Impact of the chemical modification of tRNAs anticodon loop on the variability and evolution of codon usage in proteobacteria.

Despite the highly conserved nature of the genetic code, the frequency of usage of each codon can vary significantly. The evolution of codon usage is shaped by two main evolutionary forces: mutational bias and selection pressures. These pressures can be driven by environmental factors, but also by the need for efficient translation, which depends heavily on the concentration of transfer RNAs (tRNAs) within the cell. The data presented here supports the proposal that tRNA modifications play a key role in shaping the overall preference of codon usage in proteobacteria. Interestingly, some codons, such as CGA and AGG (encoding arginine), exhibit a surprisingly low level of variation in their frequency of usage, even across genomes with differing GC content. These findings suggest that the evolution of GC content in proteobacterial genomes might be primarily driven by changes in the usage of a specific subset of codons, whose usage is itself influenced by tRNA modifications.

Codon usage bias in yeasts and its correlation with gene expression, growth temperature, and protein structure.

Codon usage bias (CUB) has been described in viruses, prokaryotes, and eukaryotes and has been linked to several cellular and environmental factors, such as the organism's growth temperature, gene expression levels, and regulation of protein synthesis and folding. Most of the studies in this area have been conducted in bacteria and higher eukaryotes, in some cases with different results. In this study, a comparative analysis of CUB in yeasts isolated from cold and template environments was performed in order to evaluate the correlation of CUB with yeast optimal temperature of growth (OTG), gene expression levels, cellular function, and structure of encoded proteins. Among the main findings, highly expressed ORFs tend to have a more similar CUB within and between yeasts, and a direct correlation between codons ending in C and expression level was generally found. A low correspondence between CUB and OTG was observed, with an inverse correlation for some codons ending in C. The clustering of yeasts based on their CUB partially aligns with their OTG, being more consistent for yeasts with lower OTG. In most yeasts, the abundance of preferred codons was generally lower at the 5' end of ORFs, higher in segments encoding beta strand, lower in segments encoding extracellular and transmembrane regions, and higher in "translation" and "energy metabolism" pathways, especially in highly expressed ORFs. Based on our findings, it is suggested that the abundance and distribution of preferred and non-preferred codons along mRNAs contribute to proper protein folding and functionality by regulating protein synthesis rates, becoming a more important factor under conditions that require faster protein synthesis in yeasts.

MicroRNA Transcriptomes Reveal Prevalence of Rare and Species-Specific Arm Switching Events During Zebrafish Ontogenesis.

In metazoans, microRNAs (miRNAs) are essential regulators of gene expression, affecting critical cellular processes from differentiation and proliferation, to homeostasis. During miRNA biogenesis, the miRNA strand that loads onto the RNA-induced Silencing Complex (RISC) can vary, leading to changes in gene targeting and modulation of biological pathways. To investigate the impact of these "arm switching" events on gene regulation, we analyzed a diverse range of tissues and developmental stages in zebrafish by comparing 5p and 3p arms accumulation dynamics between embryonic developmental stages, adult tissues, and sexes. We also compared variable arm usage patterns observed in zebrafish to other vertebrates including arm switching data from fish, birds, and mammals. Our comprehensive analysis revealed that variable arm usage events predominantly take place during embryonic development. It is also noteworthy that isomiR occurrence correlates to changes in arm selection evidencing an important role of microRNA distinct isoforms in reinforcing and modifying gene regulation by promoting dynamics switches on miRNA 5p and 3p arms accumulation. Our results shed new light on the emergence and coordination of gene expression regulation and pave the way for future investigations in this field.

Speech pauses in speakers with and without aphasia: A usage-based approach.

Pauses in speech are indicators of cognitive effort during language production and have been examined to inform theories of lexical, grammatical and discourse processing in healthy speakers and individuals with aphasia (IWA). Studies of pauses have commonly focused on their location and duration in relation to grammatical properties such as word class or phrase complexity. However, recent studies of speech output in aphasia have revealed that utterances of IWA are characterised by stronger collocations, i.e., combinations of words that are often used together. We investigated the effects of collocation strength and lexical frequency on pause duration in comic strip narrations of IWA and non-brain-damaged (NBD) individuals with part of speech (PoS; content and function words) as covariate. Both groups showed a decrease in pause duration within more strongly collocated bigrams and before more frequent content words, with stronger effects in IWA. These results are consistent with frameworks which propose that strong collocations are more likely to be processed as holistic, perhaps even word-like, units. Usage-based approaches prove valuable in explaining patterns of preservation and impairment in aphasic language production.

