Reduced Amino Acid Specificity of Mammalian Tyrosyl-tRNA Synthetase is Associated with Elevated Mistranslation of Tyr Codons

Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, no significant change in cellular viability was observed. Monitoring of Phe and Tyr levels revealed that changes in error rates correlated with changes in amino acid pools, suggesting that mischarging of tRNATyr with noncognate Phe by tyrosyl-tRNA synthetase was responsible for mistranslation. Steady-state kinetic analyses of CHO cytoplasmic tyrosyl-tRNA synthetase revealed a 25-fold lower specificity for Tyr over Phe as compared with previously characterized bacterial enzymes, consistent with the observed increase in translation error rates during tyrosine limitation. Functional comparisons of mammalian and bacterial tyrosyl-tRNA synthetase revealed key differences at residues responsible for amino acid recognition, highlighting differences in evolutionary constraints for translation quality control

AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy

The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman\u27s reproductive lifespan, resulting in menopause. Mullerian inhibiting substance (MIS) (or anti-Mullerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice. The ovaries of MIS-treated mice were smaller than those in controls and did not contain growing follicles but retained a normal ovarian reserve. When mice treated with AAV9/MIS were paired with male breeders, they exhibited complete and permanent contraception for their entire reproductive lifespan, disrupted vaginal cycling, and hypergonadotropic hypogonadism. However, when ovaries from AAV9-MIS-treated mice were transplanted orthotopically into normal recipient mice, or when treatment with the protein was discontinued, folliculogenesis resumed, suggesting reversibility. One of the important causes of primary ovarian insufficiency is chemotherapy-induced primordial follicle depletion, which has been proposed to be mediated in part by increased activation. To test the hypothesis that MIS could prevent chemotherapy-induced overactivation, mice were given carboplatin, doxorubicin, or cyclophosphamide and were cotreated with AAV9-MIS, recombinant MIS protein, or vehicle controls. We found significantly more primordial follicles in MIS-treated animals than in controls. Thus treatment with MIS may provide a method of contraception with the unique characteristic of blocking primordial follicle activation that could be exploited to prevent the primary ovarian insufficiency often associated with chemotherapy

PRODUÇÃO E QUALIDADE DE FRUTOS DE ERVILHA TORTA

O objetivo deste trabalho foi avaliar a influência de doses de potássio em cobertura na produção e na qualidade de ervilha, cultivar Torta de Flor Roxa. O experimento foi conduzido no período de março a julho de 2006, em blocos casualizados, com seis repetições e seis tratamentos: 0,0; 1,14; 2,34; 3,54; 4,68; 5,88 g planta-1 de K2O aplicados em cobertura a partir do florescimento. Não houve aumento na produção (com média de 29,34 vagens comerciais e 7,37 g por planta) de ervilha torta e também não foi alterada a qualidade dos frutos com o aumento das doses de K2O fornecidas, provavelmente pelo solo já apresentar teor alto deste nutriente (5,7mmolc dm3). Apesar de ser recomendado a aplicação de potássio em cobertura, conclui-se que as doses aplicadas não influenciaram a produção nem qualidade dos frutos de ervilha torta

Uso da técnica de tomografia computadorizada cone Beam modificada para avaliação padronizada dos tecidos ósseo e gengival em implantodontia/ Use of the modified cone beam computed tomography technique for standardized assessment of Bone and gingival tissues in implant dentistry

Este estudo avaliou as dimensões da unidade dentogengival pré-operatória e mudanças nos tecidos ósseo e gengival na reabilitação com implante imediato pela técnica Soft Tissue Cone-Beam Computed Tomography (ST-CBCT). Trata-se de uma série de seis pacientes submetidos à reabilitação com implante imediato em área estética da maxila. Realizou-se as seguintes medidas no pré e no pós-operatório de 03 e 06 meses: Espessura do Osso Vestibular (EO), Distância da Crista Óssea Vestibular à Junção Amelocementária ou à coroa protética (AO), Distância da Crista Óssea Vestibular à Plataforma do Implante (AO), Espessura de Tecido Mole (EG) e Distância da Margem Gengival à Crista Óssea Vestibular (AG), submetidas à estatística descritiva (média e desvio-padrão). A EO aumentou nos pacientes 01 (1,03mm), 02 (0,66mm) e 06 (0,06mm) e reduziu nos pacientes 03 (0,17mm), 04 (0,41mm) e 05 (0,38mm). Nos pacientes 02 e 03 o osso vestibular estava no nível da plataforma do implante; nos demais pacientes os implantes permaneceram infra-ósseos. A EG aumentou nos pacientes 01 (0,30mm), 02 (0,80mm), 03 (1,27mm) e 06 (0,74mm) e houve redução na altura gengival dos pacientes 01 (-0,30mm), 03 (-0,04mm) e 05 (0,06mm). Houve divergência na classificação do biótipo gengival nos pacientes 03 e 05. A técnica ST-CBCT demonstrou ser um instrumento não invasivo valioso para avaliação dos tecidos ósseo e gengival no pré e pós-operatório de reabilitação com implantes imediatos e permitiu mensuração padronizada dos tecidos periimplantares a longo prazo

The Evolution of Primate Short-Term Memory.

Short-term memory is implicated in a range of cognitive abilities and is critical for understanding primate cognitive evolution. To investigate the effects of phylogeny, ecology and sociality on short-term memory, we tested the largest and most diverse primate sample to date (421 non-human primates across 41 species) in an experimental delayed-response task. Our results confirm previous findings that longer delays decrease memory performance across species and taxa. Our analyses demonstrate a considerable contribution of phylogeny over ecological and social factors on the distribution of short-term memory performance in primates; closely related species had more similar short-term memory abilities. Overall, individuals in the branch of Hominoidea performed better compared to Cercopithecoidea, who in turn performed above Platyrrhini and Strepsirrhini. Interdependencies between phylogeny and socioecology of a given species presented an obstacle to disentangling the effects of each of these factors on the evolution of short-term memory capacity. However, this study offers an important step forward in understanding the interspecies and individual variation in short-term memory ability by providing the first phylogenetic reconstruction of this trait’s evolutionary history. The dataset constitutes a unique resource for studying the evolution of primate cognition and the role of short-term memory in other cognitive abilities.info:eu-repo/semantics/publishedVersio

Establishing an infrastructure for collaboration in primate cognition research

Inferring the evolutionary history of cognitive abilities requires large and diverse samples. However, such samples are often beyond the reach of individual researchers or institutions, and studies are often limited to small numbers of species. Consequently, methodological and site-specific-differences across studies can limit comparisons between species. Here we introduce the ManyPrimates project, which addresses these challenges by providing a large-scale collaborative framework for comparative studies in primate cognition. To demonstrate the viability of the project we conducted a case study of short-term memory. In this initial study, we were able to include 176 individuals from 12 primate species housed at 11 sites across Africa, Asia, North America and Europe. All subjects were tested in a delayed-response task using consistent methodology across sites. Individuals could access food rewards by remembering the position of the hidden reward after a 0, 15, or 30-second delay. Overall, individuals performed better with shorter delays, as predicted by previous studies. Phylogenetic analysis revealed a strong phylogenetic signal for short-term memory. Although, with only 12 species, the validity of this analysis is limited, our initial results demonstrate the feasibility of a large, collaborative open-science project. We present the ManyPrimates project as an exciting opportunity to address open questions in primate cognition and behaviour with large, diverse datasets

Establishing an infrastructure for collaboration in primate cognition research

Inferring the evolutionary history of cognitive abilities requires large and diverse samples. However, such samples are often beyond the reach of individual researchers or institutions, and studies are often limited to small numbers of species. Consequently, methodological and site-specific-differences across studies can limit comparisons between species. Here we introduce the ManyPrimates project, which addresses these challenges by providing a large-scale collaborative framework for comparative studies in primate cognition. To demonstrate the viability of the project we conducted a case study of short-term memory. In this initial study, we were able to include 176 individuals from 12 primate species housed at 11 sites across Africa, Asia, North America and Europe. All subjects were tested in a delayed-response task using consistent methodology across sites. Individuals could access food rewards by remembering the position of the hidden reward after a 0, 15, or 30-second delay. Overall, individuals performed better with shorter delays, as predicted by previous studies. Phylogenetic analysis revealed a strong phylogenetic signal for short-term memory. Although, with only 12 species, the validity of this analysis is limited, our initial results demonstrate the feasibility of a large, collaborative open-science project. We present the ManyPrimates project as an exciting opportunity to address open questions in primate cognition and behaviour with large, diverse datasets

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly