Translational Aspects Research Articles

A narrative review on allergy and exposure to domestic and non-domestic animals: favorable and unfavorable effects.

The aim of this contribution was to highlight the "favorable" and "unfavorable" roles of domestic and non-domestic animals on airway sensitization processes and on the type/severity of the clinical symptoms induced by their exposure. We performed a literature research in MEDLINE for allergic manifestations and animals. Pets can be "allergy friends" through mechanisms related to hygiene hypothesis and translational aspects, the dual role of IgG4 antibodies for pets, and their promising role as healthcare service animals (dogs). On the contrary, animals can be "allergy enemies" when inducing allergic sensitization and respiratory symptoms (sometimes leading to severe reactions), and also due to cross reactivity with other pets allergens, indirect exposure and ubiquity of their allergens, cross reactivity between Can f 5 and human prostate-specific antigen (PSA). Moreover, in some cases they can trigger anaphylaxis, induce occupational asthma, and act as pests. Finally, we must outline the modest efficacy of allergen immunotherapy (AIT) for their allergens. From a strictly allergological perspective, it is evident that the "negative" aspects resulting from exposure to domestic / non-domestic animals outweigh the "positive" aspects. As a consequence, it is up to humans to seek new ways to balance the pros and cons by exploring research areas that can allow the best possible coexistence with subjects at risk of allergy with domestic and non-domestic animals.

Current status and future directions in Food Protein-Induced Enterocolitis Syndrome (FPIES): An NIAID Workshop Report

Food Protein-Induced Enterocolitis (FPIES) is a non-IgE mediated GI food allergy characterized by delayed, protracted vomiting, accompanied by lethargy and pallor, usually 1-4 hours following ingestion of the food allergen. The pathophysiology of FPIES remains unknown and currently there are no diagnostic biomarkers available to assess disease activity or its resolution. Over the last two decades, FPIES has become increasingly recognized in both pediatric and adult patients. Forty years later after the initial FPIES description, the first international classification of diseases (ICD-10) code for FPIES was established and the first international consensus guidelines for diagnosis and management of FPIES was published. On June 22, 2022, the National Institute of Allergy and Infectious Diseases (NIAID) held its first virtual multidisciplinary workshop on FPIES. Various clinical and translational aspects of FPIES, as well as the important areas of unmet needs were discussed as priorities for future research during this 2-day virtual workshop. The following report provides a summary of content of the workshop, including updated literature on the topic areas, as well as providing a critical commentary on the state of FPIES.

Inhibiting ADAM17 enhances the efficacy of olaparib in ovarian cancer spheroids

Acquired or de novo resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) is a major challenge to ovarian cancer treatment. Therefore, strategies to overcome PARPi resistance are critical to improve prognosis. The purpose of this study is to evaluate whether inhibition of ADAM17 sensitizes ovarian cancer to treatment with olaparib, a PARPi, thereby bypassing resistance mechanisms and improving treatment response. Thus, we analyzed the effect of olaparib in combination with the ADAM17 inhibitor GW280264X in ovarian cancer using a 2D monolayer and a 3D spheroid model followed by a multicontent readout (viability, caspase activation and cytotoxicity). To emphasize the translational aspect of our work, we performed corresponding experiments on primary cells derived from ovarian cancer patients initially screened for their mutation status of the breast cancer gene (BRCA 1/2). In 2D, we observed a significant reduction in cell viability and a subsequent increase in apoptosis of the combined treatment (olaparib + GW280264X) compared with olaparib mono-treatment. The combined treatment allows a substantial dose reduction of olaparib rendering a strong synergistic effect. Using a 3D spheroid model from primary cells, we confirmed the 2D monoculture results and demonstrated not only increased caspase activity under the combined treatment but also a substantial gain in cytotoxicity compared to the mono-treatment. Our study proposes ADAM17 inhibition sensitizing ovarian cancer to olaparib treatment and improving treatment response.

Central role of hypoxia-inducible factor-1α in metabolic reprogramming of cancer cells: A review.