Parental executive functions and motivations unveil variations in young children's screen media use.

BACKGROUND: The increased screen media use among children aged 3 to 5, particularly in the post-COVID era, is concerning. Despite several organizations' recommendation of a one-hour screen limit for young children, actual usage often exceeds this guideline. OBJECTIVE: This study explored the influence of parental characteristics such as self-efficacy, motivation, socioeconomic status, and cognitive abilities on children's screen time habits. METHODS: Employing a feature selection model, 251 caregivers answered an online survey, presenting data from themselves and on-screen usage for 126 girls and 125 boys. We found that the caregiver's executive functions, including cognitive flexibility, initiation, task monitoring, and material organization, significantly impact children's screen time. RESULTS: Our analysis highlighted the vital role of caregivers' self-efficacy in moderating children's screen usage. Family net income, children's age and gender, and motivations related to children's desires and behavioral control were also significant contributors to usage patterns. CONCLUSION: This study offers insights into interventions and effective parenting strategies in the digital age, highlighting the importance of addressing socio-demographic factors in understanding this complex issue.

Non-Canonical Aspects of Antibiotics and Antibiotic Resistance.

The understanding of antibiotic resistance, one of the major health threats of our time, is mostly based on dated and incomplete notions, especially in clinical contexts. The "canonical" mechanisms of action and pharmacodynamics of antibiotics, as well as the methods used to assess their activity upon bacteria, have not changed in decades; the same applies to the definition, acquisition, selective pressures, and drivers of resistance. As a consequence, the strategies to improve antibiotic usage and overcome resistance have ultimately failed. This review gathers most of the "non-canonical" notions on antibiotics and resistance: from the alternative mechanisms of action of antibiotics and the limitations of susceptibility testing to the wide variety of selective pressures, lateral gene transfer mechanisms, ubiquity, and societal factors maintaining resistance. Only by having a "big picture" view of the problem can adequate strategies to harness resistance be devised. These strategies must be global, addressing the many aspects that drive the increasing prevalence of resistant bacteria aside from the clinical use of antibiotics.

Selective and non-selective evolutionary signatures found in the simplest replicative biological entities.

Mitoviruses, which are considered evolutionary relics of extinct alpha-proteobacteria RNA phages, represent one of the simplest self-replicating biological systems. This study aims to quantitatively describe genomes and identify potential genomic signatures that support the protein phylogenetic-based classification criterion. Genomic variables, such as mononucleotide and dinucleotide composition, codon usage bias, and minimal free energy derived from optimized predicted RNA secondary structure, were analyzed. From the values obtained, the main evolutionary pressures were discussed, indicating that natural selection plays a significant role in shaping mitovirus genomes. However, neutral evolution also makes a significant contribution. This study reveals a significant discovery of structural divergence in Kvaramitovirus. The energy minimization approach employed to study 2D folding in this study reveals a distinct spatial organization of their genomes, providing evidence for the hypothesis of a single evolutionary event of circularization in the most recent common ancestor of the lineage. This hypothesis was discussed in light of recent discoveries by other researchers that partially support the existence of mitoviruses with circular genomes. Finally, this study represents a significant advancement in the understanding of mitoviruses, as it quantitatively describes the nucleotide sequence at the family and genus taxonomic levels. Additionally, we provide hypotheses that can be experimentally validated to inspire new research and address the gaps in knowledge of this fascinating, basally divergent RNA virus lineage.

Profile of sexually transmitted infections among attendees of special clinics (Suraksha) at an apex regional sexually transmitted disease centre in North India ­ a five-year study

Introduction: Sexually transmitted infections (STIs) present significant global and national health challenges, particularly in India. Objective: To estimate the prevalence and characteristics of STIs among attendees at the Suraksha Clinic in the Apex Regional STD Centre, Safdarjung Hospital. Methods:Retrospective data from January 2018 to December 2022 were statistically analyzed using Excel and SPSS. The study included the examination for diagnosis of various STIs, such as syphilis, human immunodeficiency virus (HIV), gonorrhoea, chlamydiasis, trichomoniasis, candidiasis, bacterial vaginosis, chancroid, and genital herpes. Gender distribution and syndromic diagnoses, including vaginal/cervical discharge and genital ulcers, were also considered. Referrals to Integrated Counseling and Testing Centres for HIV testing were analyzed. Results: The outcomes reveal a substantial burden of STIs, with 3.06% showing reactivity to syphilis, 1.74% testing positive for HIV, 3.36% for gonorrhoea, 11.78% for chlamydiasis, 1.05% for trichomoniasis, 26.24% for candidiasis, 9.97% for bacterial vaginosis, 7.80% for chancroid, 11.64% for herpes genitalis, and 4.01% for other non-STIs. Attendees' interactions included 34.36% of referrals to Integrated Counseling and Testing Centres for HIV testing. The gender distribution showed 58.92% male and 40.94% female attendees. Conclusion: Syndromic diagnoses, including vaginal/cervical discharge (21.22%) and genital warts (8.00%), highlight prevalent conditions, necessitating routine screening, early detection, and targeted interventions for effective disease control and prevention. These findings underscore the significance of integrated screening, patient education, and proactive strategies to safeguard public health in the face of rising STI rates. (AU)

Introdução: As infecções sexualmente transmissíveis (IST) apresentam desafios de saúde globais e nacionais significativos, particularmente na Índia. Objetivo: Estimar a prevalência e as características das IST entre os pacientes atendidos na Clínica Suraksha do Centro Regional de doenças sexualmente transmissíveis (DST) Apex, Hospital Safdarjung. Métodos: Dados retrospectivos de janeiro de 2018 a dezembro de 2022 foram analisados estatisticamente utilizando Excel e Statistical Package for the Social Sciences (SPSS). O estudo inclui o exame para diagnóstico de diversas IST, como sífilis, HIV, gonorreia, clamídia, tricomoníase, candidíase, vaginose bacteriana, cancroide e herpes genital. A distribuição por gênero e os diagnósticos sindrômicos, incluindo corrimento vaginal/cervical e úlceras genitais, também foram considerados. Foram analisados encaminhamentos para Centros Integrados de Aconselhamento e Testagem para testagem de HIV. Resultados: Os resultados revelam uma carga substancial de IST, com 3,06% apresentando reatividade à sífilis, 1,74% testando positivo para HIV, 3,36% para gonorreia, 11,78% para clamídia, 1,05% para tricomoníase, 26,24% para candidíase, 9,97% para vaginose bacteriana, 7,80% para cancroide, 11,64% para herpes genital e 4,01% para outras infecções não IST. As interações dos participantes incluíram 34,36% de encaminhamentos para Centros Integrados de Aconselhamento e Testagem para testes de HIV. A distribuição por gênero mostrou 58,92% de participantes do sexo masculino e 40,94% do sexo feminino. Conclusão: Os diagnósticos sindrômicos, incluindo corrimento vaginal/cervical (21,22%) e verrugas genitais (8,00%), destacam condições prevalentes, necessitando de exames de rotina, detecção precoce e intervenções direcionadas para controle e prevenção eficazes de doenças. Estas conclusões sublinham a importância do rastreio integrado, da educação dos pacientes e de estratégias proativas para salvaguardar a saúde pública diante do aumento das taxas de IST. (AU)

A roadmap for developing Venezuelan equine encephalitis virus (VEEV) vaccines: Lessons from the past, strategies for the future.

Venezuelan equine encephalitis (VEE) is a zoonotic infectious disease caused by the Venezuelan equine encephalitis virus (VEEV), which can lead to severe central nervous system infections in both humans and animals. At present, the medical community does not possess a viable means of addressing VEE, rendering the prevention of the virus a matter of paramount importance. Regarding the prevention and control of VEEV, the implementation of a vaccination program has been recognized as the most efficient strategy. Nevertheless, there are currently no licensed vaccines or drugs available for human use against VEEV. This imperative has led to a surge of interest in vaccine research, with VEEV being a prime focus for researchers in the field. In this paper, we initially present a comprehensive overview of the current taxonomic classification of VEEV and the cellular infection mechanism of the virus. Subsequently, we provide a detailed introduction of the prominent VEEV vaccine types presently available, including inactivated vaccines, live attenuated vaccines, nucleic acid, and virus-like particle vaccines. Moreover, we emphasize the challenges that current VEEV vaccine development faces and suggest urgent measures that must be taken to overcome these obstacles. Notably, based on our latest research, we propose the feasibility of incorporation codon usage bias strategies to create the novel VEEV vaccine. Finally, we prose several areas that future VEEV vaccine development should focus on. Our objective is to encourage collaboration between the medical and veterinary communities, expedite the translation of existing vaccines from laboratory to clinical applications, while also preparing for future outbreaks of new VEEV variants.

Innovative perspectives in limbic surgery using deep brain stimulation.

Limbic surgery is one of the most attractive and retaken fields of functional neurosurgery in the last two decades. Psychiatric surgery emerged from the incipient work of Moniz and Lima lesioning the prefrontal cortex in agitated patients. Since the onset of stereotactic and functional neurosurgery with Spiegel and Wycis, the treatment of mental diseases gave attention to refractory illnesses mainly with the use of thalamotomies. Neurosis and some psychotic symptoms were treated by them. Several indications when lesioning the brain were included: obsessive-compulsive disorder, depression, and aggressiveness among others with a diversity of targets. The indiscriminately use of anatomical sites without enough scientific evidence, and uncertainly defined criteria for selecting patients merged with a deficiency in ethical aspects, brought a lack of procedures for a long time: only select clinics allowed this surgery around the world from 1950 to the 1990s. In 1999, Nuttin et al. began a new chapter in limbic surgery with the use of Deep Brain Stimulation, based on the experience of pain, Parkinson's disease, and epilepsy. The efforts were focused on different targets to treat depression and obsessive-compulsive disorders. Nevertheless, other diseases were added to use neuromodulation. The goal of this article is to show the new opportunities to treat neuropsychiatric diseases.

Technology acceptance factors of e-commerce among young people: An integration of the technology acceptance model and theory of planned behavior.

This study aims to examine the factors involved in the technological acceptance of e-commerce among young university students. The research is focused on the articulation between the Technology Acceptance Model (TAM) and the Theory of Planned Behavior (TPB) by collecting secondary data and conducting a survey with 376 young university students, validated by using structural equations (SEM). The predominant factors and variables involved in the adoption of e-commerce by young university students in Medellín were identified. The results show that the attitude towards usage has a positive effect on usage intention because people consider a website to be useful and trust builds regarding usage intention, which will enable to make the transaction in an easier and safer way. In conclusion, perceived usefulness comes before attitude towards usage, and thus the main direct antecedent of the intention to use e-commerce is established.

Codon usage bias of Venezuelan equine encephalitis virus and its host adaption.

Venezuelan equine encephalitis virus (VEEV) is an emerging zoonotic virus in the alphavirus genus. It can be transmitted to humans due to spillover from equid-mosquito cycles. The symptoms caused by VEEV include fever, headache, myalgia, nausea, and vomiting. It can also cause encephalitis in severe cases. The evolutionary features of VEEV are largely unknown. In this study, we comprehensively analyzed the codon usage pattern of VEEV by computing a variety of indicators, such as effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), on 130 VEEV coding sequences retrieved from GenBank. The results showed that the codon usage bias of VEEV is relatively low. ENc-GC3s plot, neutrality plot, and CAI-ENc correlation analyses supported that translational selection plays an important role in shaping the codon usage pattern of VEEV whereas the mutation pressure has a minor influence. Analysis of RSCU values showed that most of the preferred codons in VEEV are C/G-ended. Analysis of dinucleotide composition found that all CG- and UA-containing codons are not preferentially used. Phylogenetic analysis showed that VEEV isolates can be clustered into three genera and evolutionary force affects the codon usage pattern. Furthermore, a correspondence analysis (COA) showed that aromaticity and hydrophobicity as well as geographical distribution also have certain effects on the codon usage variation of VEEV, suggesting the possible involvement of translational selection. Overall, the codon usage of VEEV is comparatively slight and translational selection might be the main factor that shapes the codon usage pattern of VEEV. This study will promote our understanding about the evolution of VEEV and its host adaption, and might provide some clues for preventing the cross-species transmission of VEEV.

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer / Estudo estequioproteômico de proteínas e vias expressas diferencialmente no câncer de cabeça e pescoço

Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.(AU)

A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.(AU)

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer / Estudo estequioproteômico de proteínas e vias expressas diferencialmente no câncer de cabeça e pescoço

Abstract Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

Resumo A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.

Implications of deficit discourse in the conversations of a mother who requests forced treatment / Implicações do discurso do déficit nas conversas de uma mãe que solicita tratamento forçado / Implications du discours déficitaire sur les conversations d'une mère qui demande traitement forcé / Implicaciones del discurso del déficit en las conversaciones de una madre que solicita tratamiento forzado

Abstract This case study analyzes the implications of deficit discourse on the daily conversations of a mother who requested forced treatment for her son. Data were analyzed drawing on social construction, with an emphasis on positioning theory and deficit discourse. Two episodes displaying deficit discourse were analyzed: one about the son as someone who is powerless, coping with drug use and another about the mother as someone unable to help her son. A sample letter was constructed using relational discourse, which provided new understandings for practice. Results support the benefits of collaborative and relational approaches for people who use drugs and for the emotional support of families.

Resumo Este estudo de caso analisa as implicações do discurso do déficit nas conversas cotidianas de uma mãe que solicitou tratamento forçado para seu filho. Os dados foram analisados a partir da construção social, com ênfase na teoria do posicionamento e do discurso do déficit. Dois episódios foram analisados a partir do discurso do déficit: um sobre o filho como alguém que é impotente no enfrentamento do uso de drogas e outro sobre a mãe como alguém incapaz de ajudar seu filho. Foi construída uma carta ilustrativa a partir do discurso relacional, que proporcionou novos entendimentos para a prática. Os resultados corroboram os benefícios das abordagens colaborativas e relacionais para o suporte emocional de pessoas que usam drogas e suas famílias.

Résumé Cette étude de cas analyse les implications du discours déficitaire sur les conversations quotidiennes d'une mère qui a demandé traitement forcé pour son fils. Les données ont été analysées en s'appuyant sur la construction sociale, en mettant l'accent sur la théorie du positionnement et le discours déficitaire. Deux épisodes ont été analyses utilisant le discours déficitaire: l'un sur le fils en tant que personne impuissante face à l'usage de drogue, et l'autre sur la mère en tant que personne incapable d'aider son fils. Une lettre illustrative a été construit utilisant le discours relationnel, qui a fourni de nouvelles compréhensions pour la pratique. Les résultats confirment les avantages des approches collaboratives et relationnelles pour le soutien émotionnel des personnes qui consomment des drogues et leurs familles.

Resumen Este estudio de caso analiza las implicaciones del discurso del déficit en las conversaciones diarias de una madre que solicitó tratamiento forzado para su hijo. Los datos fueron analizados a partir de la construcción social, con énfasis en la teoría del posicionamiento y el discurso del déficit. Se analizaron dos episodios a partir del discurso del déficit: uno sobre el hijo como alguien que es impotente frente al uso de drogas y otro sobre la madre como alguien incapaz de ayudar a su hijo. Se construyó una carta ilustrativa utilizando el discurso relacional, que proporcionó nuevas comprensiones para la práctica. Los resultados respaldan los beneficios de los enfoques colaborativos y relacionales para el soporte emocional de las personas que usan drogas y sus familias.

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer / Estudo estequioproteômico de proteínas e vias expressas diferencialmente no câncer de cabeça e pescoço

Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer

Abstract Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

Resumo A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.

Do funcionamento autoerótico à desfusão pulsional: um modelo teórico para a etiologia do recurso à droga na esquizofrenia / From autoerotic functioning to instinctual defusion: a theoretical model for the etiology of drug use in schizophrenia / Du fonctionnement autoérotique à la défusion pulsionnelle: un modèle théorique pour l'étiologie de l'usage de drogues dans la schizophrénie / Del funcionamiento autoerótico a la defusión pulsional: un modelo teórico para la etiologia del consumo de drogas en la esquizofenia

O artigo apresenta a construção de um modelo teórico-clínico em psicopatologia psicanalítica, acerca dos determinantes estruturais do recurso à droga na psicose e, em especial, na esquizofrenia. Partimos da tese de Lacan acerca dos efeitos de adesão ao gozo autoerótico decorrente da ruptura com o gozo fálico, que coloca o problema relativo ao estatuto dessa ruptura na toxicomania e, em especial, da função do recurso à droga sobre os efeitos desta ruptura. Nossa hipótese é que o recurso à droga obedece a uma tentativa de refusão pulsional com consequências catastróficas. Conduzimos o levantamento dos textos de Freud que se organizam em torno da economia pulsional, tanto na sua abordagem do recurso à droga, como na sua abordagem da etiologia da psicose e da função reparadora do delírio. Como resultado, obtivemos os índices estruturais para o diagnóstico do recurso à droga na psicose.

Resumos The article presents the construction of a theoretical-clinical model in psychoanalytic psychopathology about the structural determinants of drug use in psychosis and in schizophrenia. We start from Lacan's thesis about the effects of adherence to autoerotic jouissance resulting from the rupture with phallic jouissance, which poses the problem concerning the status of this rupture in drug addiction and the role of drug use on the effects of this rupture. Our hypothesis is that the use of drugs follows an attempt at instinctual refusion with catastrophic consequences. We conducted a survey of Freud's texts that are organized around the drive economy, both in his approach to the use of drugs and in his approach to the etiology of psychosis and the reparative function of delusion. As a result, we obtained the structural indices for the diagnosis of drug use in psychosis..

