The molecular mechanism by which lipid/lipoprotein biosynthesis is regulated in mammals involves a very large number of genes that are subject to multiple levels of regulation. miRNAs are recognized ...contributors to lipid homeostasis at the post-transcriptional level, although the elucidation of their role is made difficult by the multiplicity of their targets and the ability of more miRNAs to affect the same mRNAs. In this study, an evaluation of how miRNA expression varies in organs playing a key role in lipid/lipoprotein metabolism was conducted in control mice and in two mouse models carrying genetic ablations which differently affect low-density lipoprotein metabolism. Mice were fed a lipid-poor standard diet and a diet enriched in cholesterol and saturated fat. The results obtained showed that there are no miRNAs whose expression constantly vary with dietary or genetic changes. Furthermore, it appears that diet, more than genotype, impacts on organ-specific miRNA expression profiles.
Display omitted
•Diet and genotype impact on the mouse miRNome in an organ-specific manner•No miRNAs vary consistently in the organism with different diets or genotype•Dietary lipids are more effective than genotype in driving miRNA expression changes
Cellular physiology; Molecular physiology; Molecular biology; Omics
Regional Student Groups (RSGs) of the International Society for Computational Biology Student Council (ISCB-SC) have been instrumental to connect computational biologists globally and to create more ...awareness about bioinformatics education. This article highlights the initiatives carried out by the RSGs both nationally and internationally to strengthen the present and future of the bioinformatics community. Moreover, we discuss the future directions the organization will take and the challenges to advance further in the ISCB-SC main mission: "Nurture the new generation of computational biologists".
Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms ...of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the 'Disease Module Identification DREAM Challenge', an open competition to comprehensively assess module identification methods across diverse protein-protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology.
Abstract
Induction of specific cellular transitions is of clinical importance, as it allows to revert disease cellular phenotype, or induce cellular reprogramming and differentiation for regenerative ...medicine. Signalling is a convenient way to accomplish such transitions without transfer of genetic material. Here we present the first general computational method that systematically predicts signalling molecules, whose perturbations induce desired cellular transitions. This probabilistic method integrates gene regulatory networks (GRNs) with manually-curated signalling pathways obtained from MetaCore from Clarivate Analytics, to model how signalling cues are received and processed in the GRN. The method was applied to 219 cellular transition examples, including cell type transitions, and overall correctly predicted experimentally validated signalling molecules, consistently outperforming other well-established approaches, such as differential gene expression and pathway enrichment analyses. Further, we validated our method predictions in the case of rat cirrhotic liver, and identified the activation of angiopoietins receptor Tie2 as a potential target for reverting the disease phenotype. Experimental results indicated that this perturbation induced desired changes in the gene expression of key TFs involved in fibrosis and angiogenesis. Importantly, this method only requires gene expression data of the initial and desired cell states, and therefore is suited for the discovery of signalling interventions for disease treatments and cellular therapies.
Cellular differentiation is a complex process where a less specialized cell evolves into a more specialized cell. Despite the increasing research effort, identification of cell-fate determinants ...(transcription factors (TFs) determining cell fates during differentiation) still remains a challenge, especially when closely related cell types from a common progenitor are considered. Here, we develop SeesawPred, a web application that, based on a gene regulatory network (GRN) model of cell differentiation, can computationally predict cell-fate determinants from transcriptomics data. Unlike previous approaches, it allows the user to upload gene expression data and does not rely on pre-compiled reference data sets, enabling its application to novel differentiation systems. SeesawPred correctly predicted known cell-fate determinants on various cell differentiation examples in both mouse and human, and also performed better compared to state-of-the-art methods. The application is freely available for academic, non-profit use at http://seesaw.lcsb.uni.lu.
Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for ...both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics.
MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building.
Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients.
The study was prospectively registered at clinicaltrials.gov (NCT05974475).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present article reports on findings from a survey administered in (country anonymised) to a national representative sample of parents of children aged 0-8 around their sharenting behaviour. We ...first frame sharenting as a complex phenomenon where gendered, generational and agentic matters intertwine and mingle in complex ways. We then report results from a cluster analysis aimed at identifying different sharenting styles reflecting the scale and scope of parents' sharing behaviour among our sample. The relationships between sharenting styles and parents' socio-demographics, as well as parental practices of privacy management are further explored and reported. Altogether, findings provide insights into the experience of sharenting in family life pointing to a variety of sharing practices, while also showing first that sharenting represents a key site of identity performance for young mothers, and then how parents negotiate and manage related issues of agency and privacy.
Aim of the present analysis was to report results of a systematic review of the literature in the setting of patients treated with hypoF PT for benign lesions of the central nervous system (CNS).
The ...methodology complied with the PRISMA recommendations. PubMed, EMBASE and Scopus databases were interrogated in September 2022.
Twelve papers have been selected including patients treated for base of the skull meningiomas (6 papers), vestibular schwannoma (3 papers) and pituitary adenomas (3 papers). Clinical outcomes were evaluated with both radiologic images and clinical parameters. Long-term toxicity was reported in all but one series with an incidence ranging from 2 % to 7 % in patients treated for base of skull meningioma and 1–9 % for schwannoma.
HypoF PT is a safe and effective treatment in selected benign tumors of the CNS. Further dosimetric and clinical comparisons are required to better refine the patients’ selection criteria.
•Clinical data on hypofractionated Proton Therapy are rapidly increasing.•QoL is of particular importance for benign tumor of the CNS.•Hypofractionated PT confirmed to an effective alternative to the photon approach.
PDF
