients. It may also shed light on the longstanding question of what makes us human

Disponibilidade De Antídotos No Município De Campinas, São Paulo

The lack of availability of antidotes in emergency services is a worldwide concern. The aim of the present study was to evaluate the availability of antidotes used for treating poisoning in Campinas (SP). DESIGN AND SETTING: This was a cross-sectional study of emergency services in Campinas, conducted in 2010-2012. METHODS: The availability, amount in stock, place of storage and access time for 26 antidotal treatments was investigated. In the hospitals, the availability of at least one complete treatment for a 70 kg adult over the first 24 hours of admission was evaluated based on stock and access recommendations contained in two international guidelines. RESULTS: 14 out of 17 functioning emergency services participated in the study, comprising pre-hospital services such as the public emergency ambulance service (SAMU; n = 1) and public emergency rooms for admissions lasting ≤ 24 hours (UPAs; n = 3), and 10 hospitals with emergency services. Six antidotes (atropine, sodium bicarbonate, diazepam, phytomenadione, flumazenil and calcium gluconate) were stocked in all the services, followed by 13 units that also stocked activated charcoal, naloxone and diphenhydramine or biperiden. No service stocked all of the recommended antidotes; only the regional Poison Control Center had stocks close to recommended (22/26 antidotal treatments). The 10 hospitals had almost half of the antidotes for starting treatments, but only one quarter of the antidotes was present with stocks sufficient for providing treatment for 24 hours. CONCLUSION: The stock of antidotes for attending poisoning emergencies in the municipality of Campinas is incomplete and needs to be improved. © 2017, Associacao Paulista de Medicina. All rights reserved.13511522FAPEAM, Fundação de Amparo à Pesquisa do Estado do Amazona

Snakebites By Bothrops Spp In Children In Campinas, São Paulo, Brazil.

From January, 1984 to March, 1999, 73 children under 15 y old (ages 1-14 y, median 9 y) were admitted after being bitten by snakes of the genus Bothrops. Twenty-six percent of the children were classified as mild envenoming, 50.7% as moderate envenoming and 20.6% as severe envenoming. Two patients (2.7%) showed no signs of envenoming. Most of the patients presented local manifestations, mainly edema (94.5%), pain (94.5%) ecchymosis (73.9%) and blisters (11%). Local and/or systemic bleeding was observed in 28.8% of the patients. Before antivenom (AV) administration, blood coagulation disorders were observed in 60.7% (incoagulable blood in 39.3%) of the 56 children that received AV only in our hospital. AV early reactions, most of which were considered mild, were observed in 44.6% of these cases (in 15/30 patients not pretreated and in 10/26 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). The main clinical complications observed were local infection (15.1%), compartment syndrome (4.1%), gangrene (1.4%) and acute renal failure (1.4%). No deaths were recorded. There were no significant differences with regard to severity of envenoming versus the frequency of blood coagulation disorders among the three categories of envenoming (p = 0.75) or in the frequency of patients with AV early reactions between the groups that were and were not pretreated (p = 0.55). The frequency of local infection was significantly greater in severe cases (p < 0.001). Patients admitted more than 6 h after the bite had a higher risk of developing severe envenoming (p = 0.04).43329-3