L'article présente la construction d'un modèle théorico-clinique, en psychopathologie psychanalytique à propos des déterminants structurels de l'usage de drogues dans la psychose et, en particulier, dans la schizophrénie. Nous partons de la thèse lacanienne sur les effets d'adhésion à la jouissance autoérotique résultant de la rupture avec la jouissance phallique, ce qui pose le problème du statut de cette rupture dans la toxicomanie et, en particulier, du rôle de l'usage de drogues sur les effets de cette rupture. Notre hypothèse est que le recours aux drogues obéit à une tentative de refusion pulsionnelle aux conséquences catastrophiques. Nous avons mené l'enquête sur les textes de Freud qui s'organisent autour de l'économie pulsionnelle, tant dans son approche de la ressource médicamenteuse que dans son approche de l'étiologie de la psychose et de la fonction réparatrice du délire. Nous avons ainsi obtenu les indices structurels pour le diagnostic de l'usage de drogues dans la psychose.

Este artículo presenta la construcción de un modelo teórico-clínico en psicopatología psicoanalítica sobre los determinantes estructurales del consumo de drogas en la psicosis y, en particular, en la esquizofrenia. Partimos de la tesis de Lacan sobre los efectos de la adhesión al goce autoerótico resultante de la ruptura con el goce fálico, que plantea el problema del estatuto de esta ruptura en la drogadicción y, en particular, el papel del consumo de drogas en los efectos de esta ruptura. Nuestra hipótesis es que el uso de drogas sigue un intento de rechazo instintivo con consecuencias catastróficas. Realizamos un recorrido por los textos de Freud que se organizan en torno a la economía pulsional, tanto en su abordaje del uso de drogas como en su abordaje de la etiología de la psicosis y de la función reparadora del delirio. Como resultado obtuvimos los índices estructurales para el diagnóstico del consumo de drogas en psicosis.

Oxidative stress strongly restricts the effect of codon choice on the efficiency of protein synthesis in Escherichia coli.

Introduction: The response of enterobacteria to oxidative stress is usually considered to be regulated by transcription factors such as OxyR and SoxR. Nevertheless, several reports have shown that under oxidative stress the levels, modification and aminoacylation of tRNAs may be altered suggesting a role of codon bias in regulation of gene expression under this condition. Methods: In order to characterize the effects of oxidative stress on translation elongation we constructed a library of 61 plasmids, each coding for the green fluorescent protein (GFP) translationally fused to a different set of four identical codons. Results: Using these reporters, we observed that GFP production levels vary widely (~15 fold) when Escherichia coli K-12 is cultured in minimal media as a consequence of codon choice variations. When bacteria are cultured under oxidative stress caused by paraquat the levels of GFP produced by most clones is reduced and, in contrast to control conditions, the range of GFP levels is restricted to a ~2 fold range. Restricting elongation of particular sequences does not increase the range of GFP production under oxidative stress, but altering translation initiation rates leads to an increase in this range. Discussion: Altogether, our results suggest that under normal conditions the speed of translation elongation is in the range of the speed of initiation and, consequently, codon choice impacts the speed of protein synthesis. In contrast, under oxidative stress translation initiation becomes much slower than elongation, limiting the speed of translation such that codon choice has at most only subtle effects on the overall output of translation.

Myths and Misconceptions around Antibiotic Resistance: Time to Get Rid of Them.

The antibiotic resistance arena is fraught with myths and misconceptions, leading to wrong strategies to combat it. It is crucial to identify them, discuss them in light of current evidence, and dispel those that are unequivocally wrong. This article proposes some concepts that may qualify as misconceptions around antibiotic resistance: the susceptible-resistant dichotomy; that incomplete antibiotic courses cause resistance; that resistance "emerges" in patients and hospitals; that antibiotics are mostly abused clinically; that resistance is higher in countries that use more antibiotics; that reducing antibiotic usage would reduce resistance; that financial incentives would "jumpstart" research and development of antibiotics; that generic and "original" antibiotics are the same; and that new anti-infective therapies are just around the corner. While some of these issues are still controversial, it is important to recognize their controversial status, instead of repeating them in specialized literature and lectures and, especially, in the planning of strategies to cope with resistance.