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This work describes the synthesis and characterization of 2-aminothiazole-modified titania and its application on Hg (II) photoreduction in aqueous medium. Infrared spectroscopy confirmed the chemical modification of the titania matrix. The number of 2-aminothiazole groups attached to the titania was determined by Kjeldahl's method. The photocatalytic experiments were carried out in a cylindrical photoreactor thermostatted at 298 K. The resulting modified photocatalyst 2-aminothiazole titania (TiAT) revealed an enhance in the Hg (II) photoreduction capacity at studied pH values (3, 7 and 9). In addition, sorption studies showed that the photocatalyst TiAT presented a lower equilibrium time and a higher sorption capacity of Hg(II) ion, demonstrating that sorption plays a fundamental role in the photoreduction mechanism.

O objetivo deste trabalho foi avaliar a sobrevivência e a capacidade de nodulação do Rhizobium tropici em sementes de feijão tratadas com fungicidas. O estudo foi realizado em laboratório e em casa de vegetação. Sementes de feijão (Phaseolus vulgaris) foram tratadas com seis diferentes fungicidas e inoculadas com Rhizobium tropici estirpe CIAT 899. A sobrevivência do Rhizobium nas sementes foi avaliada no tempo 0 e 24 horas após o tratamento com fungicidas e a inoculação, utilizando o método do número mais provável (NMP). A nodulação do feijão, em plantio realizado no tempo 0 e 24 horas após o tratamento com fungicidas, e a inoculação foram avaliadas em solo com população estabelecida de Rhizobium nativo aos trinta dias após a emergência das plantas. A sobrevivência do Rhizobium inoculado nas sementes foi prejudicada pela aplicação dos fungicidas avaliados. A nodulação do feijoeiro foi reduzida pela aplicação dos fungicidas, quando o plantio foi realizado 24 horas após o tratamento das sementes. Entretanto, foram encontrados nódulos em todos os tratamentos, evidenciando que houve nodulação do Rhizobium nativo do solo.

O objetivo deste trabalho foi avaliar o aproveitamento do nitrogênio de adubo verde (Crotalaria juncea L.)-15N e da uréia-15N, em fertilização conjugada e separada. O experimento foi conduzido em vasos contendo 5kg de um Latossolo Vermelho distrófico típico (amostra colhida na profundidade de 0-20cm), utilizando trigo (Triticum aestivum L.), cultivar IAC-24. O delineamento inteiramente casualizado foi usado com 5 tratamentos e 4 repetições: T1 - uréia-15N (45mg kg-1 de N-uréia); T2 - Crotalaria juncea-15N (100mg kg-1de N-crotalária); T3 - Crotalaria juncea-14N (100mg kg-1de N-crotalária) e uréia-15N (45mg kg-1 de N-uréia); T4 - uréia-14N (45mg kg-1 de N-uréia) e Crotalaria juncea-15N (100mg kg-1de N-crotalária); T5 - tratamento controle (sem adição de fontes de N). A colheita das plantas de trigo foi realizada aos 50 dias após a emergência (DAE), no estádio de florescimento, separando-se a parte aérea do sistema radicular, sendo também amostrado o solo de cada vaso. Os parâmetro avaliados foram a massa de material seco, altura de plantas, conteúdo de N e abundância de 15N, sendo calculada a recuperação do nitrogênio proveniente das fontes. A recuperação do N-uréia nas plantas de trigo foi maior que o N-crotalária, que permaneceu imobilizado no solo. No sistema solo-planta, a recuperação do N-crotalária foi igual ao N-uréia. A fertilização do solo com uréia conjugada à crotalária ou aplicada separadamente, resultou em maior massa de material seco e conteúdo de N-total nas plantas de trigo. A utilização da Crotalaria juncea como fonte de nitrogênio pode ser uma alternativa para ampliar a conservação do nutriente no sistema solo-planta.

No presente trabalho procurou-se conhecer o perfil das enteroparasitoses na cidade de São Raimundo Nonato, sudeste do Piauí, e confirmar ou não os resultados obtidos em estudos anteriores em relação à infecção por Ascaris lumbricoidese Trichuris trichiura. No período de setembro de 2000 a fevereiro de 2001, por meio de amostragem domiciliar por conveniência, foram examinadas 265 amostras fecais da população pelo método de sedimentação espontânea, das quais 57% foram positivas para enteroparasitos. Entamoeba coli (35,8%), Endolimax nana (13,6%), Hymenolepis nana (9,4%) e os ancilostomídeos (9,4%) foram os parasitos mais freqüentes. Foram observados dois casos de A. lumbricoides, possivelmente adquiridos fora do município. Nenhuma amostra foi positiva para T. trichiura. Esses resultados mostram um padrão diferente do restante do país. Traça-se um paralelo entre os resultados deste estudo com os achados paleoparasitológicos na população pré-histórica, habitante da região há pelo menos sete mil anos.

FUNDAMENTOS: As dermatomicoses causadas por fungos emergentes são entidades clínicas raras, à exceção das onicomicoses. Como certos fungos e leveduras podem residir na pele, a positividade em culturas de escamas ungueais deve ser interpretada obrigatoriamente em concordância com os respectivos dados clínicos, exames diretos das amostras, quantificação das colônias isoladas em relação aos pontos de inoculação e, principalmente, deve a positividade ser mantida após a repetição dos cultivos. A invasão da unha por fungos não dermatofíticos (nondermatophytic molds, NDM) em diferentes estudos varia de 1,45% a 17,6%. OBJETIVOS: Os objetivos do trabalho são mostrar a ocorrência e realçar a importância dos fungos emergentes como causadores de onicomicose. MÉTODOS: As unhas dos pacientes atendidos nos consultórios dos dermatologistas foram examinadas, e, caso houvesse suspeita clínica de onicomicose, coletavam-se amostras que eram enviadas para exame micológico no laboratório. RESULTADOS: Neste estudo, foram avaliados 2.271 pacientes e diagnosticada onicomicose em 400 deles, sendo 264 com acometimento das unhas do pé, e 136 das unhas da mão. O agente etiológico foi confirmado pelo exame micológico direto e crescimento em cultura. A onicomicose por fungos emergentes representou 4,5% de todas as infecções de unha. Foram detectadas as leveduras do gênero Candida (49%) como agentes etiológicos mais freqüentes de onicomicoses nas unhas das mãos e em mulheres. Em contraste, os dermatófitos foram os mais freqüentes de todas as onicomicoses dos pés, no total de 186 (46,5%). CONCLUSÃO: Ao contrário da rotina diagnóstica hoje utilizada, concluiu-se que o diagnóstico correto do agente etiológico da onicomicose não dermatofítica deve obedecer a determinados critérios, dos quais se destaca o conjunto formado pela positividade no exame direto, na cultura, com comprovação na repetição do exame.

O efeito do ambiente e do genótipo foi estudado em dez fazendas particulares no Estado do Ceará, em 480 ovelhas Crioulas, 48 carneiros Santa Inês e 1474 cordeiros F1. As características estudadas foram taxas de acasalamento, fertilidade ao parto, prolificidade e desmame, bem como os pesos ao nascer, 56, 84 e 112 dias de idade e os ganhos diários de peso do nascimento aos 56, dos 56 aos 84 e do nascimento aos 112 dias de idade. Houve efeito significativo da raça sobre as taxas de acasalamento, fertilidade e desmame, sendo que as ovelhas F1 produziram menos cordeiros que as Crioulas. Houve efeito significativo da idade das ovelhas e da fazenda sobre todas as características estudadas, exceto o efeito da idade da ovelha sobre a taxa de desmame. Os pesos e os ganhos de peso na fase de crescimento, de modo geral, foram influenciados pelo ano de nascimento, tipo de nascimento, fazenda e reprodutor dentro de fazenda. As estimativas de herdabilidades para os pesos variam de 0,36 a 0,53, mostrando que existe grande possibilidade para se melhorar a taxa de ganho de peso dos cordeiros cruzados por meio de seleção.

OBJETIVO: A presença de resíduos de praguicidas em alimentos, somada à contaminação da água, oferece risco para a população em geral e representa, sem dúvida, um grande problema de saúde pública no Brasil. Com o objetivo de obter melhor conhecimento da situação, foi estudada a utilização de praguicidas em tomates produzidos no Estado de Pernambuco. MÉTODOS: Foram aplicados questionários semi-estruturados para obtenção de informações socioambientais e de morbidade referida aos trabalhadores rurais, durante a safra de tomates. Foram selecionadas seis propriedades, localizadas em duas regiões produtoras do agreste pernambucano. O total de entrevistados foi de 186. RESULTADOS/CONCLUSÕES: Ficou constatado que as duas regiões estudadas carecem, indiscriminadamente, de ações que visem à proteção da saúde dos trabalhadores rurais, que lidam com os praguicidas, e de medidas contra os danos para o meio ambiente, que se encontra gravemente comprometido.

O estudo foi realizado para avaliar as características produtivas dos caprinos mestiços submetidos às condições climáticas do semi-árido nordestino. Foram utilizadas 657 cabras, as quais foram mantidas em pasto nativo, no período seco, e alimentadas com milho e farelo de soja, e 945 crias mestiças, que foram aleitadas com leite de vaca até 24 horas de vida. As médias das cabras para prolificidade e peso ao parto foram respectivamente 1,69+0,03 e 36,38+0,03 kg, para ½ Pardo Alpina (PA) + ½ Moxotó (MO); 1,59+0,05 e 36,24+0,58 kg, para ¾ PA + ¼ MO; e 1,78+0,04 e 37,25+0,46 kg, para ½ Anglo Nubiana (NA) + ¼ PA + ¼ MO (Tricross). As médias de peso das crias ao nascer, aos 28, 56 e 84 dias de idade, foram respectivamente 2,26+0,04; 4,02+0,07; 6,93+0,14; e 10,97+0,03 kg, para ½ PA + ½ MO, 2,46+0,03; 4,32+0,05; 7,85+0,10 kg; e 12,18+0,19 kg, na mesma ordem de peso, para ¾ PA + ¼ MO e 2,46+0,03; 4,30+0,04; 7,48+0,09; e 11,86+0,17 kg, também na mesma ordem de peso, para Tricross. As cabras mestiças apresentaram prolificidade semelhante às nativas. As crias ¾ Pardo Alpina e as Tricross foram mais pesadas que as crias ½ Pardo Alpina + ½ MO, provavelmente em função do maior percentual de sangue exótico observado nestes dois grupos genéticos.

O objetivo deste estudo foi analisar algumas características dos domicílios e dos chefes de família como possíveis fatores de determinação da hanseníase. Compararam-se unidades domiciliares onde existiam casos de hanseníase com dois grupos de domicílios de não hansenianos. Como grupos de domicílios sem casos de hanseníase, estudaram-se os domicílios vizinhos dos doentes e os domicílios fora dos focos ou áreas sem casos de hanseníase. Todos os domicílios localizam-se no município de São Gonçalo, área endêmica urbana na periferia da região metropolitana do Rio de Janeiro. Em um mapa aerofotogramétrico, contendo a descrição dos 584 setores censitários, marcaram-se todos os 2412 casos diagnosticados residentes. Compararam-se os domicílios com casos de hanseníase, Grupo I, com os seus respectivos vizinhos (Grupo II) e com os domicílios fora do foco (Grupo III). Os domicílios do Grupo I foram pareados com os seus respectivos vizinhos (Grupo II) e processados pelo método condicional. Para a comparação entre os grupos I e grupo III, usou-se o método incondicional. O Grupo I comparado com o II apresentou associação entre idade e nível de escolaridade do chefe da família. A comparação das características dos chefes de família e dos domicílios com casos de hanseníase em relação aos localizados fora do foco mostrou, como fatores diferenciais, idade, tipo de casa e disponibilidade de pontos de água intradomiciliar. Os autores discutem que os contrastes da área fora do foco são indicativos de um assentamento populacional mais recente e não de fatores associados à hanseníase. Somente na análise pareada dos doentes com seus vizinhos, estando então os fatores ambientais da área de foco controlados, confirmou-se a associação da idade e do grau de escolaridade. Com os determinantes do nível particular próprio do grupo social, interagem, no nível individual, a idade e o grau de escolaridade como fatores que contribuem na morbidade da hanseníase nessa área do Estado do Rio de Janeiro.

The Solvay Process is an important route for the industrial preparation of sodium carbonate from brine and CO2. However, experiments illustrating such process are performed only in a few chemistry courses, mainly because of the difficulties to precipitate out the intermediate product NaHCO3 within the 3 or 4 hours generally available for laboratory classes. In this article we describe a method that properly simulates the Solvay process using glass apparatus that can be found in any chemistry laboratory. The good yields and purity attainable, associated with the short time (~3 hours) required to get the sodium bicarbonate, account for the suitability of our method for chemistry or chemical engineering undergraduate students laboratory classes.

Abstract Background Analyses of coprolites have contributed to the knowledge of diet as well as infectious diseases in ancient populations. Results of paleoparasitological studies showed that prehistoric groups were exposed to spurious and zoonotic parasites, especially food-related. Here we report the findings of a paleoparasitological study carried out in remote regions of Brazil’s Northeast. Findings Eggs of Pharyngodonidae (Nematoda, Oxyuroidea), a family of parasites of lizards and amphibians, were found in four human coprolites collected from three archaeological sites. In one of these, lizard scales were also found. Conclusions Through the finding of eggs of Pharyngodonidae in human coprolites and reptile scales in one of these, we have provided evidence that humans have consumed reptiles at least 10,000 years ago. This food habit persists to modern times in remote regions of Brazil’s Northeast. Although Pharyngodonidae species are not known to infect humans, the consumption of raw or undercooked meat from lizards and other reptiles may have led to transmission of a wide range of zoonotic agents to humans in the past.

Abstract Since the original description and naming of Ascaris lumbricoides from humans by Linnaeus in 1758 and later of Ascaris suum from pigs by Goeze 1782, these species have been considered to be valid. Four hypotheses relative to the conspecificity or lack thereof (and thus origin of these species) are possible: 1) Ascaris lumbricoides (usually infecting humans) and Ascaris suum (recorded mostly from pigs) are both valid species, with the two species originating via a speciation event from a common ancestor sometime before the domestication of pigs by humans, or 2) Ascaris lumbricoides in humans is derived directly from the species A. suum found in pigs with A. suum then existing as a persistent ancestor after formation of A. lumbricoides, or 3) Ascaris suum is derived directly from A. lumbricoides with the persistent ancestor being A. lumbricoides and A. suum being the newly derived species, and finally, 4) Ascaris lumbricoides and A. suum are the same species, this hypothesis being supported by studies showing both low morphological and low genetic divergence at several genes. We present and discuss paleoparasitological and genetic evidence that complement new data to evaluate the origin and evolution of Ascaris spp. in humans and pigs, and the uniqueness of the species in both hosts. Finally, we conclude that Ascaris lumbricoides and A. suum are a single species and that the name A. lumbricoides Linnaeus 1758 has taxonomic priority; therefore A. suum Goeze 1782 should be considered a synonym of A. lumbricoides.