Metabolic reprogramming is one of the characteristics of tumor cell metabolism. In tumor cells, there are multiple metabolic enzymes and membrane proteins to regulate metabolic reprogramming, and hypoxia inducible factor-1α (HIF-1α) can be regulated in transcription, translation, posttranslational modification and other aspects through multiple pathways, and HIF-1α affects multiple metabolic enzymes and membrane proteins during metabolic reprogramming, thus playing a central role in the metabolic reprogramming process, and thus has some implications for tumor therapy and understanding chemotherapy drug resistance. HIF-1α affects a number of metabolic enzymes and membrane proteins in the metabolic reprogramming process, thus playing a central role in the metabolic reprogramming process, which has certain significance for the treatment of tumors and the understanding of chemotherapeutic drug resistance. In this paper, we review the central role of HIF-1α in metabolic reprogramming, chemotherapeutic agents targeting HIF-1α, and chemotherapeutic drug resistance.

Choline geranate (CAGE): A multifaceted ionic liquid for drug delivery

Ionic liquids, organic salts in a liquid state below 100 °C, have traditionally been associated with industrial applications. Recent research has introduced a new generation of ionic liquids, designed from biocompatible ions, to enable applications in drug delivery. Here, I provide a historical perspective, development status and applications of a leading example of biocompatible ionic liquids, a salt of Choline And Geranic acid (CAGE). Since its first report in 2014, CAGE has opened multiple drug delivery applications including transdermal, oral, buccal, sustained release, tissue ablation, periodontitis and hand hygiene, among others. CAGE-based products have been tested in more than 200 patients through multiple Phase 1 and Phase 2 clinical studies, including successful use in a Phase 2 clinical study in Atopic Dermatitis patients. CAGE became the first ‘drug delivery ionic liquid’ to enter into clinical trials. This article summarizes the key fundamental and translational aspects of CAGE as pertained to its use in drug delivery.

Cognitive Aspects of Translation: The Latest Research in Psycholinguistics and Cognitive Science

The study of the cognitive aspect of translation opens up new possibilities for understanding and analysing the translation process through the prism of cognitive science. By analysing the cognitive processes that take place in the translator's brain while performing translation, it is possible to reveal various aspects of this complex and multifaceted process. The purpose of this article is to conduct a literature review of cognition-oriented translation studies in order to contribute to the development of the science of translation studies. The method included the analysis of related literature from the scientific databases Scopus and Google Scholar. As a result of this study, advanced theoretical models were put forward and developed to reveal the so-called “black box” of the translator, which is considered a key aspect in understanding the cognitive processes of translation. These theoretical approaches aimed to uncover the internal mechanism and strategies used by the translator when performing translation in order to reveal and analyse how these processes occur in the translator's brain. Conclusions – the research focused on translation processes has great potential, as it uses the latest theoretical models and research methods from related cognitive disciplines such as cognitive psychology, cognitive linguistics, neurophysiology and computational linguistics. The paper attempts to identify challenges in cognitive translation research in order to contribute to a broader understanding of the cognitive aspects of translation and to help address key challenges in this area.

Linguistic, Aesthetic And Cultural Aspects Of Translating Literary Texts (Arabic-English): A Model For Translation Pedagogy

The main aim of this paper is to explore the different linguistic, aesthetic, and cultural aspects of literary translation. The paper examines the various features of literary translation at both macro and micro levels. It focuses on those features of literary texts that are characteristic of literary works. First, we follow the standard linguistic paradigm in the discussion of literary translation, including phonology, morphology, syntax, semantics, and the aesthetic and cultural features of literary texts. The qualitative method is used to explore the various features of literary translation to identify the recurring linguistic and literary devices lacking systematic forms and patterns to find a comparable genre-specific form in the target language. The model proposed consists of five stages: (1) Retention of sound devices, (2) Retention of syntactic patterns, (3) Retention of semantic features, (4) Retention of figurative language, and (5) Retention of the cultural aspects. The model is a descriptive model for analyzing literary translation procedures and can be used as a pedagogical model for translation practice. Findings show that employing this model would offer translation students new insights to describe challenging linguistic, aesthetic, and cultural features in the source texts to think of some practical solutions for translating literary works.

