The complex networks of earth minerals and chemical elements

We study the large-scale organization of the mineral-mineral (MMN) and element-element (EEN) complex networks by analyzing their topological structures. We see that the MMN and EEN are homogeneous, display large cliquishness, small average path length and large average degrees. Most of these networks display uniform degree distribution with the exception of the weighted EEN, which display a power-law degree distribution with exponential tail. All these topological characteristics appear to be consequence of the evolutionary mechanisms giving place to the minerals on Earth mantle, which as a whole display a relatively uniform major element composition. We also study the correlations between some topological network parameters and the abundance of chemical elements in different scenarios. Good correlation is obtained between the weighted degree and the abundance of elements in Earth's crustal rocks

How the parts organize in the whole : a top-downview of molecular descriptors and properties for QSARand drug design

Sometimes the complexity of a system, or the properties derived from it, do depend neither on the individual characteristics of the components of the system nor on the nature of the physical forces that hold them together. In such cases the properties derived from the 'organization' of the system given by the connectivity of its elements can be determinant for explaining the structure of such systems. Here we explore the necessity of accounting for these structural characteristics in the molecular descriptors. We show that graph theory is the most appropriate mathematical theory to account for such molecular features. We review a method (TOPS-MODE) that is able to transform simple molecular descriptors, such as logP, polar surface area, molar refraction, charges, etc., into series of descriptors that account for the distribution of these characteristics (hydrophobicity, polarity, steric effects, etc) across the molecule. We explain the mathematical and physical principles of the TOPS-MODE method and develop three examples covering the description and interpretation of skin sensitisation of chemicals, chromosome aberration produced by organic molecules and drug binding to human serum albumin

Pío del Río-Hortega : A Visionary in the Pathology of Central Nervous System Tumors

Fondo de Investigaciones Sanitarias (11/00185), Redes Temáticasde Investigación Cooperativa en Salud (Ref. RD06/0020/1020).The last 140 years have seen considerable advances in knowledge of central nervous system tumors. However, the main tumor types had already been described during the early years of the twentieth century. The studies of Dr. Pío del Río Hortega have been ones of the most exhaustive histology and cytology-based studies of nervous system tumors. Río Hortega's work was performed using silver staining methods, which require a high level of practical skill and were therefore difficult to standardize. His technical aptitude and interest in nervous system tumors played a key role in the establishment of his classification, which was based on cell lineage and embryonic development. Río Hortega's approach was controversial when he proposed it. Current classifications are not only based on cell type and embryonic lineage, as well as on clinical characteristics, anatomical site, and age

Arrangement and terminations of nerves in the Œsophagus of mammalia

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50112/1/910100403_ftp.pd

Interplay Between ncRNAs and Cellular Communication: A Proposal for Understanding Cell-Specific Signaling Pathways

Cancer; Cell signaling; EpigeneticsCàncer; Comunicació cel·lular; EpigenèticaCáncer; Comunicación celular; EpigenéticaIntercellular communication is essential for the development of specialized cells, tissues, and organs and is critical in a variety of diseases including cancer. Current knowledge states that different cell types communicate by ligand-receptor interactions: hormones, growth factors, and cytokines are released into the extracellular space and act on receptors, which are often expressed in a cell-type-specific manner. Non-coding RNAs (ncRNAs) are emerging as newly identified communicating factors in both physiological and pathological states. This class of RNA encompasses microRNAs (miRNAs, well-studied post-transcriptional regulators of gene expression), long non-coding RNAs (lncRNAs) and other ncRNAs. lncRNAs are diverse in length, sequence, and structure (linear or circular), and their functions are described as transcriptional regulation, induction of epigenetic changes and even direct regulation of protein activity. They have also been reported to act as miRNA sponges, interacting with miRNA and modulating its availability to endogenous mRNA targets. Importantly, lncRNAs may have a cell-type-specific expression pattern. In this paper, we propose that lncRNA-miRNA interactions, analogous to receptor-ligand interactions, are responsible for cell-type-specific outcomes. Specific binding of miRNAs to lncRNAs may drive cell-type-specific signaling cascades and modulate biochemical feedback loops that ultimately determine cell identity and response to stress factors

Clinical application of the HM-1000 image processing for HER2 fluorescence in situ hybridization signal quantification in breast cancer

Breast cancer; HER2 expression; Super-resolution microscopyCàncer de mama; Expressió HER2; Microscòpia de superresolucióCáncer de mama; Expresión HER2; Microscopía de súperresoluciónBackground Accurate quantification of human epidermal growth factor receptor 2 (HER2) gene amplification is important for predicting treatment response and prognosis in patients with breast cancer. Fluorescence in situ hybridization (FISH) is the gold standard for the diagnosis of HER2 status, particularly in cases with equivocal status on immunohistochemistry (IHC) staining, but has some limitations of non-classical amplifications and such cases are diagnosed basing on additional IHC and FISH. This study investigated the clinical utility of a novel super-resolution fluorescence microscopy technique for the better FISH signal visualization and HER2 FISH classification. Methods Fourteen breast cancer tissue samples were retrospectively collected between September 2018 and February 2022, and FISH HER2 signal quantification was evaluated by determining the HER2/chromosome 17 centromere (CEP17) ratio and the number of HER2 signals per nucleus in super- versus conventional-resolution images. Results Super-resolution images maintained the same overall HER2 diagnosis from routine, but HER2 FISH amplification changed negative to monosomy in two cases. Two Letrozole non-response relapses coincided to monosomy samples. The median number of HER2 signals per nucleus was 7.5 in super-resolution images and 4.0 in conventional-resolution images in HER2-positive samples and 2.8 and 2.1 signals per nucleus, respectively, in HER2-negative samples. Conclusions Super-resolution images improved signal visualization, including a significant difference in the number of countable HER2 and CEP17 signals in a single nucleus compared with conventional-resolution images. Increased accuracy of signal quantification by super-resolution microscopy may provide clinicians with more detailed information regarding HER2 FISH status that allows to better FISH classification such as HER2-low samples.This work was supported by Sysmex R&D Center Europe related to reagents and materials

Mesenchymal Stem Cells Delivery in Individuals with Different Pathologies: Multimodal Tracking, Safety and Future Applications

Bioluminescence; Radioiodine therapy; TransdifferentiationBioluminiscencia; Terapia con yodo radiactivo; TransdiferenciaciónBioluminescència; Teràpia amb iode radioactiu; TransdiferenciacióDue to their ease of isolation and their properties, mesenchymal stem cells (MSCs) have been widely investigated. MSCs have been proved capable of migration towards areas of inflammation, including tumors. Therefore, they have been suggested as vectors to carry therapies, specifically to neoplasias. As most of the individuals joining clinical trials that use MSCs for cancer and other pathologies are carefully recruited and do not suffer from other diseases, here we decided to study the safety and application of iv-injected MSCs in animals simultaneously induced with different inflammatory pathologies (diabetes, wound healing and tumors). We studied this by in vitro and in vivo approaches using different gene reporters (GFP, hNIS, and f-Luc) and non-invasive techniques (PET, BLI, or fluorescence). Our results found that MSCs reached different organs depending on the previously induced pathology. Moreover, we evaluated the property of MSCs to target tumors as vectors to deliver adenoviruses, including the interaction between tumor microenvironment and MSCs on their arrival. Mechanisms such as transdifferentiation, MSC fusion with cells, or paracrine processes after MSCs homing were studied, increasing the knowledge and safety of this new therapy for cancer.This research was supported by Instituto de Salud Carlos III (ISCIII) (PI19/01007 and DTS21/00130) and by Fondo Europeo de Desarrollo Regional (Feder) “Una manera de hacer Europa”. We also thank CIBER-BBN and CIBERONC an initiative funded by the VI National R&D&i Plan 2008–2011 financed by the Instituto de Salud Carlos III (ISCIII) with the assistance of the European Regional Development Fund. This study was also partially funded by the Aragon Government (Ph.D. Grant No.r B054/12) and cofounded by Aragon/FEDER 2014–2020 “Building Europe from Aragon”. This research was funded by Spanish Ministerio de Economía y Competitividad and European Regional Development Fund (FEDER) SAF2015-69964-R, RTI2018-099343-B-100 and from the CiberOnc by Instituto de Salud Carlos III (to ADlV)

Tumor analysis of MMR genes in Lynch-like syndrome: Challenges associated with results interpretation

Lynch syndrome; Mismatch repair genes; Tumor testingSíndrome de Lynch; Genes reparadores de desajustes; Pruebas de tumoresSíndrome de Lynch; Gens reparadors de desajustaments; Proves de tumorsBackground Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows. Methods Here, we present the clinical characterization of 229 LLS patients. MMR gene testing was performed in 39 available tumors, and results were analyzed using two variant allele frequency (VAF) thresholds (≥5% and ≥10%). Results and Discussion More biallelic somatic events were identified at VAF ≥ 5% than ≥10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS cases.This study was supported by Carlos III National Health Institute and Ministerio de Ciencia e Innovación and funded by FEDER funds—a way to build Europe [PI19/00553; PID2019-111254RB-I00]; CIBERONC [CB16/12/00234]; and the Government of Catalonia (Secretariat for Universities and Research of the Department of Business and Knowledge, grant 2021SGR01112)