Ocean warming is expected to occur due to anthropogenic climate change bringing a spatial shift of marine communities. Experimental data that characterize the aerobic power budget via an aerobic scope, thermal metabolic scope, or thermal preferences have been proposed as tools that can describe species distribution since they characterize species fitness or performance under different temperatures. This study tested the potential relationship between observed occurrences and different physiological studies in the Americas for 11 commercially important species in Mexico. Projections were also developed for Mexico's exclusive economic zone under different climate warming scenarios. The physiological data were fitted from optimum up to pejus temperatures and projected to sea surface temperatures for present (2003-2014) and Representative Concentration Pathway (RCP) scenarios (RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5) for the period 2040-2050 and 2090-2100. For species with wide distributions in the Americas, the number of occurrences reported decreases at higher latitudes related to the decrease in species performance calculated from laboratory experiments. In addition, higher species occurrences are usually reported around optimum temperatures. Overall, the results suggest that pejus temperatures likely restrict latitudinal distribution, at least for widely distributed taxons. Regarding Mexican projections, the results varied widely by species. For example, in the Atlantic Ocean, Octopus maya and Panulirus argus are vulnerable to warming scenarios, while Centropomus undecimalis is not. Interestingly, northern Campeche Bank, the Gulf of California, and Western Baja California may act as thermal refugia for marine species indicating they could be assigned as protected areas to support fisheries throughout the Mexican exclusive economic zone. This research adds to the increasing evidence of the relationship between thermal niche and wild population distribution., Competing Interests: Declaration of competing interest No potential conflicts of interest were disclosed., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Multiple sclerosis (MS) is an inflammatory, degenerative, demyelinating disease that ranges from benign to rapidly progressive forms. A striking characteristic of the disease is the clinical-radiological paradox., Objectives: The present study was conducted to determine whether, in our cohort, the clinical-radiological paradox exists and whether lesion location is related to clinical disability in patients with MS., Methods: Retrospective data from 95 patients with MS (60 women and 35 men) treated at a single center were examined. One head-and-spine magnetic resonance imaging (MRI) examination from each patient was selected randomly, and two independent observers calculated lesion loads (LLs) on T2/fluid attenuation inversion recovery sequences manually, considering the whole brain and four separate regions (periventricular, juxtacortical, posterior fossa, and spinal cord). The LLs were compared with the degree of disability, measured by the Kurtzke Expanded Disability Status Scale (EDSS), at the time of MRI examination in the whole cohort and in patients with relapsing-remitting (RR), primarily progressive, and secondarily progressive MS., Results: High LLs correlated with high EDSS scores in the whole cohort (r = 0.34; p  < 0.01) and in the RRMS group (r = 0.27; p  = 0.02). The EDSS score correlated with high regional LLs in the posterior fossa (r = 0.31; p  = 0.002) and spinal cord (r = 0.35; p  = 0.001)., Conclusions: Our results indicate that the clinical-radiological paradox is a myth and support the logical connection between lesion location and neurological repercussion., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The present work aimed to study ecological aspects related to the distribution pattern of medically important and native freshwater mollusks, found in a rural municipality in the state of Minas Gerais, Brazil. Malacological captures were carried out in aquatic environments (lentic and lotic) from 46 locations between October 2018 and September 2019. The collected specimens were subjected to taxonomic identification and evaluation for infection with trematode larvae. Qualitative data were used to analyze the similarity and the odds ratios between the environmental variables. In total, 1125 specimens were sampled, belonging to the following species: Biomphalaria glabrata, B. tenagophila, B. straminea, B. kuhniana, B. cousini, Biomphalaria sp., and Drepanotrema cimex (Planorbidae), Stenophysa marmorata (Physidae), Omalonyx sp. (Succineidae), Pseudosuccinea columella (Lymnaeidae), and Pomacea sp. (Ampullaridae). Echinostome, strigeocercaria, and xiphidiocercaria types of larval trematodes were detected in S. marmorata and D. cimex . Of note was the similarity in the distribution of S. marmorata , a supposedly endangered species, with that of the medically important Biomphalaria species, with the two sharing environments. This complex scenario led us to reflect on and discuss the need for the control of important intermediate hosts, as well as the conservation of endangered species. This relevant issue has not yet been discussed in detail, in Brazil or in other countries that recommend snail control.

Aromatic groups are key mediators of protein-membrane association at cell surfaces, contributing to hydrophobic effects and π-membrane interactions. Here we show electrostatic and hydrophobic influences of aromatic ring substituents on membrane affinity and cell uptake of helical, cyclic and cell penetrating peptides. Hydrophobicity is important, but subtle changes in electrostatic surface potential, dipoles and polarizability also enhance association with phospholipid membranes and cell uptake. A combination of fluorine and sulfur substituents on an aromatic ring induces microdipoles that enhance cell uptake of 12-residue peptide inhibitors of p53-HDM2 interaction and of cell-penetrating cyclic peptides. These aromatic motifs can be readily inserted into peptide sidechains to enhance their cell uptake., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Crassostrea virginica was exposed to different light crude oil levels to assess the effect on transcriptomic response and metabolic rate. The exposure time was 21 days, and levels of 100 and 200 μg/L were used, including a control. The most significant difference among treatments was the overexpression of several genes associated with energy production, reactive oxygen species (ROS) regulation, immune system response, and inflammatory response. Also, a hydrocarbon concentration-related pattern was identified in ROS regulation, with a gene expression ratio near 1.8:1 between 200 and 100 μg/L treatments. Statistical analysis showed no interaction effect for metabolic rate; however, significant differences were found for oil concentration and time factors, with a higher oxygen consumption at 200 μg/L. Our findings provide novel information about the metabolic response of C. virginica during hydrocarbons exposure. In addition, our results point out which biological processes should be investigated as targets for searching bioindicators., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cyclic peptides that modulate protein-protein interactions can be valuable therapeutic candidates if they can be delivered intact to their target proteins in cells. Here we systematically compare the effects of different helix-inducing cyclization constraints on the capacity of a macrocyclic peptide component to confer α-helicity, protein-binding affinity, resistance to degradative proteases and cell uptake to a 12-residue peptide fragment of tumor suppressor protein p53. We varied the helix-inducing constraint (hydrocarbon, lactam, aliphatic or aromatic thioether, etc. ) and the position of the cyclization linker ( i to i + 4 or i to i + 7 bridges) in order to sculpt the macrocyclic size, stabilize its structure, and promote cell uptake. We find that rigidifying the macrocycle leads to higher alpha helicity, target affinity and proteolytic stability to different extents, whereas cell uptake of compounds shown here is mostly driven by hydrophobicity and aromaticity of the macrocycle., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Background: The genetic predisposition to multiple sclerosis (MS) is associated with HLA alleles, especially HLA-DRB1*15:01., Objective: To identify associations between findings in magnetic resonance imaging (MRI) and genetic features in a Brazilian cohort of patients with MS., Methods: We retrospectively studied data from 95 consecutive patients with MS. Two independent observers who were blinded to the clinical data identified black holes and enhanced lesions on T1 MRI sequences, and counted and measured contrast-enhanced lesions on T2 and Flair (fluid attenuation inversion recovery) sequences. Cases were classified according to lesion size, number, and volume. The HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the rs4774, rs3087456, rs6897932, rs731236, and rs1033182 single nucleotide polymorphisms were identified by polymerase chain reaction amplification with sequence-specific primers using the One Lambda Inc. Kit, Canoga Park, CA, USA., Results: Patients with the HLA-DQA1*04:01 allele had lesion load (adjusted for age, sex, and MS duration) above median compared with patients with other HLA-DQA1 alleles (p=0.02). There were no differences among all the other HLA alleles and single nucleotide polymorphisms and lesion load., Conclusions: The correlation of the HLA-DQA1*04:01 allele with a higher lesion load on T2/Flair MRI sequences suggests that the presence of this allele is associated with the risk of greater MS severity.

nvestigations of thermal limits are crucial to understanding climate change ecology because it illuminates how climate will shape future species distributions. This work determined the preferred temperature, critical threshold limits represented by the Critical Thermal Maximum (CTMax) and (CTMin), thermal window, oxygen consumption rate and thermal metabolic scope of Kelletia kelletii acclimated to 13, 16.0, 19.0 and 22.0 ± 1°C to determine if this species is sensitive to global warming. The preferred temperature (PT) of Kellet's whelk was determined using the acute method. The acclimation temperature significantly affected the thermal preference of the marine snail ( P < 0.05) and increased from 13.2 to 24.2°C as the acclimation temperature increased from 13.0 to 22.0°C. The PT was 13.4°C. The acclimation temperature did not significantly affect the CTMax ( P > 0.05), obtaining a range of 29.2 to 30.2°C. The CTMin had an interval of 9.2°C, at acclimation temperatures of 13 to 16°C, and increased significantly ( P < 0.05) at 12.3°C in the acclimation interval of 19-22°C. The thermal window for the different acclimation temperatures was 163.5°C 2 . The oxygen consumption rate of the snails increased significantly ( P < 0.05) when the acclimation temperature increased from 13.0 to 22.0°C, peaking at 63.6 mg of O 2 kg -1 h -1 w.w. in snails maintained at the highest acclimation temperature. The thermal metabolic scope increased significantly ( P < 0.05) when the acclimation temperature was 13.0°C, with values of 68.7 mg O 2 h -1 kg -1 w.w., then decreased significantly ( P < 0.05) to 27.9 mg O 2 h -1 kg -1 w.w at 32°C. Therefore, the thermal aerobic scope was highest at the temperatures that K. kelletii preferred. These results may partially explain their pattern of distribution on the Baja California coast.

This study determined the physiological and metabolic responses of cultivated Yellowtail Kingfish (Seriola lalandi) juveniles in accordance with their recent thermal history. The fish were acclimated at 20, 23, 26, 29 and 32 °C for 21 days to determine the final preferred temperature, thermal tolerance and the effect of acclimation temperatures on their oxygen uptake and aerobic scope. The final preferred temperature of juveniles was established at 26 °C. The critical thermal maximum (CTmax) ranged from 34.2 to 36.9 °C, while the critical thermal minimum (CTmin) ranged from 10.9 to 17.3 °C, depending on acclimation temperature. With the CTmax and CTmin values, the thermal window was determined to have an area of 258°C 2 , which is characteristic of subtropical organisms. Although, the metabolic rate was relatively constant (ranging 390.6-449.8 mg O 2 kg -0.8 h -1 ) between 20 and 26 °C (Q 10  = 1.6, 1.0), an increase to 544.8 mg O 2 kg -0.8  h -1  at 29 °C (Q 10  = 1.9) and decrease of 478.4 mg O 2 kg -0.8  h -1  at 32 °C (Q 10  = 0.6) were observed. The maximum value obtained for aerobic scope was 310.9 mg O 2 kg -0.8  h -1  at 26 °C. These results suggest that the acclimation temperature of 26 °C is an optimum thermal condition for a physiological and metabolic performance of yellowtail kingfish juveniles. On the contrary, the response observed during the evaluation of critical temperatures, oxygen uptake and aerobic scope indicated that yellowtail kingfish in the juvenile state could be vulnerable when it experiences for long periods (e.g., >21 days) temperatures above 29 °C. According to our results, the thermoregulatory behaviour of yellowtail kingfish in the juvenile stages could be one of the most important mechanisms to maintain its optimal physiological performance by actively selecting a stable thermal environment close to 26 °C. In addition, it was determined the limits of the pejus state of juvenile yellowtail kingfish at 29 °C, where an increase of oxygen uptake to maintain the aerobic energy metabolism was observed, this could certainly affect the growth of juveniles in culture systems if they do not return in a thermal range of 23-26 °C. These results can contribute to infer the different effects of acclimation temperature on the growth, thermal tolerance and respiratory capacity of S. lalandi juveniles on aquaculture systems., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The conventional S-alkylation of cysteine relies upon using activated electrophiles. Here we demonstrate high-yielding and selective S-alkylation and S-lipidation of cysteines in unprotected synthetic peptides and proteins by using weak electrophiles and a Zn 2+ promoter. Linear or branched iodoalkanes can S-alkylate cysteine in an unprotected 38-residue Myc peptide fragment and in a 91-residue miniprotein Omomyc, thus highlighting selective late-stage synthetic modifications. Metal-assisted cysteine alkylation is also effective for incorporating dehydroalanine into unprotected peptides and for peptide cyclisation via aliphatic thioether crosslinks, including customising macrocycles to stabilise helical peptides for enhanced uptake and delivery to proteins inside cells. Chemoselective and efficient late-stage Zn 2+ -promoted cysteine alkylation in unprotected peptides and proteins promises many useful applications., (© 2021 Wiley-VCH GmbH.)

Coiled coils (CCs) are powerful supramolecular building blocks for biomimetic materials, increasingly used for their mechanical properties. Here, we introduce helix-inducing macrocyclic constraints, so-called staples, to tune thermodynamic and mechanical stability of CCs. We show that thermodynamic stabilization of CCs against helix uncoiling primarily depends on the number of staples, whereas staple positioning controls CC mechanical stability. Inserting a covalent lactam staple at one key force application point significantly increases the barrier to force-induced CC dissociation and reduces structural deformity. A reversible His-Ni 2+ -His metal staple also increases CC stability, but ruptures upon mechanical loading to allow helix uncoiling. Staple type, position and number are key design parameters in using helical macrocyclic templates for fine-tuning CC properties in emerging biomaterials., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

c-Myc is a transcription factor that is constitutively and aberrantly expressed in over 70% of human cancers. Its direct inhibition has been shown to trigger rapid tumor regression in mice with only mild and fully reversible side effects, suggesting this to be a viable therapeutic strategy. Here we reassess the challenges of directly targeting c-Myc, evaluate lessons learned from current inhibitors, and explore how future strategies such as miniaturisation of Omomyc and targeting E-box binding could facilitate translation of c-Myc inhibitors into the clinic.

Spider venoms are a rich source of insecticidal peptide toxins. Their development as bioinsecticides has, however, been hampered due to concerns about potential lack of stability and oral bioactivity. We therefore systematically evaluated several synthetic strategies to increase the stability and oral potency of the potent insecticidal spider-venom peptide ω-HXTX-Hv1a (Hv1a). Selective chemical replacement of disulfide bridges with diselenide bonds and N- to C-terminal cyclization were anticipated to improve Hv1a resistance to proteolytic digestion, and thereby its activity when delivered orally. We found that native Hv1a is orally active in blowflies, but 91-fold less potent than when administered by injection. Introduction of a single diselenide bond had no effect on the susceptibility to scrambling or the oral activity of Hv1a. N- to C-terminal cyclization of the peptide backbone did not significantly improve the potency of Hv1a when injected into blowflies and it led to a significant decrease in oral activity. We show that this is likely due to a dramatically reduced rate of translocation of cyclic Hv1a across the insect midgut, highlighting the importance of testing bioavailability in addition to toxin stability.

Most protein-protein interactions occur inside cells. Peptides can inhibit protein-protein interactions but tend not to enter cells. We systematically compare cell permeability for 8-12 residue model peptides with helix-inducing lactam/hydrocarbon linkers between amino acid sidechains. Cell uptake increases when hydrophobic residues and lactam linkers (i, i + 4) form a contiguous hydrophobic surface patch. Uptake increases further when both hydrophobic and positively charged (but not neutral or negative) residues are clustered into like surface patches. Amphipathicity alone is however insufficient for cell uptake of acyclic sequences. Changing the linker from lactam to hydrocarbon further increases uptake, but also promotes cell lysis. Helicity, positive charge and amphipathicity together promote cell permeability. Most known bioactive helical peptides do not optimally cluster residues for amphipathicity and so are likely unoptimised for cell uptake.

Glucagon-like peptide (GLP-1) is an endogenous hormone that induces insulin secretion from pancreatic islets and modified forms are used to treat diabetes mellitus type 2. Understanding how GLP-1 interacts with its receptor (GLP-1R) can potentially lead to more effective drugs. Modeling and NMR studies of the N-terminus of GLP-1 suggest a β-turn between residues Glu9-Phe12 and a kinked alpha helix between Val16-Gly37. N-terminal turn constraints attenuated binding affinity and activity (compounds 1-8). Lys-Asp (i, i+4) crosslinks in the middle and at the C-terminus increased alpha helicity and cAMP stimulation without much effect on binding affinity or beta-arrestin 2 recruitment (compounds 9-18). Strategic positioning of helix-inducing constraints and amino acid substitutions (Tyr16, Ala22) increased peptide helicity and produced ten-fold higher cAMP potency (compounds 19-28) over GLP-1(7-37)-NH 2 . The most potent cAMP activator (compound 23) was also the most potent inducer of insulin secretion., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Protein-protein interactions mediate most physiological and disease processes. Helix-constrained peptides potently mimic or inhibit these interactions by making multiple contacts over large surface areas. However, despite high affinities, they typically have short lifetimes bound to the protein. Here we insert both a helix-inducing constraint and an adjacent electrophile into the native peptide ligand BIM to target the oncogenic protein Bcl2A1. The modified BIM peptide bonds covalently and irreversibly to one cysteine within the helix-binding groove of Bcl2A1, but not to two other exposed cysteines on its surface, and shows no covalent bonding to other Bcl2 proteins. It also penetrates cell membranes and bonds covalently to Bcl2A1 inside cells. This innovative approach to increasing receptor residence time of helical peptides demonstrates the potential to selectively silence a PPI inside cells, with selectivity over other nucleophilic sites on proteins.

The transcription factor p53 has a tumor suppressor role in leading damaged cells to apoptosis. Its activity is regulated/inhibited in healthy cells by the proteins MDM2 and MDMX. Overexpression of MDM2 and/or MDMX in cancer cells inactivates p53, facilitating tumor development. A 12-mer dual inhibitor peptide (pDI) was previously reported to be able to target and inhibit MDMX:p53 and MDM2:p53 interactions with nanomolar potency in vitro. With the aim of improving its cellular inhibitory activity, we produced a series of constrained pDI analogs featuring lactam staples that stabilize the bioactive helical conformation and fused them with a cell-penetrating peptide to increase cytosol delivery. We compared pDI and its analogs on their inhibitory potency, toxicity, and ability to enter cancer cells. Overall, the results show that these analogs keep their nanomolar affinity for MDM2 and MDMX and are highly active against cancer cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 853-863, 2016., (© 2016 Wiley Periodicals, Inc.)

Introduction: The association between osteoarthritis (OA) and obesity can lead to a reduced functional capacity, compromising the quality of life (QoL) of the elderly., Objective: To compare the functional capacity and QoL of obese and non-obese older adults with knee OA., Methods: The sample consisted of 35 subjects with OA divided into two groups, obese and non-obese subjects, according to their body mass index. To assess functional capacity, performance tests such as Timed Up and Go (TUG), gait speed test, and the six-minute walk test (6 MWT) were carried out. To assess QoL, WOMAC and SF-36 questionnaires were administered. We performed descriptive and inferential statistics using SPSS software version 20.0., Results: Elderly patients with OA were divided into two groups (obese, n=16; non-obese, n=19). Socio-demographic characteristics were similar between groups (p>0.05). The obese group showed a worst performance in TUG, brisk walking speed and 6 MWT. A more severe pain was found in the following items: "performing heavy housework chores", "going down stairs", "bending to floor" and "getting up from bed" in the obese group (p<0.05). In addition, the obese group had more difficulty to perform tasks for the following items: "going down stairs", "rising from a chair", "standing" and "getting on/off toilet" (p<0.05). There was no statistically significant difference in the assessed domains of SF-36 between groups (p>0.05)., Conclusion: OA associated with obesity caused a negative impact on functional capacity; however, quality of life scores were low, and no difference in obese and non-obese subjects was found., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

Helix-constrained polypeptides have attracted great interest for modulating protein-protein interactions (PPI). It is not known which are the most effective helix-inducing strategies for designing PPI agonists/antagonists. Cyclization linkers (X1-X5) were compared here, using circular dichroism and 2D NMR spectroscopy, for α-helix induction in simple model pentapeptides, Ac-cyclo(1,5)-[X1-Ala-Ala-Ala-X5]-NH2, in water. In this very stringent test of helix induction, a Lys1→Asp5 lactam linker conferred greatest α-helicity, hydrocarbon and triazole linkers induced a mix of α- and 3₁₀-helicity, while thio- and dithioether linkers produced less helicity. The lactam-linked cyclic pentapeptide was also the most effective α-helix nucleator attached to a 13-residue model peptide., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Poor oral availability and susceptibility to reduction and protease degradation is a major hurdle in peptide drug development. However, drugable receptors in the gut present an attractive niche for peptide therapeutics. Here we demonstrate, in a mouse model of chronic abdominal pain, that oxytocin receptors are significantly upregulated in nociceptors innervating the colon. Correspondingly, we develop chemical strategies to engineer non-reducible and therefore more stable oxytocin analogues. Chemoselective selenide macrocyclization yields stabilized analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives reveals that oxytocin has a pre-organized structure in solution, in marked contrast to earlier X-ray crystallography studies. Finally, we show that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity. Our findings have potentially important implications for clinical use of oxytocin analogues and disulphide-rich peptides in general.

Vicinal disulfide bridges, in which a disulfide bond is formed between adjacent cysteine residues, constitute an unusual but expanding class of potential allosteric disulfides. Although vicinal disulfide rings (VDRs) are relatively uncommon, they have proven to be functionally critical in almost all proteins in which they have been discovered. However, it has proved difficult to test whether these sterically constrained disulfides participate in functionally important redox transformations. We demonstrate that chemical replacement of VDRs with dicarba or diselenide bridges can be used to assess whether VDRs function as allosteric disulfides. Our approach leads to the hypothesis that not all VDRs participate in functionally important redox reactions.

Emphysema is a disease of the lung parenchyma with progressive alveolar tissue destruction that leads to peripheral airspace enlargement. In this review, we discuss how mechanical forces can contribute to disease progression at various length scales. Airspace enlargement requires mechanical failure of alveolar walls. Because the lung tissue is under a pre-existing tensile stress, called prestress, the failure of a single wall results in a redistribution of the local prestress. During this process, the prestress increases on neighboring alveolar walls which in turn increases the probability that these walls also undergo mechanical failure. There are several mechanisms that can contribute to this increased probability: exceeding the failure threshold of the ECM, triggering local mechanotransduction to release enzymes, altering enzymatic reactions on ECM molecules. Next, we specifically discuss recent findings that stretching of elastin induces an increase in the binding off rate of elastase to elastin as well as unfolds hidden binding sites along the fiber. We argue that these events can initiate a positive feedback loop which generates slow avalanches of breakdown that eventually give rise to the relentless progression of emphysema. We propose that combining modeling at various length scales with corresponding biological assays, imaging and mechanics data will provide new insight into the progressive nature of emphysema. Such approaches will have the potential to contribute to resolving many of the outstanding issues which in turn may lead to the amelioration or perhaps the treatment of emphysema in the future., (Copyright © 2011. Published by Elsevier Ltd.)

Purpose: To assess the viability of McFarlane skin flaps in rats with administration of sildenafil., Methods: Twenty Wistar rats were distributed into two groups: Control (dorsal skin flap, subdermal application of saline solution at 0.9%) and Study (dorsal skin flap, subdermal application of sildenafil). Seven days after the surgery, flaps were photographed and graphically rendered. Then, they were analyzed with AutoCAD software. Three biopsies (proximal, medial and distal) of each flap were collected for histological analysis., Results: Macroscopic analysis showed that animals of the study group had greater necrotic areas (p=0.003) in the dorsal skin flaps. Additionally, histological analysis of the distal third of these flaps showed a tendency to less granulated tissue formation in animals treated with sildenafil., Conclusion: Sildenafil subdermally was associated with lower viability of the random skin flap in rats.

Disulfide bond engineering is an important approach to improve the metabolic half-life of cysteine-containing peptides. Eleven analogues of oxytocin were synthesized including disulfide bond replacements by thioether, selenylsulfide, diselenide, and ditelluride bridges, and their stabilities in human plasma and activity at the human oxytocin receptor were assessed. The cystathionine (K(i) = 1.5 nM, and EC₅₀ = 32 nM), selenylsulfide (K(i) = 0.29/0.72 nM, and EC₅₀ = 2.6/154 nM), diselenide (K(i) = 11.8 nM, and EC₅₀ = 18 nM), and ditelluride analogues (K(i) = 7.6 nM, and EC₅₀ = 27.3 nM) retained considerable affinity and functional potency as compared to oxytocin (K(i) = 0.79 nM, and EC₅₀ = 15 nM), while shortening the disulfide bridge abolished binding and functional activity. The mimetics showed a 1.5-3-fold enhancement of plasma stability as compared to oxytocin (t(½) = 12 h). By contrast, the all-D-oxytocin and head to tail cyclic oxytocin analogues, while significantly more stable with half-lives greater than 48 h, had little or no detectable binding or functional activity.

Many fundamental cellular and extracellular processes in the body are mediated by enzymes. At the single molecule level, enzyme activity is influenced by mechanical forces. However, the effects of mechanical forces on the kinetics of enzymatic reactions in complex tissues with intact extracellular matrix (ECM) have not been identified. Here we report that physiologically relevant macroscopic mechanical forces modify enzyme activity at the molecular level in the ECM of the lung parenchyma. Porcine pancreatic elastase (PPE), which binds to and digests elastin, was fluorescently conjugated (f-PPE) and fluorescent recovery after photobleach was used to evaluate the binding kinetics of f-PPE in the alveolar walls of normal mouse lungs. Fluorescent recovery after photobleach indicated that the dissociation rate constant (k(off)) for f-PPE was significantly larger in stretched than in relaxed alveolar walls with a linear relation between k(off) and macroscopic strain. Using a network model of the parenchyma, a linear relation was also found between k(off) and microscopic strain on elastin fibers. Further, the binding pattern of f-PPE suggested that binding sites on elastin unfold with strain. The increased overall reaction rate also resulted in stronger structural breakdown at the level of alveolar walls, as well as accelerated decay of stiffness and decreased failure stress of the ECM at the macroscopic scale. These results suggest an important role for the coupling between mechanical forces and enzyme activity in ECM breakdown and remodeling in development, and during diseases such as pulmonary emphysema or vascular aneurysm. Our findings may also have broader implications because in vivo, enzyme activity in nearly all cellular and extracellular processes takes place in the presence of mechanical forces., (Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.)