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Transfer RNAs (tRNAs) are central to protein synthesis, ensuring precise decoding of the genetic code by delivering aminoacids to the ribosome. Among all RNA species, tRNAs are the most heavily and diversely modified, with modifications playing critical roles in stability, folding, and function. Here, we present a comprehensive, isodecoder-level map of tRNA modifications in the human pathogen Vibrio cholerae . This map was generated by chemical-based sequencing methods, comparing wild-type and deletion strains. By assigning specific tRNA modifications to their cognate enzymes, we defined a comprehensive modification landscape in Vibrio cholerae and confirmed species-specific features, such as the presence of a functional TrmK enzyme, largely restricted to Gram-positive bacteria. Additionally, we detected a modification at U55 that occurs independently of TruB. To assess the biological significance of these modifications, we evaluated fitness under both standard conditions and subinhibitory antibiotic stress, and examined how modifications in the anticodon stem-loop region influence codon decoding efficiency and accuracy. Based on a comparative analysis of E. coli and V. cholerae , we discuss how species-specific differences in tRNA isodecoder gene repertoires may influence the functional impact and biological importance of tRNA modifications. This work provides the first experimentally validated, genome-wide map of tRNA modifications in V. cholerae , serving as a reference for future research into RNA modifications, translation regulation, and pathogen biology.

O ingresso no 1ºciclo é uma fase importante de desenvolvimento e aprendizagem dos alunos, no que respeita às competências comunicativas, sociais, emocionais e cognitivas. Todas estas competências resultam de experiências vivenciadas nos primeiros anos de vida, pelas interações com os adultos e os pares e o sucesso das suas comunicações, verificando-se uma relação entre a comunicação e o sucesso escolar. Uma vez que muitos alunos apresentam dificuldades comunicativas em idade escolar, torna-se pertinente identificar essas dificuldades, no sentido de implementar uma intervenção eficaz e atempada às necessidades dos alunos. A finalidade deste estudo exploratório consiste em analisar os resultados da Escala de Comunicação para a Idade Escolar (ECIE) – Versão para Professores (Batista, Monteiro, Dias, Azevedo, & Cruz- Santos, 2019) que contempla três dimensões: Comunicação Funcional, Comunicação Social e Comunicação Académica, cada uma com oito itens. Constitui uma check-list de rápido preenchimento e de classificação dos comportamentos de cada aluno. A amostra integrou 120 alunos que frequentam o 1º ano do Ensino Básico na Região Norte, sendo 60 do género feminino e 60 do género masculino. Os resultados deste estudo evidenciam que existem diferenças estatisticamente significativas em relação à variável: i) estabelecimento de ensino na Comunicação Social, havendo um influencia no desempenho dos alunos nesta dimensão; ii) ação social na Comunicação Académica, havendo uma influencia no desempenho dos alunos nesta dimensão; e no iii) aproveitamento escolar, ao nível das disciplinas de Português e Matemática, influenciando assim o desempenho dos alunos nas três dimensões da escala ECIE.A confiabilidade da escala foi analisada pelo Alpha de Cronbach, que apresentou um valor de .972 considerado muito bom (Field, 2013), pelo que se pode considerar um instrumento válido para despiste de dificuldades comunicativas de alunos em idade escolar. Este estudo comprova a importância da implementação de um rastreio a nível nacional em alunos em idade escolar, contribuindo como um instrumento de despiste, identificação e monitorização de alunos em contexto educativo que frequentam o 1º ciclo do ensino básico.