Single-molecule tracking reveals dynamic regulation of ribosomal scanning.

How eukaryotic ribosomes traverse messenger RNA (mRNA) leader sequences to search for protein-synthesis start sites remains one of the most mysterious aspects of translation and its regulation. While the search process is conventionally described by a linear "scanning" model, its exquisitely dynamic nature has restricted detailed mechanistic study. Here, we observed single Saccharomyces cerevisiae ribosomal scanning complexes in real time, finding that they scan diverse mRNA leaders at a rate of 10 to 20 nt s-1. We show that specific binding of a protein to its mRNA leader sequence substantially arrests scanning. Conversely, impairing scanning-complex guanosine 5'-triphosphate hydrolysis results in native start-site bypass. Our results illustrate an mRNA-centric, kinetically controlled regulatory model where the ribosomal pre-initiation complex amplifies a nuanced energetic landscape to regulate scanning and start-site selection fidelity.

X- vs. Y-chromosome influences on human behavior: a deep phenotypic comparison of psychopathology in XXY and XYY syndromes

BackgroundDo different genetic disorders impart different psychiatric risk profiles? This question has major implications for biological and translational aspects of psychiatry, but has been difficult to tackle given limited access to shared batteries of fine-grained clinical data across genetic disorders.MethodsUsing a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs)—Klinefelter (XXY/KS) and XYY syndrome (n = 102 and 64 vs. n = 74 and 60 matched XY controls, total n = 300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X- vs. Y-chromosome effects, and potential relevance for normative sex differences.ResultsWe show that XXY/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY/KS which is strongly correlated with that of XYY (r = .75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS/XXY for most traits except mood/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY/KS on social problems. XXY/KS and XYY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ.ConclusionsThis work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X- and Y-chromosome on human behavior.

Control of nerve-mediated and urothelial ATP release by a protein kinase G-dependent pathway in the mouse bladder

Aim:ATP signalling is involved in urinary bladder motor and sensory pathways, including stimulation-mediated release from parasympathetic varicosities to detrusor muscle and from urothelial cells when mechanically stressed. Both modalities are present in humans and other mammals but are especially prominent in overactive bladder syndromes. There is therefore an unmet need to understand how to regulate such release. This study tested the hypothesis that the nitric oxide (NO•)/ soluble guanylate cyclase (sGC)/ cyclic GMP/ protein kinase-G (PKG) pathway has a central role. Methods:In vitro nerve-mediated contractions and ATP/acetylcholine (ACh) release were measured from bladder wall strips, as was ATP release from urothelial cell suspensions subject to mechanical stresses. Enhanced spontaneous contractile activity was also measured in bladder wall preparations of spinal cord-injured mice. Interventions were designed to increase cellular cGMP levels (a cell-permeable cGMP analogue, a NO•donor, a phosphodiesterase inhibitor (PDEI), a sGC activator), or agents to reduce activity of pathway enzymes (sCG or PKG). Results:ATP-dependent contractions were reduced by the above interventions, as was ATP release; but ACh-dependent contractions and ACh release were unaffected. Spontaneous contractile activity was also reduced by the cGMP analogue and by a PDEI. ATP release from urothelial cell suspensions was also reduced by similar interventions. Conclusions:ATP release from efferent nerves and from urothelial cells were selectively reduced by upregulating the NO•/sGC/cGMP/PKG pathway. Translational aspects are discussed with respect to purinergic pathways and overactive bladder pathologies.

Interactions between sleep, inflammation, immunity and infections: A narrative review.

