Cognitive Control and Individual Differences in Economic Ultimatum Decision-Making

Much publicity has been given to the fact that people's economic decisions often deviate from the rational predictions of standard economic models. In the classic ultimatum game, for example, most people turn down financial gains by rejecting unequal monetary splits. The present study points to neglected individual differences in this debate. After participants played the ultimatum game we tested for individual differences in cognitive control capacity of the most and least economic responders. The key finding was that people who were higher in cognitive control, as measured by behavioral (Go/No-Go performance) and neural (No-Go N2 amplitude) markers, did tend to behave more in line with the standard models and showed increased acceptance of unequal splits. Hence, the cognitively highest scoring decision-makers were more likely to maximize their monetary payoffs and adhere to the standard economic predictions. Findings question popular claims with respect to the rejection of standard economic models and the irrationality of human economic decision-making

TCR-transgenic T cells and YB-1-based oncolytic virotherapy improve survival in a preclinical Ewing sarcoma xenograft mouse model

BackgroundEwing sarcoma (EwS) is an aggressive and highly metastatic bone and soft tissue tumor in pediatric patients and young adults. Cure rates are low when patients present with metastatic or relapsed disease. Therefore, innovative therapy approaches are urgently needed. Cellular- and oncolytic virus-based immunotherapies are on the rise for solid cancers.MethodsHere, we assess the combination of EwS tumor-associated antigen CHM1319-specific TCR-transgenic CD8+ T cells and the YB-1-driven (i.e. E1A13S-deleted) oncolytic adenovirus XVir-N-31 in vitro and in a xenograft mouse model for antitumor activity and immunostimulatory properties.ResultsIn vitro both approaches specifically kill EwS cell lines in a synergistic manner over controls. This effect was confirmed in vivo, with increased survival using the combination therapy. Further in vitro analyses of immunogenic cell death and antigen presentation confirmed immunostimulatory properties of virus-infected EwS tumor cells. As dendritic cell maturation was also increased by XVir-N-31, we observed superior proliferation of CHM1319-specific TCR-transgenic CD8+ T cells only in virus-tested conditions, emphasizing the superior immune-activating potential of XVir-N-31.ConclusionOur data prove synergistic antitumor effects in vitro and superior tumor control in a preclinical xenograft setting. Combination strategies of EwS-redirected T cells and YB-1-driven virotherapy are a highly promising immunotherapeutic approach for EwS and warrant further evaluation in a clinical setting

Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging

Defects in the DNA repair mechanism nucleotide excision repair (NER) may lead to tumors in xeroderma pigmentosum (XP) or to premature aging with loss of subcutaneous fat in Cockayne syndrome (CS). Mutations of mitochondrial (mt)DNA play a role in aging, but a link between the NER-associated CS proteins and base excision repair (BER)-associated proteins in mitochondrial aging remains enigmatic. We show functional increase of CSA and CSB inside mt and complex formation with mtDNA, mt human 8-oxoguanine glycosylase (mtOGG)-1, and mt single-stranded DNA binding protein (mtSSBP)-1 upon oxidative stress. MtDNA mutations are highly increased in cells from CS patients and in subcutaneous fat of aged Csbm/m and Csa−/− mice. Thus, the NER-proteins CSA and CSB localize to mt and directly interact with BER-associated human mitochondrial 8-oxoguanine glycosylase-1 to protect from aging- and stress-induced mtDNA mutations and apoptosis-mediated loss of subcutaneous fat, a hallmark of aging found in animal models, human progeroid syndromes like CS and in normal human aging

Investigation in vivo and in vitro of oxidative stress and mutations of mitochondrial DNA in the ageing process