Transfer RNAs (tRNAs) are central to protein synthesis, ensuring precise decoding of the genetic code by delivering aminoacids to the ribosome. Among all RNA species, tRNAs are the most heavily and diversely modified, with modifications playing critical roles in stability, folding, and function. Here, we present a comprehensive, isodecoder-level map of tRNA modifications in the human pathogen Vibrio cholerae. This map was generated by chemical-based sequencing methods, comparing wild-type and deletion strains. By assigning specific tRNA modifications to their cognate enzymes, we defined a comprehensive modification landscape in Vibrio cholerae and confirmed species-specific features, such as the presence of a functional TrmK enzyme, largely restricted to Gram-positive bacteria. Additionally, we detected a modification at U55 that occurs independently of TruB. To assess the biological significance of these modifications, we evaluated fitness under both standard conditions and subinhibitory antibiotic stress, and examined how modifications in the anticodon stem-loop region influence codon decoding efficiency and accuracy. Based on a comparative analysis of E. coli and V. cholerae, we discuss how species-specific differences in tRNA isodecoder gene repertoires may influence the functional impact and biological importance of tRNA modifications. This work provides the first experimentally validated, genome-wide map of tRNA modifications in V. cholerae, serving as a reference for future research into RNA modifications, translation regulation, and pathogen biology. This study charts the first genome-wide map of transfer RNA (tRNA) modifications in the cholera pathogen, Vibrio cholerae, revealing how chemical marks on tRNAs shape translation and stress responses. Using complementary chemical sequencing methods and a panel of targeted gene deletions, we assigned specific modifications to their enzymes across individual tRNA isodecoders. This integrative approach validates conserved features (e.g., Ψ55 and T54), and specific ones, such as an active TrmK that installs m¹A22 despite being considered largely restricted to Gram-positive bacteria, and uncovers enzyme interplay among dihydrouridine synthases. By testing mutant strains in standard and sub-inhibitory antibiotic conditions, we show that several modifications are dispensable for basal growth but become critical under proteotoxic stress, influencing fitness and translation accuracy, including stop-codon readthrough. Codon-specific reporter assays further demonstrate that modifications at wobble position 34 and at position 37 modulate decoding of distinct codon families, linking epitranscriptomic changes to gene expression programs. Comparative analysis with Escherichia coli suggests that species-specific tRNA isodecoder repertoires tune the functional impact of modifications. Our map provides an additional reference for studying RNA modification biology in pathogens and how it contributes to stress adaptation and virulence.

A 45-year-old woman presented with several months of right-sided headache, associated with vocal hoarseness, fever, night sweats and weight loss. Severe right-sided periorbital pain came in episodes lasting several hours, associated with ipsilateral partial ptosis, facial swelling and hyperaesthesia. Indomethacin and greater occipital nerve block were ineffectual; however, a transient symptomatic improvement had coincided with previous steroid treatment.She had a background of cocaine use. Longstanding sinus complaints were investigated with nasen- doscopy, revealing nasal septal crusting and a hole in the soft palate. Fluctuating lymphadenopathy on previous imaging was investigated with blood tests, showing persistently raised ESR and ANCA positivity. Normal eosinophil counts.Serial MRI head scans showed evidence of worsening inflammatory, sclerotic and bony erosive changes to the midfacial skull base. The nasal septum and turbinates were obliterated, and maxillary/ethmoid/sphenoid sinuses were persistently effused. Granulomatosis with polyangiitis was diagnosed, and treatment with high-dose steroids and mycophenolate mofetil was commenced. Headache symptoms convinc- ingly improved.We present a case of headache with atraumatic midline skull base destruction, in a patient satisfying diagnostic criteria for granulomatosis with polyangiitis [1-2]. However, chronic cocaine use can have over- lapping clinical, immunological and radiological features [3-6]. Recent literature is reviewed to evaluate this diagnostic challenge [8-10].

We have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternative splice site use, intron retention), differential 5′ UTR (initiation of transcription) use, and differential 3′ UTR (alternative polyadenylation) use. These results demonstrate that the regulatory effects of genetic variation in a normal human population are far more complex than previously observed. This extra layer of molecular diversity may account for natural phenotypic variation and disease susceptibility.

