Advances in basic biology and translation in islet research
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Stem cell transcriptional profiles from mouse subspecies reveal cis-regulatory evolution at translation genes
A key goal of evolutionary genomics is to harness molecular data to draw inferences about selective forces that have acted on genomes. The field progresses in large part through the development of advanced molecular-evolution analysis methods. Here we explored the intersection between classical sequence-based tests for selection and an empirical expression-based approach, using stem cells from Mus musculus subspecies as a model. Using a test of directional, cis-regulatory evolution across genes in pathways, we discovered a unique program of induction of translation genes in stem cells of the Southeast Asian mouse M. m. castaneus relative to its sister taxa. We then mined population-genomic sequences to pursue underlying regulatory mechanisms for this expression divergence, finding robust evidence for alleles unique to M. m. castaneus at the upstream regions of the translation genes. We interpret our data under a model of changes in lineage-specific pressures across Mus musculus in stem cells with high translational capacity. Our findings underscore the rigor of integrating expression and sequence-based methods to generate hypotheses about evolutionary events from long ago.
Cultural nuances in subtitling the religious discourse marker wallah in Jordanian drama into English
This study examines the strategies and challenges of subtitling the religious discourse marker والله wallah (by God) in Jordanian Arabic drama on Netflix. Two works, the series Jinn (2019) and the film Theeb (2014), are chosen as the corpus of the data. The study analyses the pragmatic functions of the religious marker wallah, which Arabs usually use to swear to God in different contexts and examines its English subtitles. The theoretical framework partially employs Vinay and Darbelnet’s (1995) literal translation and omission strategies and Baker’s (2018) translation approaches, including equivalence and paraphrase. A qualitative analysis is conducted to analyse the functions of occurrences of this marker in its pragmatic context, along with its subtitling into English. The study found that the religious marker is frequently omitted in the subtitles or rendered into various linguistic elements such as speech acts, intensifiers, emphatic expressions, filler words, and sarcastic utterances. wallah was either paraphrased or literally translated in some instances. The study concludes that it is necessary to employ unique techniques to overcome the cultural and linguistic gaps, depending on the function of the religious discourse marker, and to improve the reliability and quality of interpreting religious markers in audiovisual settings.
Multimodal insights: enhancing cultural promotion through analysis of Saudi Arabian audiovisual productions
This research explores the application of Dicerto’s (2018) multimodal pragmatic model in analyzing Arabic audiovisual productions for translation purposes, focusing on enhancing cultural promotion. Employing a qualitative descriptive analysis approach, the study examines samples from Saudi productions that promote tourism, mainly focusing on Saudi coffee and its cultural traditions to enlighten foreign visitors about Saudi culture. The analysis reveals that Dicerto’s model provides a clear framework for achieving semantic fidelity in translation, ensuring that the translated text closely resembles its original in interpretative richness. Central to this framework is the principle of optimal relevance, wherein the sender intends the message to be maximally pertinent to the audience, thereby justifying the recipient’s cognitive effort in processing it and facilitating access to the sender’s intentions. This research sheds light on the effectiveness of applying multimodal analysis models in cultural promotion efforts through audiovisual productions, particularly in Saudi Arabian tourism promotion.
A capless hairpin-protected mRNA vaccine encoding the full-length Influenza A hemagglutinin protects mice against a lethal Influenza A infection
The success of mRNA vaccines in controlling the COVID 19 pandemic has confirmed the efficacy of synthetically synthesized mRNA in humans and has also provided a blueprint on how to design them in terms of molecular structure and cost. We describe a mRNA vector that, unlike linear mRNAs used in current vaccines/therapeutics, does not require a 5′ cap to function. The described mRNA vector initiates translation from an internal ribosomal entry site (IRES) and contains specially designed self-folding secondary structures (hairpins) to protect the 5′ end against degradation, dramatically improving its stability. The produced mRNA did not require any additional modifications for functionality. The 5′ hairpins completely inhibited cap-dependent translation, and all vectors containing them required an IRES to express protein. When this capless mRNA vector was constructed to express the full-length Influenza A membrane protein hemagglutinin (HA), complexed with pre-formed lipid-based nanoparticles, and then injected into mice as a vaccine, it generated high titers of anti-HA antibodies and protected mice against a lethal dose of Influenza A.
Transgenerational inheritance of diabetes susceptibility in male offspring with maternal androgen exposure
Androgen exposure (AE) poses a profound health threat to women, yet its transgenerational impacts on male descendants remain unclear. Here, employing a large-scale mother-child cohort, we show that maternal hyperandrogenism predisposes sons to β-cell dysfunction. Male offspring mice with prenatal AE exhibited hyperglycemia and glucose intolerance across three generations, which were further exacerbated by aging and a high-fat diet. Mechanistically, compromised insulin secretion underlies this transgenerational susceptibility to diabetes. Integrated analyses of methylome and transcriptome revealed differential DNA methylation of β-cell functional genes in AE-F1 sperm, which was transmitted to AE-F2 islets and further retained in AE-F2 sperm, leading to reduced expression of genes related to insulin secretion, including Pdx1, Irs1, Ptprn2, and Cacna1c. The methylation signatures in AE-F1 sperm were corroborated in diabetic humans and the blood of sons with maternal hyperandrogenism. Moreover, caloric restriction and metformin treatments normalized hyperglycemia in AE-F1 males and blocked their inheritance to offspring by restoring the aberrant sperm DNA methylations. Our findings highlight the transgenerational inheritance of impaired glucose homeostasis in male offspring from maternal AE via DNA methylation changes, providing methylation biomarkers and therapeutic strategies to safeguard future generations’ metabolic health.
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