Der Alterungsprozess kann in zwei Qualitäten unterteilt werden, intrinsisches und extrinsisches. Während beim intrinsischen Altern auch genannt chronologisches Altern vermehrt genetische und endogene Stoffwechselprozesse eine Rolle spielen, kann beim extrinsischen Altern die ultraviolette Strahlung eine Ursache darstellen. Da es sich bei der Alterung um langwierige Prozesse handelt sind genetische Erkrankungen mit vorzeitiger Alterung wichtige Modellsysteme. Hierzu gehört auch die Erkrankung CockayneSyndrom, die einen Defekt in der Nukleotidexzisionsreparatur aufweist. Am Beispiel des CockayneSyndroms konnten wir und andere zeigen, dass sowohl extrinsische als auch intrinsische Alterungsprozesse beobachtet werden können. Weiter zeigte sich bei dieser Erkrankung, dass Mutationen der mitochondrialen (mt) DNA vermehrt im Alterungsprozess zu beobachten sind und dies vor allem im subkutanen Fett der Haut zu beobachten ist, das alterabhängig reduziert ist. Aus diesen Vorarbeiten heraus haben wir untersucht, wo über den Körper normaler Mäuse verteilt Mutationen der mt DNA in Epidermis, Dermis und subkutanem Fett vermehrt zu beobachten sind und ob dies über oxidativen Stress zum Verlust des subkutanen Fettgewebes führt, wie in Vorarbeiten untersucht. In der Tat konnten wir zeigen, dass im subkutanen Fett gealterter Mäuse mitochondriale Deletionen akkumulieren, die in jungen Mäusen nicht vorhanden sind. Diese Deletionen können auch in Zellkulturen durch den oxidativen Stress einer repetitven UVA-Bestrahlung induziert werden. Weiter war insbesondere an den Extremitäten der Anstieg der mitochondrialen D17Deletion im subkutanen Fett besonders hoch. Insofern liefert diese Arbeit erste Daten wie die Steigerung der D17Deletion über das subkutane Fett des gesamten Körpers verteilt erfolgt. Weitere Untersuchungen sind notwendig um die Ergebnisse im Menschen zu bestätigen.The process of ageing can be divided into two qualities: intrinsic and extrinsic ageing. During intrinsic ageing, also called chronological ageing, genetic and endogenous metabolic processes play a decisive role, while ultraviolet radiation is a cause of extrinsic ageing. Ageing is a tedious process, and genetic diseases with premature ageing are important model-systems. One of these diseases is the Cockayne syndrome, with its defect in nucleotide-excision-repair. The Cockayne syndrome shows us examples of either extrinsic or intrinsic ageing. Furthermore, this disease shows the increase of mitochondrial (mt) DNA mutations in the ageing process especially in the subcutaneous fat, which is reduced due to ageing. Starting from this preliminary work we investigated, the distribution of mitochondrial Deletion in dermal, epidermal, and subcutaneous fat compartment over the whole body and if oxidative stress is the cause of the loss of subcutaneous fat. Indeed we showed accumulation of mitochondrial Deletion in the subcutaneous fat of aged mice. In young mice no deletion occurred. These deletions also can be induced in cell cultures by UVA-irradiation generated oxidative stress. Especially the extremities showed a large increase of mitochondrial D17 deletion in subcutaneous fat. Insofar this work provides data of the distribution and increase of D17 deletion in the subcutaneous fat of the whole body. Further investigation is required to confirm these results in humans

OER Impact Research

Open Oregon Educational Resources sponsored a research group to measure the impact that OER have on teaching and learning. This session will report on preliminary research results from some of the research teams across the state. Columbia Gorge Community College implemented a comparative research project looking at the effects of OER in the classroom. During the winter and spring terms of 2017, two psychology courses - 201A and 202A - were split in half. One half of the students in class used a traditional publisher’s textbook, the other half used OER developed by the instructor. Guided by the question “How does student use of resources differ between traditional learning resources and OER?” Dr. Krummel and librarian John Schoppert will present the data from that research and share our experience and methodology in researching a split classroom. Umpqua Community College is analyzing student success metrics using existing secondary data for courses that adopt OER. Librarian Jennifer Lantrip will present a methodology and preliminary findings comparing course throughput rates (the effect of drop rates, withdraw rates, and final grades) for courses at UCC in which faculty went from assigning commercial textbooks or course material to assigning OER. Lane math instructor Jessica Knoch will present preliminary findings on the effect OER has on student outcomes in both Math 105 and classes subsequent to Math 105. Lane Community College began using OER for all sections of Math 105 in Fall 2015, and we will present data comparing various measures of student success in both Math 105 and Math 243 from before and after that time

Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology.

Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection. Nebulized human mAbs are detectable in nasal, oropharyngeal, and bronchoalveolar lavage (BAL) samples. SARS-CoV-2 mAb treatment significantly reduces levels of SARS-CoV-2 viral RNA and infectious virus in the upper and lower respiratory tracts relative to controls. Reductions in lung and BAL virus levels correspond to reduced BAL inflammatory cytokines and lung pathology. Aerosolized antibody therapy for SARS-CoV-2 could be effective for reducing viral burden and limiting disease severity

Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology

Abstract Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection. Nebulized human mAbs are detectable in nasal, oropharyngeal, and bronchoalveolar lavage (BAL) samples. SARS-CoV-2 mAb treatment significantly reduces levels of SARS-CoV-2 viral RNA and infectious virus in the upper and lower respiratory tracts relative to controls. Reductions in lung and BAL virus levels correspond to reduced BAL inflammatory cytokines and lung pathology. Aerosolized antibody therapy for SARS-CoV-2 could be effective for reducing viral burden and limiting disease severity