SUMMARY Background To explore at what age youth start using tobacco and/or nicotine products, which product is used first, product initiation sequences, and whether some socio-demographic characteristics are associated with substance use initiation. Methods Data were collected from an online questionnaire disseminated through social media and professional partners, targeting youth aged 14–25 in French-speaking Switzerland in August 2022. The final sample included 1362 participants. Respondents were asked whether they had already used cigarettes, e-cigarettes, hookah, snus, or cannabis at least once in their life (yes/no) and the age of the first time was asked for each substance when the answer was positive. Additionally, participants were asked about their substance use in the past 30 days. Respondents were classified according to age at onset of each tobacco/nicotine and cannabis product, and comparisons were made based on sociodemographic variables, including gender (cisgender female/cisgender male/transgender), perceived socioeconomic status (below average/average/above average), and age. Results Overall, in addition to those who reported no consumption, four distinct initiation profiles emerged from the classification. Cigarettes remain the most commonly used first product with an average age of 15.7 years. While cigarettes and hookah are present in all profiles, the order of first consumption varies from one profile to another, with cigarettes coming first in two profiles, hookah in one and e-cigarettes in the last. Furthermore, while the most common profile contains experimental consumption of the five products considered, some profiles do not contain cannabis, e-cigarettes and/or snus, for example. When divided by age groups, both 14-17-year-olds and 18-21-year-olds reported cigarette as their first product of initiation. Across the separate age groups (14–17, 18–21, 22–25), cigarettes consistently emerge as the primary used on average. Conclusions Cigarettes remain the first product to be used, but the younger the respondents, the earlier they start using e-cigarettes, and very close to cigarettes. Regarding current consumption patterns, e-cigarettes are becoming increasingly prominent.

Naturally and anthropogenically emitted aerosols, which are determined by their physical and chemical properties, have an impact on both air quality and the radiative properties of the earth. An important source of atmospheric particulate matter (PM) in South Africa is household combustion for space heating and cooking, which predominantly occurs in low-income urban settlements. The aim of this study was to conduct a detailed size-resolved assessment of chemical characteristics of aerosols associated with household combustion through the collection of particulates in low-income urban settlements in South Africa to quantify the extent of the impacts of atmospheric pollution. Outdoor (ambient) and indoor aerosols in different size fractions were collected during summer and winter in four low-income urban settlements located in the north-eastern interior on the South African Highveld, i.e. Kwadela, Kwazamokuhle, Zamdela, and Jouberton. Mass concentration and chemical composition was determined for three size fractions, namely, PM1, PM2.5, and PM2.5−10. The highest concentrations of particulates were measured indoors with the highest mass concentration determined in the indoor PM2.5−10 (coarse) size fraction. However, the highest mass concentrations were determined in PM1 in all outdoor aerosol samples collected during winter and summer, and in indoor samples collected during summer. Significantly higher concentrations were determined for SO4-2 in outdoor and indoor particulates compared to other ionic species, with NH4+ and NO3- being the second most abundant. SO4-2 and NH4+ almost exclusively occurred in the PM1 size fraction, while NO3- was the major constituent in the larger size fractions. The highest SO4-2 levels were recorded for the winter and summer outdoor campaigns conducted at Zamdela, while NO3- and NH4+ concentrations were higher during the winter outdoor campaign. The combined concentrations of trace elements were higher for indoor particulates compared to outdoor aerosols, while the total trace element concentrations in PM1 were substantially higher than levels thereof in the two larger size fractions of particulates collected during all sampling campaigns. No distinct seasonal trend was observed for the concentrations of trace elements. Na, Ca, and Cr had the highest concentrations in particulates collected during outdoor and indoor sampling campaigns. Ni concentrations in outdoor and indoor aerosols exceeded the annual average European standard. PM1 collected during all sampling campaigns in low-income urban settlements had the highest organic carbon (OC) and elemental carbon (EC) concentrations. The highest OC and EC levels were determined in PM1 collected during the winter indoor campaign. OC and EC concentrations were highest during winter, which can be attributed to changes in meteorological patterns and increased household combustion during winter. Low OC/EC ratios determined for particulates collected in low-income urban settlements are indicative of OC and EC being mainly associated with local sources of these species. OC concentrations determined in this study were an order of magnitude lower than OC concentrations determined for ambient aerosols collected in the north-eastern interior of South Africa, while similar EC levels were measured. According to estimated dust concentrations, it was indicated that dust is the major constituent in all size ranges of particulates collected in this study, while trace elements were the second most abundant. However, trace elements made the highest contribution to indoor PM1 and PM1−2.5 mass. Mass concentrations and chemical concentrations determined for aerosols collected in low-income settlements reflect the regional impacts of anthropogenic sources in the north-eastern interior of South Africa and the influence of local sources.

The aim of this practice report is to discuss the implementation of a service-learning module developed to support the psychological wellbeing of postgraduate students and older adults in the community, with a view to fostering their connection and tackling loneliness in both populations. The module, 'Self-Identity, Intergenerational and Intercultural Learning' (SIIL), was offered to students enrolled in the Mental Health Studies Master of Science at the Institute of Psychiatry, Psychology and Neuroscience, King's College London. The module included lectures on the scientific underpinnings of wellbeing and ageism positionally within intercultural and intergenerational contexts. Students were introduced to qualitative research with a focus on autoethnography. They engaged with older adults through phone conversations and undertook wellbeing-promoting experiential exercises and self-reflection. The interactions provided students the opportunity to learn at an academic and personal level, while allowing older adults to share their experiences during the COVID-19 pandemic. These lessons learnt will inform future practice. Future directions for further developments of this methodology in other disciplines are also discussed in this practice report.

The aim of this practice report is to discuss the implementation of a service-learning module developed to support the psychological wellbeing of postgraduate students and older adults in the community, with a view to fostering their connection and tackling loneliness in both populations. The module, ‘Self-Identity, Intergenerational and Intercultural Learning’ (SIIL), was offered to students enrolled in the Mental Health Studies Master of Science at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London. The module included lectures on the scientific underpinnings of wellbeing and ageism positionally within intercultural and intergenerational contexts. Students were introduced to qualitative research with a focus on autoethnography. They engaged with older adults through phone conversations and undertook wellbeing-promoting experiential exercises and self-reflection. The interactions provided students the opportunity to learn at an academic and personal level, while allowing older adults to share their experiences during the COVID-19 pandemic. These lessons learnt will inform future practice. Future directions for further developments of this methodology in other disciplines are also discussed in this practice report.

Comparative linkage mapping can rapidly facilitate the transfer of genetic information from model species to orphan species. This macrosynteny analysis approach has been extensively used in plant species, but few example are available in fungi, and even fewer in mushroom crop species. Among the latter, the Agaricus genus comprises the most cultivable or potentially cultivable species. Agaricus bisporus, the button mushroom, is the model for edible and cultivable mushrooms. We have developed the first genetic linkage map for the basidiomycete A. subrufescens, an emerging mushroom crop known for its therapeutic properties and potential medicinal applications. The map includes 202 markers distributed over 16 linkage groups (LG), and covers a total length of 1701 cM, with an average marker spacing of 8.2 cM. Using 96 homologous loci, we also demonstrated the high level of macrosynteny with the genome of A. bisporus. The 13 main LG of A. subrufescens were syntenic to the 13 A. bisporus chromosomes. A disrupted synteny was observed for the three remaining A. subrufescens LG. Electronic mapping of a collection of A. subrufescens expressed sequence tags on A. bisporus genome showed that the homologous loci were evenly spread, with the exception of a few local hot or cold spots of homology. Our results were discussed in the light of Agaricus species evolution process. The map provides a framework for future genetic or genomic studies of the medicinal mushroom A. subrufescens.