Mediterranean Diet and atherothrombosis biomarkers: a randomized controlled trial

Scope. To assess whether following a Mediterranean diet (MedDiet) improved atherothrombosis biomarkers in high cardiovascular risk individuals. Methods and results. In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, we assessed the 1-year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO; n=120) or nuts (MedDiet-Nuts; n=119) versus a low-fat control diet (n=119). We also studied whether large increments in MedDiet adherence (≥3 score points, relative to compliance decreases) and intake changes in key food items were associated with 1-year differences in biomarkers. We observed differences between 1-year changes in the MedDiet-VOO intervention and control diet on the activity of platelet activating factor acetylhydrolase in HDLs (+7.5% [95% confidence interval: 0.17; 14.8]) and HDL-bound α1-antitrypsin levels (- 6.1% [-11.8; -0.29]), and between the MedDiet-Nuts intervention and the control arm on non-esterified fatty acid concentrations (-9.3% [-18.1; -0.53]). Large MedDiet adherence increments were associated with less fibrinogen (-9.5% [-18.3; -0.60]) and non-esterified fatty acid concentrations (-16.7% [-31.7; -1.74]). Increases in nut, fruit, vegetable, and fatty fish consumption, and decreases in processed meat intake were linked to beneficial changes in atherothrombosis biomarkers. Conclusion. Following a MedDiet improved atherothrombosis biomarkers in high cardiovascular risk individual

Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. © 2012 American Chemical Society

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Concentration Dependent Ion Selectivity in VDAC: A Molecular Dynamics Simulation Study

The voltage-dependent anion channel (VDAC) forms the major pore in the outer mitochondrial membrane. Its high conducting open state features a moderate anion selectivity. There is some evidence indicating that the electrophysiological properties of VDAC vary with the salt concentration. Using a theoretical approach the molecular basis for this concentration dependence was investigated. Molecular dynamics simulations and continuum electrostatic calculations performed on the mouse VDAC1 isoform clearly demonstrate that the distribution of fixed charges in the channel creates an electric field, which determines the anion preference of VDAC at low salt concentration. Increasing the salt concentration in the bulk results in a higher concentration of ions in the VDAC wide pore. This event induces a large electrostatic screening of the charged residues promoting a less anion selective channel. Residues that are responsible for the electrostatic pattern of the channel were identified using the molecular dynamics trajectories. Some of these residues are found to be conserved suggesting that ion permeation between different VDAC species occurs through a common mechanism. This inference is buttressed by electrophysiological experiments performed on bean VDAC32 protein akin to mouse VDAC

Detection of recurrent rearrangement breakpoints from copy number data

<p>Abstract</p> <p>Background</p> <p>Copy number variants (CNVs), including deletions, amplifications, and other rearrangements, are common in human and cancer genomes. Copy number data from array comparative genome hybridization (aCGH) and next-generation DNA sequencing is widely used to measure copy number variants. Comparison of copy number data from multiple individuals reveals recurrent variants. Typically, the interior of a recurrent CNV is examined for genes or other loci associated with a phenotype. However, in some cases, such as gene truncations and fusion genes, the target of variant lies at the boundary of the variant.</p> <p>Results</p> <p>We introduce Neighborhood Breakpoint Conservation (NBC), an algorithm for identifying rearrangement breakpoints that are highly conserved at the same locus in multiple individuals. NBC detects recurrent breakpoints at varying levels of resolution, including breakpoints whose location is exactly conserved and breakpoints whose location varies within a gene. NBC also identifies pairs of recurrent breakpoints such as those that result from fusion genes. We apply NBC to aCGH data from 36 primary prostate tumors and identify 12 novel rearrangements, one of which is the well-known TMPRSS2-ERG fusion gene. We also apply NBC to 227 glioblastoma tumors and predict 93 novel rearrangements which we further classify as gene truncations, germline structural variants, and fusion genes. A number of these variants involve the protein phosphatase PTPN12 suggesting that deregulation of PTPN12, via a variety of rearrangements, is common in glioblastoma.</p> <p>Conclusions</p> <p>We demonstrate that NBC is useful for detection of recurrent breakpoints resulting from copy number variants or other structural variants, and in particular identifies recurrent breakpoints that result in gene truncations or fusion genes. Software is available at <url>http://http.//cs.brown.edu/people/braphael/software.html</url>.</p

Sociopolitical consequences of COVID-19 in the Americas, Europe, and Asia: A multilevel, multicountry investigation of risk perceptions and support for antidemocratic practices

Although different social crises may eventually favor undemocratic and authoritarian forms of governance, at some point, such antidemocratic practices require the support of a significant part of the population to be implemented. The present research investigates how and whether the COVID-19 pandemic might have favoured greater support for antidemocratic governmental practices, on the premise of regaining control and security. Using data from 17 countries (N = 4364) and national-level indicators (i.e., real number of contagions and deaths, and sociopolitical indicators), we test how the risk of contagion and death from COVID-19, along with personal orientations (i.e., social dominance orientation [SDO], right-wing authoritarianism [RWA], and perceived anomie) motivate authoritarian and antidemocratic practices. Results from multilevel models indicate that risk perception and perceptions of political instability predict a wish for stronger leadership, agreement with martial law, and support for a controlling government especially when SDO and RWA are high, while more egalitarian and less conservative people agree less with these authoritarian measures in spite of the levels of risk perception. We discuss the implications for these findings for future research on similar but also dissimilar external events (natural disasters, war, or terror incidents) and the consequences for societies with higher authoritarian tendencies.Fil: Pizarro, José J.. Universidad Católica del Norte; Chile. Universidad del País Vasco; EspañaFil: Cakal, Huseyin. Keele University; Reino UnidoFil: Méndez, Lander. Universidad del País Vasco; EspañaFil: Zumeta, Larraitz N.. Universidad del País Vasco; EspañaFil: Gracia-Leiva, Marcela. Universidad del País Vasco; EspañaFil: Basabe, Nekane. Universidad del País Vasco; EspañaFil: Navarro-Carrillo, Ginés. Universidad de Jaén; EspañaFil: Cazan, Ana Maria. Transilvania University of Brasov; RumaniaFil: Keshavarzi, Saeed. Independent Researcher; IránFil: López López, Wilson. Pontificia Universidad Javeriana; ColombiaFil: Yahiiaiev, Illia. Taras Shevchenko National University of Kyiv; UcraniaFil: Alzugaray Ponce, Carolina. Universidad Santo Tomas; ChileFil: Villagrán, Loreto. Universidad de Concepción; ChileFil: Moyano Díaz, Emilio. Universidad de Talca; ChileFil: Petrović, Nebojša. University of Belgrade; SerbiaFil: Mathias, Anderson. Universidad Autonoma de Coahuila; MéxicoFil: Techio, Elza M.. Universidade Federal da Bahia; BrasilFil: Wlodarczyk, Anna. Universidad Católica del Norte; ChileFil: Alfaro-Beracoechea, Laura. Universidad de Guadalajara; MéxicoFil: Ibarra, Manuel L.. Universidad Nacional Autónoma de México; MéxicoFil: Michael, Andreas. University of Cyprus; ChipreFil: Mhaskar, Sumeet. O.p. Jindal Global University; IndiaFil: Martínez Zelaya, Gonzalo. Universidad Viña del Mar; ChileFil: Bilbao, Marian. Universidad Alberto Hurtado; ChileFil: Delfino, Gisela Isabel. Universidad Pontificia Comillas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carvalho, Catarina L.. Universidad de Porto; PortugalFil: Pinto, Isabel R.. Universidad de Porto; PortugalFil: Mohsin, Falak Zehra. Karachi School Of Business And Leadership; PakistánFil: Espinosa, Agustín. Pontificia Universidad Católica de Perú; PerúFil: Cueto, Rosa María. Pontificia Universidad Católica de Perú; PerúFil: Cavalli, Stefano. Scuola Universitaria Professionale Della Svizzera Italiana; ItaliaFil: da Costa, Silvia. Universidad de Zaragoza; EspañaFil: Amutio, Alberto. Universidad Andrés Bello; Chile. Universidad del País Vasco; EspañaFil: Alonso Arbiol, Itziar. Universidad del País Vasco; EspañaFil: Páez, Darío. Universidad Andrés Bello; Chil

Collective Effervescence, Self-Transcendence, and Gender Differences in Social Well-Being During 8 March Demonstrations

8 March (8M), now known as International Women’s Day, is a day for feminist claims where demonstrations are organized in over 150 countries, with the participation of millions of women all around the world. These demonstrations can be viewed as collective rituals and thus focus attention on the processes that facilitate different psychosocial effects. This work aims to explore the mechanisms (i.e., behavioral and attentional synchrony, perceived emotional synchrony, and positive and transcendent emotions) involved in participation in the demonstrations of 8 March 2020, collective and ritualized feminist actions, and their correlates associated with personal well-being (i.e., affective well-being and beliefs of personal growth) and collective well-being (i.e., social integration variables: situated identity, solidarity and fusion), collective efficacy and collective growth, and behavioral intention to support the fight for women’s rights. To this end, a cross-cultural study was conducted with the participation of 2,854 people (age 18–79; M = 30.55; SD = 11.66) from countries in Latin America (Mexico, Chile, Argentina, Brazil, Peru, Colombia, and Ecuador) and Europe (Spain and Portugal), with a retrospective correlational cross-sectional design and a convenience sample. Participants were divided between demonstration participants (n = 1,271; 94.0% female) and non-demonstrators or followers who monitored participants through the media and social networks (n = 1,583; 75.87% female). Compared with non-demonstrators and with males, female and non-binary gender respondents had greater scores in mechanisms and criterion variables. Further random-effects model meta-analyses revealed that the perceived emotional synchrony was consistently associated with more proximal mechanisms, as well as with criterion variables. Finally, sequential moderation analyses showed that proposed mechanisms successfully mediated the effects of participation on every criterion variable. These results indicate that participation in 8M marches and demonstrations can be analyzed through the literature on collective rituals. As such, collective participation implies positive outcomes both individually and collectively, which are further reinforced through key psychological mechanisms, in line with a Durkheimian approach to collective rituals.Fil: Zumeta, Larraitz N.. Universidad del País Vasco; EspañaFil: Castro Abril, Pablo. Universidad del País Vasco; EspañaFil: Méndez, Lander. Universidad del País Vasco; EspañaFil: Pizarro, José J.. Universidad del País Vasco; EspañaFil: Włodarczyk, Anna. Universidad Católica del Norte; ChileFil: Basabe, Nekane. Universidad del País Vasco; EspañaFil: Navarro Carrillo, Ginés. Universidad de Jaén; EspañaFil: Padoan De Luca, Sonia. Universidad del País Vasco; EspañaFil: da Costa, Silvia. Universidad del País Vasco; EspañaFil: Alonso Arbiol, Itziar. Universidad del País Vasco; EspañaFil: Torres Gómez, Bárbara. Universidad del País Vasco; EspañaFil: Cakal, Huseyin. Keele University; Reino UnidoFil: Delfino, Gisela Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Techio, Elza M.. Universidade Federal da Bahia; BrasilFil: Alzugaray, Carolina. Universidad de Santo Tomas; ChileFil: Bilbao, Marian. Universidad Alberto Hurtado; ChileFil: Villagrán, Loreto. Universidad de Concepción; ChileFil: López López, Wilson. Pontificia Universidad Javeriana; ColombiaFil: Ruiz Pérez, José Ignacio. Universidad Nacional de Colombia; ColombiaFil: Cedeño, Cynthia C.. Universidad Politécnica Salesiana; EcuadorFil: Reyes Valenzuela, Carlos. Universidad Andina Simon Bolivar - Sede Ecuador.; EcuadorFil: Alfaro Beracoechea, Laura. Universidad de Guadalajara; MéxicoFil: Contreras Ibáñez, Carlos César. Universidad Autónoma Metropolitana; MéxicoFil: Ibarra, Manuel Leonardo. Universidad Autónoma del Estado de México; MéxicoFil: Reyes Sosa, Hiram. Universidad Autonoma de Coahuila; MéxicoFil: Cueto, Rosa María. Pontificia Universidad Católica de Perú; PerúFil: Carvalho, Catarina L.. Universidad de Porto; PortugalFil: Pinto, Isabel R.. Universidad de Porto; Portuga

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment