Adipose Tissue as a Major Launch Spot for Circulating Extracellular Vesicle-Carried MicroRNAs Coordinating Tissue and Systemic Metabolism.

Circulating microRNAs (miRNAs), especially transported by extracellular vesicles (EVs), have recently emerged as major new participants in interorgan communication, playing an important role in the metabolic coordination of our tissues. Among these, adipose tissue displays an extraordinary ability to secrete a vast list of EV-carried miRNAs into the circulation, representing new hormone-like factors. Despite the limitations of current methodologies for the unequivocal identification of the origin and destination of EV-carried miRNAs in vivo, recent investigations clearly support the important regulatory role of adipose-derived circulating miRNAs in shaping the metabolism and function of other tissues including the liver, muscle, endocrine pancreas, cardiovascular system, gastrointestinal tract, and brain.

Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality.

Enhancing thermogenic brown adipose tissue (BAT) function is a promising therapeutic strategy for metabolic disease. However, predominantly thermoneutral modern human living conditions deactivate BAT. We demonstrate that selective adipocyte deficiency of the oxygen-sensor HIF-prolyl hydroxylase (PHD2) gene overcomes BAT dormancy at thermoneutrality.

Multi-step regulation of microRNA expression and secretion into small extracellular vesicles by insulin.

Tissues release microRNAs (miRNAs) in small extracellular vesicles (sEVs) including exosomes, which can regulate gene expression in distal cells, thus acting as modulators of local and systemic metabolism. Here, we show that insulin regulates miRNA secretion into sEVs from 3T3-L1 adipocytes and that this process is differentially regulated from cellular expression. Thus, of the 53 miRNAs upregulated and 66 miRNAs downregulated by insulin in 3T3-L1 sEVs, only 12 were regulated in parallel in cells.

Surrogate metamodels from digital image correlation for testing high-performance composite vessels.

In this work, a workflow has been developed for the generation of surrogate metamodels to predict and evaluate failure with a confidence above 95 % in initial service conditions of high-performance cylindrical vessels manufactured in composites by Roll Wrapping technology. Currently, there is no specific testing standardization for this type of vessel and to fill this gap probabilistic numerical models were developed, performed by the Finite Element Method, fed with the material characteristics obtained experimentally by 2D digital image correlation from flat specimens. From the initial numerical model, a surrogate metamodel was generated by stochastic approximations.

Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration.

Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process.

Cardiac Progenitor Cell Exosomal miR-935 Protects against Oxidative Stress.

Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells (CPC). CPC exosomes were first analyzed by LC-MS/MS and compared by RNAseq with exomes of human mesenchymal stromal cells and human fibroblasts to define their differential exosome miRNA repertoire (exo-miR).

Smartvessel: A New Extinguisher Prototype Based on New Materials and IoT Sensors.

Smartvessel is an innovative fire extinguisher prototype supported by new materials and IoT technology that seeks to improve the functionality and efficiency of conventional fire extinguishers. Storage containers for gases and liquids are essential for industrial activity as they enable higher energy density. The main contributions of this new prototype are (i) innovation in the use of new materials that provide lighter and more resistant extinguishers, both mechanically and against corrosion in aggressive environments.

PAHSAs reduce cellular senescence and protect pancreatic beta cells from metabolic stress through regulation of Mdm2/p53.

Senescence in pancreatic beta cells plays a major role in beta cell dysfunction, which leads to impaired glucose homeostasis and diabetes. Therefore, prevention of beta cell senescence could reduce the risk of diabetes. Treatment of nonobese diabetic (NOD) mice, a model of type 1 autoimmune diabetes (T1D), with palmitic acid hydroxy stearic acids (PAHSAs), a novel class of endogenous lipids with antidiabetic and antiinflammatory effects, delays the onset and reduces the incidence of T1D from 82% with vehicle treatment to 35% with PAHSAs.

Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases.

Standalone ring nucleases are CRISPR ancillary proteins, which downregulate the immune response of Type III CRISPR-Cas systems by cleaving cyclic oligoadenylates (cA) second messengers. Two genes with this function have been found within the Sulfolobus islandicus (Sis) genome. They code for a long polypeptide composed by a CARF domain fused to an HTH domain and a short polypeptide constituted by a CARF domain with a 40 residue C-terminal insertion.

A comparative study of the expression of cyclin D1, COX-2, and KI-67 in odontogenic keratocyst vs. ameloblastoma vs. orthokeratinized odontogenic cyst.

Background: Odontogenic keratocysts (OKCs) and orthokeratinized odontogenic Cysts (OOCs) are distinct clinicopathological entities. OKC appears to behave in a way more similar to that of a neoplasm, such as ameloblastoma (AB). The aim of this study is to compare the influence of Ki-67, Cyclin D1 and COX-2 in the diagnosis and pathogenesis of OKC, OOC and AB.

Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR).

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA.

Tissue differences in the exosomal/small extracellular vesicle proteome and their potential as indicators of altered tissue metabolism.

Exosomes/small extracellular vesicles (sEVs) can serve as multifactorial mediators of cell-to-cell communication through their miRNA and protein cargo. Quantitative proteomic analysis of five cell lines representing metabolically important tissues reveals that each cell type has a unique sEV proteome. While classical sEV markers such as CD9/CD63/CD81 vary markedly in abundance, we identify six sEV markers (ENO1, GPI, HSPA5, YWHAB, CSF1R, and CNTN1) that are similarly abundant in sEVs of all cell types.

MicroRNA sequence codes for small extracellular vesicle release and cellular retention.

Exosomes and other small extracellular vesicles (sEVs) provide a unique mode of cell-to-cell communication in which microRNAs (miRNAs) produced and released from one cell are taken up by cells at a distance where they can enact changes in gene expression. However, the mechanism by which miRNAs are sorted into exosomes/sEVs or retained in cells remains largely unknown. Here we demonstrate that miRNAs possess sorting sequences that determine their secretion in sEVs (EXOmotifs) or cellular retention (CELLmotifs) and that different cell types, including white and brown adipocytes, endothelium, liver and muscle, make preferential use of specific sorting sequences, thus defining the sEV miRNA profile of that cell type.

Altered pattern of circulating miRNAs in HIV lipodystrophy perturbs key adipose differentiation and inflammation pathways.

We identified a microRNA (miRNA) profile characterizing HIV lipodystrophy and explored the downstream mechanistic implications with respect to adipocyte biology and the associated clinical phenotype. miRNA profiles were extracted from small extracellular vesicles (sEVs) of HIV-infected individuals with and without lipodystrophic changes and individuals without HIV, among whom we previously showed significant reductions in adipose Dicer expression related to HIV. miR-20a-3p was increased and miR-324-5p and miR-186 were reduced in sEVs from HIV lipodystrophic individuals.

Compression and Strain Predictive Models in Non-Structural Recycled Concretes Made from Construction and Demolition Wastes.

This work aims to investigate different predictive models for estimating the unconfined compressive strength and the maximum peak strain of non-structural recycled concretes made up by ceramic and concrete wastes. The extensive experimental campaign carried out during this research includes granulometric analysis, physical and chemical analysis, and compression tests along with the use of the 3D digital image correlation as a method to estimate the maximum peak strain. The results obtained show that it is possible to accurately estimate the unconfined compressive strength for both types of concretes, as well as the maximum peak strain of concretes made up by ceramic waste.

Peripheral Insulin Regulates a Broad Network of Gene Expression in Hypothalamus, Hippocampus, and Nucleus Accumbens.

The brain is now recognized as an insulin-sensitive tissue; however, the role of changing insulin concentrations in the peripheral circulation in gene expression in the brain is largely unknown. Here, we performed a hyperinsulinemic-euglycemic clamp on 3-month-old male C57BL/6 mice for 3 h. We show that, in comparison with results in saline-infused controls, increases in peripheral insulin within the physiological range regulate expression of a broad network of genes in the brain.

Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma.

Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function.

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in (V600E) and genes characterize PCP and ACP, respectively.

Predictive Models for the Characterization of Internal Defects in Additive Materials from Active Thermography Sequences Supported by Machine Learning Methods.

The present article addresses a generation of predictive models that assesses the thickness and length of internal defects in additive manufacturing materials. These modes use data from the application of active transient thermography numerical simulation. In this manner, the raised procedure is an ad-hoc hybrid method that integrates finite element simulation and machine learning models using different predictive feature sets and characteristics (i.

Wrist Vascular Biometric Recognition Using a Portable Contactless System.

Human wrist vein biometric recognition is one of the least used vascular biometric modalities. Nevertheless, it has similar usability and is as safe as the two most common vascular variants in the commercial and research worlds: hand palm vein and finger vein modalities. Besides, the wrist vein variant, with wider veins, provides a clearer and better visualization and definition of the unique vein patterns.

Oral pulse granuloma and oral pulse granuloma associated with odontogenic keratocyst: Two clinical cases and a review of the literature.

Two cases of oral pulse granuloma (OPG) or vegetable granuloma (VG) are presented, one of which was concomitant with an odontogenic keratocyst (OKC), which is an unusual finding. OKC is characterized by the presence of hyaline rings which include vessels, giant cells, other inflammatory cells and collagen fibres. There are two hypotheses as to its histogenesis: firstly, as a reaction to vegetable matter, such as legumes (thus the nomenclature "pulse" or edible seed) and secondly as a degenerative change in the vessel walls as a result of localized vasculitis.

Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease.

miRNAs can be found in serum and other body fluids and serve as biomarkers for disease. More importantly, secreted miRNAs, especially those in extracellular vesicles (EVs) such as exosomes, may mediate paracrine and endocrine communication between different tissues and thus modulate gene expression and the function of distal cells. When impaired, these processes can lead to tissue dysfunction, aging, and disease.