Over the past decades, it has become increasingly evident that sleep disturbance contributes to inflammation-mediated disease, including depression, mainly through activation of the innate immune system and to an increased risk of infections. A comprehensive literature search was performed in PubMed to identify relevant research findings in the field of immunity, inflammation and infections, with a focus on translational research findings from the past 5 years. Physiological sleep is characterized by a dynamic interplay between the immune system and sleep architecture, marked by increased innate immunity and T helper 1 (Th1) -mediated inflammation in the early phase, transitioning to a T helper 2 (Th2) response dominating in late sleep. Chronic sleep disturbances are associated with enhanced inflammation and an elevated risk of infections, while other inflammatory diseases may also be affected. Conversely, inflammation in response to infection can also disrupt sleep patterns and architecture. This narrative review summarizes current data on the complex relationships between sleep, immunity, inflammation and infections, while highlighting translational aspects. The bidirectional nature of these interactions are addressed within specific conditions such as sleep apnea, HIV, and other infections. Furthermore, technical developments with the potential to accelerate our understanding of these interactions are identified, including advances in wearable devices, artificial intelligence, and omics technology. By integrating these tools, novel biomarkers and therapeutic targets for sleep-related immune dysregulation may be identified. The review underscores the importance of understanding and addressing immune imbalance related to sleep disturbances to improve disease outcomes.

A Sociological Study into the Impact of Capital on Moss Roberts’ Translation—<i>Three Kingdoms: A Historical Novel</i>

The study of translation has undergone a shift from language-level analysis to a cultural turn and, subsequently, a return to a more macroscopic social perspective. As social research in translation primarily targets external factors, it falls under centrifugal research in translation studies. To sustain the vitality of translation studies, there is a need for a balanced approach, combining centrifugal research with centripetal research. Moss Roberts’ translation of <i>San Guo Yan Yi</i> is initiated by China Foreign Language Press and co-published by China and the US presses in 1991. It is considered the most academic complete English version of <i>San Guo Yan Yi</i>. Drawing on the social practice theory of French sociologist Pierre Bourdieu, this study analyzes Moss Roberts’ translation practices of and the influence of capital in the English translation and dissemination field. It attempts a micro-level and reverse study of sociological aspects of translation by examining three key aspects: the influence of cultural capital, the impact of social capital, and the manipulation of power capital. The results showed that Moss Roberts’ translation practices are deeply influenced by his cultural, social and power capital. Among them, his cultural capital enables the translation to be academic; his social capital empowers it to be accurate and faithful; and his power capital manipulates it where religious information arises.

Reconsidering freeze-induced protein aggregation: Air bubbles as the root cause of ice-water interface stress

Freeze-induced stress causing aggregation of proteins has typically been primarily attributed to the ice-water interface. However, we hypothesize that the underlying observed and perceived detrimental effect of ice is, to some extent, attributed to air bubbles expelled from ice crystal lattices or to nanobubbles existing prior to freezing. The reduction of dissolved air was achieved via a deaeration process by placing samples in a reduced pressure chamber, while the reduction of nanobubbles was achieved by filtering samples via a syringe filter. The results showed that the reduction of both dissolved air molecules and stable colloidal nanobubbles in a bovine IgG solution prior to freezing led to a significant decrease in aggregation after thawing compared to untreated samples (∼6,000 vs. ∼ 40,000 particles/mL at a freezing rate of 100 K/s, respectively). The deaeration-filtration treatment works additively with cryoprotectants such as trehalose, further reducing the freeze-induced aggregation of IgG. The results also demonstrated that air–water interfacial aggregation of IgG in bulk liquid samples is a time-dependent process. The number of IgG subvisible particles increased with time and temperature, suggesting that random collisions of denatured molecules promoted the formation of aggregates with spherical morphology. In contrast, the IgG subvisible count after freeze-thawing had already reached its nominal value, suggesting a time-independent process where denatured protein molecules were compressed between ice crystals into filament-like aggregates. In summary, the findings shift the current paradigm from ice crystals being the main destabilizing factor during freezing to air bubbles, although the two are intertwined. From a translational aspect, this study underscores the value of deaeration-filtration as an essential supplemental process that can be applied in addition to formulation approaches such as the use of cryoprotectants to further reduce freezing stress on proteins and increase their stability.

