Neutralizing antibody-independent immunity to SARS-CoV-2 in hamsters and hACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein [preprint]

The nucleocapsid (N) and the receptor binding domain (RBD) of the Spike (S) proteins elicit robust antibody and T cell responses either in vaccinated or COVID-19 convalescent individuals. We generated a chimeric protein that comprises the sequences of RBD from S and N antigens (SpiN). SpiN was highly immunogenic and elicited a strong IFNγ response from T cells and high levels of antibodies to the inactivated virus, but no neutralizing antibodies. Importantly, hamsters and the human Angiotensin Convertase Enzyme-2-transgenic mice immunized with SpiN were highly resistant to challenge with the wild type SARS-CoV-2, as indicated by viral load, clinical outcome, lung inflammation and lethality. Thus, the N protein should be considered to induce T-cell-based immunity to improve SARS-CoV-2 vaccines, and eventually to circumvent the immune scape by variants

Contributions of IFN-gamma and granulysin to the clearance of Plasmodium yoelii blood stage

P. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics. Infection with P. yoelii caused extramedullary erythropoiesis, reticulocytosis and expansion of CD8+CD44+CD62L- IFN-gamma-producing T cells that form immune synapses with iRetics. We now provide evidence that MHC-I expression by iRetic is dependent on IFN-gamma-induced transcription of IRF-1, MHC-I and beta2-microglobulin (beta2-m) in erythroblasts. Consistently, CTLs from infected wild type (WT) mice formed immune synapses with iRetics in an IFN-gamma- and MHC-I-dependent manner. When challenged with P. yoelii 17XNL, WT mice cleared parasitemia and survived, while IFN-gamma KO mice remained parasitemic and all died. beta2-m KO mice that do not express MHC-I and have virtually no CD8+ T cells had prolonged parasitemia, and 80% survived. Because mice do not express GNLY, GNLY-transgenic mice can be used to assess the in vivo importance of GNLY. Parasite clearance was accelerated in GNLY-transgenic mice and depletion of CD8+ T cells ablated the GNLY-mediated resistance to P. yoelii. Altogether, our results indicate that in addition to previously described mechanisms, IFN-gamma promotes host resistance to the Retic-tropic P. yoelii 17XNL strain by promoting MHC-I expression on iRetics that become targets for CD8+ cytotoxic T lymphocytes and GNLY

Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva) was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates

Octonion Quantum Chromodynamics

Starting with the usual definitions of octonions, an attempt has been made to establish the relations between octonion basis elements and Gell-Mann \lambda matrices of SU(3)symmetry on comparing the multiplication tables for Gell-Mann \lambda matrices of SU(3)symmetry and octonion basis elements. Consequently, the quantum chromo dynamics (QCD) has been reformulated and it is shown that the theory of strong interactions could be explained better in terms of non-associative octonion algebra. Further, the octonion automorphism group SU(3) has been suitably handled with split basis of octonion algebra showing that the SU(3)_{C}gauge theory of colored quarks carries two real gauge fields which are responsible for the existence of two gauge potentials respectively associated with electric charge and magnetic monopole and supports well the idea that the colored quarks are dyons

Solving Optimization Problems by the Public Goods Game

This document is the Accepted Manuscript version of the following article: Marco Alberto Javarone, ‘Solving optimization problems by the public goods game’, The European Physical Journal B, 90:17, September 2017. Under embargo. Embargo end date: 18 September 2018. The final, published version is available online at doi: https://doi.org/10.1140/epjb/e2017-80346-6. Published by Springer Berlin Heidelberg.We introduce a method based on the Public Goods Game for solving optimization tasks. In particular, we focus on the Traveling Salesman Problem, i.e. a NP-hard problem whose search space exponentially grows increasing the number of cities. The proposed method considers a population whose agents are provided with a random solution to the given problem. In doing so, agents interact by playing the Public Goods Game using the fitness of their solution as currency of the game. Notably, agents with better solutions provide higher contributions, while those with lower ones tend to imitate the solution of richer agents for increasing their fitness. Numerical simulations show that the proposed method allows to compute exact solutions, and suboptimal ones, in the considered search spaces. As result, beyond to propose a new heuristic for combinatorial optimization problems, our work aims to highlight the potentiality of evolutionary game theory beyond its current horizons.Peer reviewedFinal Accepted Versio

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Are sciences essential and humanities elective? Disentangling competing claims for humanities research public value

[EN] Recent policy discourse suggests that arts and humanities research is seen as being less useful to society than other disciplines, notably in science, technology, engineering and mathematics. The paper explores how this assumption s construction has been built and whether it is based upon an unfair prejudice: we argue for a prima facie case to answer in assuming that arts and humanities research s lower societal value. We identify a set of claims circulating in policy circles regarding science, technology, engineering and math- ematics research and arts and humanities research s differences. We find two groups: arts and humanities research is less useful than science, technology, engineering and mathematics, and arts and humanities research is merely differently useful. We argue that empirical analysis is necessary to disentangle which ones are true to assess whether policy-making is being based on rational and evidence-based claims. We argue that debates about public research value should recognise that humanities have different (but equally valid) kinds of societal value.This work was supported by the Spanish Ministry of Education, which funded the PhD research fellowship of Julia Olmos Peñuela through the F.P.U program [AP2007- 01850]. The research fellowship took place in the framework of the HERAVALUE project, Measuring the public value of arts and humanities research, financially supported by the HERA Joint Research Programme, cofunded by AHRC, AKA, DASTI, ETF, FNR, FWF, HAZU, IRCHSS, MHEST, NWO, RANNIS, RCN, VR and The European Community FP7 2007-2013, under the Socio-economic Sciences and Humanities programme. The authors would like to thank the editors and two anonymous referees for their invaluable comments. Any errors or omissions remain the authors’ responsibilitieOlmos-Peñuela, J.; Benneworth, P.; Castro-Martínez, E. (2015). Are sciences essential and humanities elective? Disentangling competing claims for humanities research public value. Arts and Humanities in Higher Education. 14(1):61-78. https://doi.org/10.1177/1474022214534081S617814

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

La cueva de El Sidrón (Borines, Piloña, Asturias): primeros resultados

We expose the preliminary results of the archaeological excavations developed between 2000-2002 in Sidrón's Cave, according to the three main objectives that concern the human fossil record: the anthropological characteristics, how and when they arrived there and the relation between fossils and culture. We conclude preliminarily that the record belongs to Horno Neanderthalensis, archeological remains to the Middle Paleolithic techno-complex, and they are in a secondary position.Se exponen los resultados preliminares de las excavaciones arqueológicas llevadas a cabo en la Cueva de El Sidrón entre 2000 y 2002, de acuerdo con los tres objetivos principales que conciernen al registro fósil humano: las características antropológicas, cómo y cuándo llegaron allí y la relación entre fósiles y cultura. Las primeras conclusiones obtenidas son que los restos humanos pertenecen al Neandertal, que el registro arqueológico corresponde a un tecno-complejo del Paleolítico Medio y que están en posición secundari

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN