Splicing is functionally coupled to transcription, linking the rate of RNA polymerase II (Pol II) elongation and the ability of splicing factors to recognize splice sites (ss) of various strengths. ...In most cases, slow Pol II elongation allows weak splice sites to be recognized, leading to higher inclusion of alternative exons. Using CFTR alternative exon 9 (E9) as a model, we show here that slowing down elongation can also cause exon skipping by promoting the recruitment of the negative factor ETR-3 onto the UG-repeat at E9 3′ splice site, which displaces the constitutive splicing factor U2AF65 from the overlapping polypyrimidine tract. Weakening of E9 5′ ss increases ETR-3 binding at the 3′ ss and subsequent E9 skipping, whereas strengthening of the 5′ ss usage has the opposite effect. This indicates that a delay in the cotranscriptional emergence of the 5′ ss promotes ETR-3 recruitment and subsequent inhibition of E9 inclusion.
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•Alternative splicing is coupled to transcriptional elongation•Slow elongation either up- or downregulates exon inclusion depending on the exon•In CFTR exon 9, slow elongation favors recruiting the negative splicing factor ETR3•Delaying transcription of exon 9 5′ ss favors ETR-3 binding and exon 9 skipping
Splicing takes place cotranscriptionally and is coupled to transcription. Many alternative splicing decisions depend on the rate RNA Pol II elongation. Although the prevailing paradigm indicates that slow elongation promotes exon inclusion, Dujardin et al. describe a mechanism explaining why, in some exons, slow elongation has the opposite effect.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
RNA-binding proteins (RBPs) are essential for the development and function of the immune system. They interact dynamically with RNA to control its biogenesis and turnover by transcription-dependent ...and transcription-independent mechanisms. In this Review, we discuss the molecular mechanisms by which RBPs allow gene expression changes to occur at different speeds and to varying degrees, and which RBPs regulate the diversity of the transcriptome and proteome. These proteins are nodes for integration of transcriptional and signaling networks and are intimately linked to intermediary metabolism. They are essential components of regulatory feedback mechanisms that maintain immune tolerance and limit inflammation. The role of RBPs in malignancy and autoimmunity has led to their emergence as targets for the development of new therapeutic modalities.
Alternative splicing was discovered simultaneously with splicing over three decades ago. Since then, an enormous body of evidence has demonstrated the prevalence of alternative splicing in ...multicellular eukaryotes, its key roles in determining tissue- and species-specific differentiation patterns, the multiple post- and co-transcriptional regulatory mechanisms that control it, and its causal role in hereditary disease and cancer. The emerging evidence places alternative splicing in a central position in the flow of eukaryotic genetic information, between transcription and translation, in that it can respond not only to various signalling pathways that target the splicing machinery but also to transcription factors and chromatin structure.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
•The 18.7% of the sample revealed depressive symptomatology, the 21.6% anxiety and the 15.8% PSTD.•Being older, economic stability and information were negatively related to the ...symptomatology.•Female, previous diagnoses or Covid-19 symptoms were associated with symptomatology.•Spiritual well-being was a common protector for all symptomatology and the loneliness a predictor.
The pandemic caused by Covid-19 has been an unprecedented social and health emergency worldwide. This is the first study in the scientific literature reporting the psychological impact of the Covid-19 outbreak in a sample of the Spanish population. A cross-sectional study was conducted through an online survey of 3480 people. The presence of depression, anxiety and post-traumatic stress disorder (PTSD) was evaluated with screening tests from 14 March. Sociodemographic and Covid-19-related data was collected. Additionally, spiritual well-being, loneliness, social support, discrimination and sense of belonging were assessed. Descriptive analyses were carried out and linear regression models compiled. The 18.7% of the sample revealed depressive, 21.6% anxiety and 15.8% PTSD symptoms. Being in the older age group, having economic stability and the belief that adequate information had been provided about the pandemic were negatively related to depression, anxiety and PTSD. However, female gender, previous diagnoses of mental health problems or neurological disorders, having symptoms associated with the virus, or those with a close relative infected were associated with greater symptomatology in all three variables. Predictive models revealed that the greatest protector for symptomatology was spiritual well-being, while loneliness was the strongest predictor of depression, anxiety and PTSD. The impact on our mental health caused by the pandemic and the measures adopted during the first weeks to deal with it are evident. In addition, it is possible to identify the need of greater psychological support in general and in certain particularly vulnerable groups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Osteoporosis is a common chronic disease characterized by a decrease in bone mineral density, impaired bone strength, and an increased risk of fragility fractures. Fragility fractures are associated ...with significant morbidity, mortality and disability and are a major public health problem worldwide. The influence of nutritional factors on the development and progression of this disease can be significant and is not yet well established. Calcium intake and vitamin D status are considered to be essential for bone metabolism homeostasis. However, some recent studies have questioned the usefulness of calcium and vitamin D supplements in decreasing the risk of fractures. The adequate intake of protein, vegetables and other nutrients is also of interest, and recommendations have been established by expert consensus and clinical practice guidelines. It is important to understand the influence of nutrients not only in isolation but also in the context of a dietary pattern, which is a complex mixture of nutrients. In this review, we evaluate the available scientific evidence for the effects of the main dietary patterns on bone health. Although some dietary patterns seem to have beneficial effects, more studies are needed to fully elucidate the true influence of diet on bone fragility.
Abstract
BACKGROUND
Successful embryo implantation is a complex process that requires the coordination of a series of events, involving both the embryo and the maternal endometrium. Key to this ...process is the intricate cascade of molecular mechanisms regulated by endocrine, paracrine and autocrine modulators of embryonic and maternal origin. Despite significant progress in ART, implantation failure still affects numerous infertile couples worldwide and fewer than 10% of embryos successfully implant. Improved selection of both the viable embryos and the optimal endometrial phenotype for transfer remains crucial to enhancing implantation chances. However, both classical morphological embryo selection and new strategies incorporated into clinical practice, such as embryonic genetic analysis, morphokinetics or ultrasound endometrial dating, remain insufficient to predict successful implantation. Additionally, no techniques are widely applied to analyse molecular signals involved in the embryo–uterine interaction. More reliable biological markers to predict embryo and uterine reproductive competence are needed to improve pregnancy outcomes. Recent years have seen a trend towards ‘omics’ methods, which enable the assessment of complete endometrial and embryonic molecular profiles during implantation. Omics have advanced our knowledge of the implantation process, identifying potential but rarely implemented biomarkers of successful implantation.
OBJECTIVE AND RATIONALE
Differences between the findings of published omics studies, and perhaps because embryonic and endometrial molecular signatures were often not investigated jointly, have prevented firm conclusions being reached. A timely review summarizing omics studies on the molecular determinants of human implantation in both the embryo and the endometrium will help facilitate integrative and reliable omics approaches to enhance ART outcomes.
SEARCH METHODS
In order to provide a comprehensive review of the literature published up to September 2019, Medline databases were searched using keywords pertaining to omics, including ‘transcriptome’, ‘proteome’, ‘secretome’, ‘metabolome’ and ‘expression profiles’, combined with terms related to implantation, such as ‘endometrial receptivity’, ‘embryo viability’ and ‘embryo implantation’. No language restrictions were imposed. References from articles were also used for additional literature.
OUTCOMES
Here we provide a complete summary of the major achievements in human implantation research supplied by omics approaches, highlighting their potential to improve reproductive outcomes while fully elucidating the implantation mechanism. The review highlights the existence of discrepancies among the postulated biomarkers from studies on embryo viability or endometrial receptivity, even using the same omic analysis.
WIDER IMPLICATIONS
Despite the huge amount of biomarker information provided by omics, we still do not have enough evidence to link data from all omics with an implantation outcome. However, in the foreseeable future, application of minimally or non-invasive omics tools, together with a more integrative interpretation of uniformly collected data, will help to overcome the difficulties for clinical implementation of omics tools. Omics assays of the embryo and endometrium are being proposed or already being used as diagnostic tools for personalised single-embryo transfer in the most favourable endometrial environment, avoiding the risk of multiple pregnancies and ensuring better pregnancy rates.
Wearable cognitive assistants (WCA) are anticipated to become a widely-used application class, in conjunction with emerging network infrastructures like 5G that incorporate edge computing ...capabilities. While prototypical studies of such applications exist today, the relationship between infrastructure service provisioning and its implication for WCA usability is largely unexplored despite the relevance that these applications have for future networks. This paper presents an experimental study assessing how WCA users react to varying end-to-end delays induced by the application pipeline or infrastructure. Participants interacted directly with an instrumented task-guidance WCA as delays were introduced into the system in a controllable fashion. System and task state were tracked in real time, and biometric data from wearable sensors on the participants were recorded. Our results show that periods of extended system delay cause users to correspondingly (and substantially) slow down in their guided task execution, an effect that persists for a time after the system returns to a more responsive state. Furthermore, the slow-down in task execution is correlated with a personality trait, neuroticism, associated with intolerance for time delays. We show that our results implicate impaired cognitive planning, as contrasted with resource depletion or emotional arousal, as the reason for slowed user task executions under system delay. The findings have several implications for the design and operation of WCA applications as well as computational and communication infrastructure, and additionally for the development of performance analysis tools for WCA.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while ...preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome.
Not all platelet-rich plasma are created equal Cantero, Manuel Muñoz
Current opinion in obstetrics & gynecology,
2024-Jun-01, 2024-06-00, 20240601, Volume:
36, Issue:
3
Journal Article
Peer reviewed
This review aims to elucidate potential variations in clinical outcomes resulting from the use of different types of platelet-rich plasma (PRPs) in reproductive medicine. It seeks to explore the ...reasons behind the diverse results reported in various studies and assess the general features distinguishing different PRP formulations.
PRPs have found applications across diverse medical fields, generating controversy due to the variability in outcomes. The field of reproductive medicine, despite its limited published studies, is encountering a similar challenge as it integrates these treatments.
The multitude of PRP product brands in the market, coupled with 'home-made' PRPs, poses a significant barrier to establishing a common protocol for the preparation of standardized PRP products. This impediment hinders widespread adoption by clinicians, particularly in endometrial or ovarian treatments. Drawing from evidence in other medical disciplines, this review endeavors to compile essential characteristics that PRPs must possess, aiming to mitigate the impact of variables affecting results in forthcoming studies.
Lymphocytes require of constant and dynamic changes in their transcriptome for timely activation and production of effector molecules to combat external pathogens. Synthesis and translation of ...messenger (m)RNAs into these effector proteins is controlled both quantitatively and qualitatively by RNA binding proteins (RBPs). RBP‐dependent regulation of RNA editing, subcellular location, stability, and translation shapes immune cell development and immunity. Extensive evidences have now been gathered from few model RBPs, HuR, PTBP1, ZFP36, and Roquin. However, recently developed methodologies for global characterization of protein:RNA interactions suggest the existence of complex RNA regulatory networks in which RBPs co‐ordinately regulate the fate of sets of RNAs controlling cellular pathways and functions. In turn, RNA can also act as scaffolding of functionally related proteins modulating their activation and function. Here we review current knowledge about how RBP‐dependent regulation of RNA shapes our immune system and discuss about the existence of a hidden immune cell epitranscriptome.
This article is categorized under:
RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications
Overview of RNA regulatory mechanisms and their emerging roles in the development and function of lymphocytes, and the immune system.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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