On the construction of translation cultures*

Abstract The paper by Erich Prunč introduces and develops the concept of translationskultur, a concept that captures cultural and social aspects of translation. Expanding beyond the narrow traditional views of equivalence and text oriented approaches that were dominant in translation studies when Prunč developed the concept, Prunč presents translation as a critical practice not only in mediating between languages but also as an essential act of transcultural communication. The concept of translationskultur is theorized as a self-referential, self-regulating subsystem of culture, characterized by a set of socially established norms and behaviors shared by individuals involved in translation. Prunč emphasizes the complexity of translation cultures, which arise from the delicate compromises among all stakeholders engaged in or affected by the translation process, including translators, authors, and recipients. Translation cultures are shaped by power dynamics within the field, and factors like societal status and resource allocation contribute to the establishment of hierarchies relevant for translation practices. By introducing this concept, Prunč moreover aims to encourage a conscientious reflection on the roles and responsibilities of translators and interpreters, their loyalties towards themselves, and advocates for more confident and self-critical agents acting towards ideals of a prototypical democratic translation culture. The paper concludes with the vision of translators and interpreters who are aware of their significant role in shaping discourses and who exercise their power with a sense of professional pride and ethical diligence.

Aspects of translation of Russian linguistic realities of N.V. Gogol’s novel “Dead Souls” into Chinese language

Abstract In the modern world, characterised by the increasing popularity of world literature, there exists an escalating demand for accurate and culturally adapted translations that convey the semantic accuracy and meaning of the original text. The purpose of this study is to analyze the specific features of translating antonyms into Chinese reflecting everyday realities in N.V. Gogol’s novel “Dead Souls”. The following methods were used to achieve the research objectives: hypothetical-deductive, content analysis, and comparative. The study determined that the novel “Dead Souls” is rich in Russian everyday realities and antonyms that convey the linguocultural features of the time within the context of the literary work. In addition, it was revealed that translators face the challenge of conveying Russian everyday realities and cultural features in the Chinese translation. This includes the problem of adapting antonyms that may be unfamiliar or have a different meaning in Chinese culture. The translation of antonyms must maintain semantic accuracy and comparability with the original to convey the meaning and contrast that antonyms create in the text. The study showed that the translation of antonyms can influence Chinese readers’ perception of the text. Their correct rendering preserves the meaning and structure of the original, which is significant for a full understanding of the literary work. As a result of a comparative analysis of Chinese translations of N.V. Gogol’s novel “Dead Souls”, various aspects influencing the translation of antonyms and their role in conveying Russian everyday realities were revealed. Practical significance lies in the use of the findings of this study by the researchers engaged in the translation of literary works, as well as specialists in the fields of literary studies, linguistics, and translation studies.

CONNECTION BETWEEN ARTISTIC EDITING AND ARTISTIC TRANSLATION

This scientific article investigates the necessity of adhering to linguistic norms and existing editorial principles when editing literary translations from foreign languages, taking into account the shared aspects of translation and editorial criteria. The study focuses on the quality of editing the Uzbek translation of the novel The Alchemist, compared to its English and Russian versions. It examines issues such as preserving the semantic features of the text during the editing process and provides suggestions and recommendations for addressing shortcomings that arise in the editorial process.

Western Diet-Induced Nonalcoholic Fatty Liver Disease Mice Mimic the Key Transcriptomic Signatures Observed in Humans

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption or a secondary cause of hepatic steatosis. The prevalence of NAFLD is increasing worldwide and its management has become a public health concern. Animal models are traditionally used to elucidate disease mechanisms and identify potential drug targets; however, their translational aspects in human diseases have not been fully established. This study aimed to clarify the utility of animal models for translational research by assessing their relevance to human diseases using gene expression analysis. Weighted gene co-expression network analysis of liver tissues from Western diet (WD)-induced NAFLD mice was performed to identify the modules associated with disease progression. Moreover, the similarity of the gene co-expression network across species was evaluated using module preservation analysis. Nineteen disease-associated modules were identified. The brown module was positively associated with disease severity, and functional analyses indicated that it may be involved in inflammatory responses in immune cells. Moreover, the gene co-expression network of the brown module was highly preserved in human NAFLD liver gene expression datasets. These results indicate that WD-induced NAFLD mice have similar gene co-expression networks (especially genes associated with inflammatory responses) to humans and are thought to be a useful experimental tool for preclinical research on NAFLD.

Pragmatic Strategies in Artistic Translation: Balancing Creativity and Cultural Adaptation

This study investigates the communicative-pragmatic aspects of artistic translation, focusing on how translators navigate the complexities of preserving the original text's artistic and aesthetic integrity while adapting it to a different cultural and linguistic context. Despite extensive research in translation studies, a systematic exploration of pragmatic motivations and strategies in artistic translation remains underdeveloped. This research addresses this gap by employing a comprehensive methodological approach that includes descriptive-analytical, semantic-stylistic, and literary analysis of original texts and their translations. The findings highlight the critical role of the translator's creative interpretation in maintaining the balance between fidelity to the original text and the need for cultural adaptation. The results demonstrate that pragmatic strategies significantly influence the translation process, particularly in how verbal-artistic information is transformed to resonate with the target audience. The study also suggests that these strategies are essential for achieving functional equivalence and preserving the artistic value of the original work. The implications of this research are significant for both translation theory and practice, emphasizing the need for enhanced training programs that focus on the development of creative and pragmatic skills in translators. Further research is recommended to explore the emotional and experiential dimensions of translation, as these aspects remain crucial yet underexplored in current literature.

Neurodevelopmental disorder-associated CYFIP2 regulates membraneless organelles and eIF2α phosphorylation via protein interactors and actin cytoskeleton.

De novo variants in the Cytoplasmic FMR1-interacting protein 2 (CYFIP2) have been repeatedly associated with neurodevelopmental disorders and epilepsy, underscoring its critical role in brain development and function. While CYFIP2's role in regulating actin polymerization as part of the WAVE regulatory complex (WRC) is well-established, its additional molecular functions remain relatively unexplored. In this study, we performed unbiased quantitative proteomic analysis, revealing 278 differentially expressed proteins (DEPs) in the forebrain of Cyfip2 knock-out embryonic mice compared to wild-type mice. Unexpectedly, these DEPs, in conjunction with previously identified CYFIP2 brain interactors, included not only other WRC components but also numerous proteins associated with membraneless organelles (MLOs) involved in mRNA processing and translation within cells, including the nucleolus, stress granules, and processing bodies. Additionally, single-cell transcriptomic analysis of the Cyfip2 knock-out forebrain revealed gene expression changes linked to cellular stress responses and MLOs. We also observed morphological changes in MLOs in Cyfip2 knock-out brains and CYFIP2 knock-down cells under basal and stress conditions. Lastly, we demonstrated that CYFIP2 knock-down in cells, potentially through WRC-dependent actin regulation, suppressed the phosphorylation levels of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), thereby enhancing protein synthesis. These results suggest a physical and functional connection between CYFIP2 and various MLO proteins and also extend CYFIP2's role within the WRC from actin regulation to influencing eIF2α phosphorylation and protein synthesis. With these dual functions, CYFIP2 may fine-tune the balance between MLO formation/dynamics and protein synthesis, a crucial aspect of proper mRNA processing and translation.

Translational Aspects of 3D and 4D Printing and Bioprinting.

Three-dimensional (3D) printed medical devices include orthopedic and craniofacial implants, surgical tools, and external prosthetics that have been directly used in patients. While the advances of additive manufacturing techniques in the production of medical devices have been on the rise, clinical translation of living cellular constructs face significant limitations in terms of regulatory affairs, process technology, and materials development. In this perspective, the current status-quo of 3D and four-dimensional (4D) (bio)printing is summarized, current advancements are discussed and the challenges that need to be addressed for improved industrial translation and clinical applications of bioprinting are highlighted. It is focused on a multidisciplinary approach in discussing the key translational considerations, from the perspective of industry, regulatory bodies, funding strategies, and future directions.