A Clinico-epidemiological Study Of Bites By Spiders Of The Genus Phoneutrla

From January, 1984 to December, 1996, 422 patients (ages 9 m-99 y, median 29 y) were admitted after being bitten by spiders which were brought and identified as Phoneutria spp. Most of the bites occurred at March and April months (29.2%), in the houses (54.5%), during the day (76.5%), and in the limbs (feet 40.9%, hands 34.3%). Upon hospital admission, most patients presented only local complaints, mainly pain (92.1%) and edema (33.1%) and were classified as presenting mild (89.8%), moderate (8.5%) and severe (0.5%) envenomation. Few patients (1.2%) did not present signs of envenomation. Severe accidents were only confirmed in two children (9 m, 3 y). Both developed acute pulmonary edema, and the older died 9 h after the accident. Patients more than 70 yearold had a significantly greater (p<0.05) frequency of moderate envenomations compared to the 10-70-year-old individuals. Proceedings to relief local pain were frequently performed (local anesthesia alone 32.0%, local anesthesia plus analgesics 20.6% and oral analgesics alone 25.1%). Only 2.3% of the patients (two cases classified as severe and eight as noderate, eight of them in children) were treated with i.v. antiarachnid antivenom. No antivenom early reaction was observed. In conclusion, accidents involving the genus Phoneutria are common in the region of Campinas, with the highest risk groups being children under 10 years of age and adults over 70 years of age. Cases of serious envenomation are rare (0.5%).4211721Antunes, E., Marangoni, R.A., Brain, S.D., De Nucci, G., Phoneutria nigriventer (armed spider) venom induces increased vascular permeability in rat and rabbit skin in vivo (1992) Toxlcon, 30, pp. 1011-1016Antunes, E., Marangoni, R.A., Borges, N.C.C.T., Effects of Phoneutria nigriventer venom on rabbit vascular smooth muscle (1993) Braz. J. Med. Biol. Res., 26, pp. 81-91Bucaretchi, F.-., (1990) Análise das Principais Diferenças Clinicas e Epidemiológicas Dos Acidentes Por Escorplões Das Espécies Tityus Serrulatus e Tityus Bahiensis, e Por Aranhas do Gẽnero Phoneutria, Atendidos no CCI-HC-UNICAMP, no Período de Janeiro de 1984 a Julho de 1988, , Campinas, Dissertação de Mestrado -Faculdade de Ciẽncias Médicas da Universidade Estadual de CampinasBucaretchi, F., Acidentes por Phoneutria (1992) Plantas Venenosas e Animals Peçonhentos, pp. 196-201. , SCHVARTSMAN, S., ed. Sãu Paulo, SarvierBucaretchi, F., Collares, E.F., Effect of Phoneutria nigriventer spider venom on gastric emptying in rats (1996) Braz. J. Med. Biol. Res., 29, pp. 205-211Bücherl, W., A "armadeira": A aranha mais perigosa do mundo! (1985) Acúleos Que Matam, pp. 35-45. , BÜCHERL. W., ed. Rio De Janeiro. KosmosCosta, S.K.P., Moreno, J.R.H., Brain, S.D., The effect of Phoneutria nigriventer (armed spider) venom on arterial blood pressure of anaesthetised rats (1996) Europ. J. Pharmacol., 298, pp. 113-120Cruz-Hofling, M.A., Love, S., Brook, G., Duchen, L.W., Effects of Phoneutria nigriveter spider venom on mouse peripheral nerve (1985) Quart. J, Exp. Physlol., 70, pp. 623-640Fontana, M.D., Vital-Brazil, O., Mode of action of Phoneutria nigriventer spider venom at the isolated phrenic nerve-diaphragm of the rat (1985) Braz. J. Med. Biol. Res., 18, pp. 557-565Lopes-Martins, R.A.B., Antune, S.E., Oliva, M.L.V., Pharmacological characterization of rabbit corpus cavernosum relaxation mediated by the tissue kallikrein-kinin system (1994) Brit. J. Pharmacol., 113, pp. 81-86Lucas, M.S., Spiders in Brazil (1988) Toxicon, 26, pp. 759-772Marangoni, R.A., Antunes, E., Brain, S.D., De-Nucci, G., Activation by Phoneutria nigriventer (armed spider) venom of the tissue kallikrein-kininogen-kinin system in rabbit skin in viva (1993) Brit. J. Pharmacol., 109, pp. 539-543Acidentes por Phoneutria (1998) Manual de Diagnóstico e Tratamento de Acidentes Por Animals Peçonhentos, pp. 54-56. , Brasflia, Ministério da Saúde/Fundação Nacional da SaúdeAraneísmo (1998) Manual de Diagnóstico e Tratamento de Acidentes Por Animals Peçonhentos, pp. 49-53. , Brasfia, Ministério da Saúde/Fundação Nacional da SaúdeRamos, E.F., Almeida, C.E., Gouvêa, E., Carmo-Silva, M., Considernções sobre a atividade de locomoção, preferência por ecótopos e aspectos territoriais de phoneutria nigriventer (Keiserling, 1891) (1998) Rev. Bras. Biol., 58, pp. 71-78. , Aranae. CtenidaeRego, E., Bento, A.C., Lopes-Martins, A.B., Isolation and partial characterization of a polypeptide from Phoneutria nigriventer spider venom that relaxes rabbit corpus cavernosum in vitro (1996) Toxicon, 34, pp. 1141-1147Rosenfeld, G., Animais peçonhentos e tóxicos do Brasil (1972) Introdução à Geografia Médica do Brasil, pp. 430-475. , LACAZ. C.S.: BARUZZI, R.G. & SIQUEIRA Jr., W., ed. São Paulo, EDUSPVellard, J., Les araignées vraies. Les ctènes (1936) Le Venin des Araignèes. Monographies de L'institut Pasteur, pp. 169-184. , VELLARD, J., ed. Paris. MassonVital-Brazil, Vellard, J., Contribuição ao estudo do veneno das aranhas. II. Mem. Inst (1926) Butantan, 2, pp. 3-77Vital-Brazil, O., Bernardo-Leite, G.B., Fontana, M., Modo de ação da peçonha da aranha armadeira, phoneutria nigriventer (Keiserling, 1891), nas aurífculas isoladas de cobain (1988) Ciênc. Cult., 40, pp. 181-18

N-Alkyl-α-amino acids in Nature and their biocatalytic preparation

PWS would like to acknowledge the European Union for his current funding: “This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 665919”.N-alkylated-α-amino acids are useful building blocks for the pharmaceutical and fine chemical industries. Enantioselective methods of N-alkylated-α-amino acid synthesis are therefore highly valuable and widely investigated. While there are a variety of chemical methods for their synthesis, they often employ stoichiometric quantities of hazardous reagents such as pyrophoric metal hydrides or genotoxic alkylating agents, whereas biocatalytic routes can provide a greener and cleaner alternative to existing methods. This review highlights the occurrence of the N-alkyl-α-amino acid motif and its role in nature, important applications towards human health and biocatalytic methods of preparation. Several enzyme classes that can be used to access chiral N-alkylated-α-amino acids and their substrate selectivities are detailed.PostprintPeer reviewe

Spectrum of the Y=2 Pentaquarks

By assuming a mass formula for the spectrum of the Y=2 pentaquarks, where the chromo-magnetic interaction plays a main role, and identifying the lightest state with the Theta^+(1540), we predict a spectrum in good agreement with the few I=0 and I=1 candidates proposed in the past.Comment: 12 pages, 4 figures, LaTe

A Clinico-epidemiological Study Of Bites By Spiders Of The Genus Phoneutria.

From January, 1984 to December, 1996, 422 patients (ages 9 m-99 y, median 29 y) were admitted after being bitten by spiders which were brought and identified as Phoneutria spp. Most of the bites occurred at March and April months (29.2%), in the houses (54.5%), during the day (76.5%), and in the limbs (feet 40.9%, hands 34.3%). Upon hospital admission, most patients presented only local complaints, mainly pain (92.1%) and edema (33.1%) and were classified as presenting mild (89.8%), moderate (8.5%) and severe (0.5%) envenomation. Few patients (1.2%) did not present signs of envenomation. Severe accidents were only confirmed in two children (9 m, 3 y). Both developed acute pulmonary edema, and the older died 9 h after the accident. Patients more than 70 year-old had a significantly greater (p<0.05) frequency of moderate envenomations compared to the 10-70-year-old individuals. Proceedings to relief local pain were frequently performed (local anesthesia alone 32.0%, local anesthesia plus analgesics 20.6% and oral analgesics alone 25. 1%). Only 2.3% of the patients (two cases classified as severe and eight as moderate, eight of them in children) were treated with i.v. antiarachnid antivenom. No antivenom early reaction was observed. In conclusion, accidents involving the genus Phoneutria are common in the region of Campinas, with the highest risk groups being children under 10 years of age and adults over 70 years of age. Cases of serious envenomation are rare (0.5%).4217-2

Constraints on narrow exotic states from K+p and K0_Lp scattering data

We consider the effect of exotic S=+1 resonances Theta+ and Theta++ on K+p elastic scattering data (total cross section) and the process K0_Lp-->K0_Sp. Data near the observed Theta+(1540) are examined for evidence of additional states. The width limit for a Theta++ state is reconsidered and shown to be much less than 1 MeV.Comment: 4 pages, 3 eps figures; minor corrections, one fig adde

Estimativa do fator topográfico da Equação Universal de Perda de Solo (usle) utilizando o InVest, na bacia Piririm, Amapá.

O objetivo deste trabalho foi delimitar a bacia hidrográfica do rio Piririm, no estado do Amapá, bem como calcular o fator topográfico (LS) da Universal Soil Loss Equation (USLE), utilizando o software InVEST (Integrated Valuation of Ecossystem Services and Tradeoffs). Essa bacia é uma das áreas de estudo do projeto ?Construção do conhecimento e sistematização de experiências sobre valoração e pagamento por serviços ecossistêmicos e ambientais no contexto agricultura familiar amazônica (Aseam)?. A bacia foi delimitada utilizando sistema de informações geográficas (SIG) com base em modelo digital de terreno (MDT) de resolução espacial de 2,5 m. Os arquivos foram trabalhados no SIG ArcGIS 10.6.1 e no software InVEST 3.6.0, utilizando a extensão ArcHydro Tools e a ferramenta DelineateIT, respectivamente. O fator topográfico da USLE foi mapeado utilizando o módulo SDR (Sediment Delivery Ratio) do InVEST. O InVEST possibilitou a delimitação da bacia do Rio Piririm de forma simples e com alta precisão. O módulo SDR estimou o fator topográfico (LS) da USLE com a vantagem de ser um software livre e com grande potencial de valoração para serviços ambientais e ecossistêmicos. A média do fator LS na bacia foi de 0,787, enquanto o maior valor computado foi de 97,494. As áreas com maiores valores de LS apresentam maior risco de erosão hídrica e, portanto, seu manejo deve ser mais criterioso. O software InVEST atendeu as demandas propostas neste trabalho e apresenta grande potencial para alcançar os objetivos previstos no projeto Aseam, financiado pelo Fundo Amazôni

Surface-reconstructed Icosahedral Structures for Lead Clusters

We describe a new family of icosahedral structures for lead clusters. In general, structures in this family contain a Mackay icosahedral core with a reconstructed two-shell outer-layer. This family includes the anti-Mackay icosahedra, which have have a Mackay icosahedral core but with most of the surface atoms in hexagonal close-packed positions. Using a many-body glue potential for lead, we identify two icosahedral structures in this family which have the lowest energies of any known structure in the size range from 900 to 15000 lead atoms. We show that these structures are stabilized by a feature of the many-body glue part of the interatomic potential.Comment: 9 pages, 8 figure