50 research outputs found

    At the heart of morality lies neuro-visceral integration: lower cardiac vagal tone predicts utilitarian moral judgment

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    To not harm others is widely considered the most basic element of human morality. The aversion to harm others can be either rooted in the outcomes of an action (utilitarianism) or reactions to the action itself (deontology). We speculated that the human moral judgments rely on the integration of neural computations of harm and visceral reactions. The present research examined whether utilitarian or deontological aspects of moral judgment are associated with cardiac vagal tone, a physiological proxy for neuro-visceral integration. We investigated the relationship between cardiac vagal tone and moral judgment by using a mix of moral dilemmas, mathematical modeling and psychophysiological measures. An index of bipolar deontology-utilitarianism was correlated with resting heart rate variability (HRV)—an index of cardiac vagal tone—such that more utilitarian judgments were associated with lower HRV. Follow-up analyses using process dissociation, which independently quantifies utilitarian and deontological moral inclinations, provided further evidence that utilitarian (but not deontological) judgments were associated with lower HRV. Our results suggest that the functional integration of neural and visceral systems during moral judgments can restrict outcome-based, utilitarian moral preferences. Implications for theories of moral judgment are discussed

    Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependent Nuclear Transcription to Antiviral Ribonucleosides

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    Ribonucleoside analogues have potential utility as anti-viral, -parasitic, -bacterial and -cancer agents. However, their clinical applications have been limited by off target effects. Development of antiviral ribonucleosides for treatment of hepatitis C virus (HCV) infection has been hampered by appearance of toxicity during clinical trials that evaded detection during preclinical studies. It is well established that the human mitochondrial DNA polymerase is an off target for deoxyribonucleoside reverse transcriptase inhibitors. Here we test the hypothesis that triphosphorylated metabolites of therapeutic ribonucleoside analogues are substrates for cellular RNA polymerases. We have used ribonucleoside analogues with activity against HCV as model compounds for therapeutic ribonucleosides. We have included ribonucleoside analogues containing 2′-C-methyl, 4′-methyl and 4′-azido substituents that are non-obligate chain terminators of the HCV RNA polymerase. We show that all of the anti-HCV ribonucleoside analogues are substrates for human mitochondrial RNA polymerase (POLRMT) and eukaryotic core RNA polymerase II (Pol II) in vitro. Unexpectedly, analogues containing 2′-C-methyl, 4′-methyl and 4′-azido substituents were inhibitors of POLRMT and Pol II. Importantly, the proofreading activity of TFIIS was capable of excising these analogues from Pol II transcripts. Evaluation of transcription in cells confirmed sensitivity of POLRMT to antiviral ribonucleosides, while Pol II remained predominantly refractory. We introduce a parameter termed the mitovir (mitochondrial dysfunction caused by antiviral ribonucleoside) score that can be readily obtained during preclinical studies that quantifies the mitochondrial toxicity potential of compounds. We suggest the possibility that patients exhibiting adverse effects during clinical trials may be more susceptible to damage by nucleoside analogs because of defects in mitochondrial or nuclear transcription. The paradigm reported here should facilitate development of ribonucleosides with a lower potential for toxicity

    Enzymatically Modified Isoquercitrin Attenuates High-Fat Diet-Induced Obesity

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    Effect of paint baking on the halo ring and mechanical behavior of 30MnB5 hot-stamped steel resistance spot welding joints

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    The present work investigates the effect of paint baking (PB) on the resistance spot welding (RSW) joints of 30MnB5 (1.8 GPa grade) hot-stamped (HS) steel, with focus on the halo ring and fracture behavior under cross-tension loading condition. Microstructural and elemental distribution analyses reveal that severe segregation of alloying elements occurred in the fusion zone (FZ) and that a halo ring with a martensitic structure and a width of about 78 μm was formed in the as-welded joint. The PB process resulted in uniform distribution of alloying elements and recarburization in the halo ring region, thereby drastically decreasing the halo ring width to about 33 μm, which changed the fracture behavior of the joint. Therefore, the as-welded joint failed through the halo ring, while in the PB joint, the fracture propagated partly through the FZ and then redirected through the thickness direction. The PB joints exhibited superior mechanical performance to the as-welded joint, especially the energy absorption

    Application of Ionic Liquids in Hydrometallurgy

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    Ionic liquids, low temperature molten salts, have various advantages manifesting themselves as durable and environmentally friendly solvents. Their application is expanding into various fields including hydrometallurgy due to their unique properties such as non-volatility, inflammability, low toxicity, good ionic conductivity, and wide electrochemical potential window. This paper reviews previous literatures and our recent results adopting ionic liquids in extraction, synthesis and processing of metals with an emphasis on the electrolysis of active/light, rare earth, and platinum group metals. Because the research and development of ionic liquids in this area are still emerging, various, more fundamental approaches are expected to popularize ionic liquids in the metal manufacturing industry

    Analysis of Differentially Expressed Genes in Necrotic Enteritis-infected Fayoumi Chickens using RNA Sequencing

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    We identified and evaluated differentially expressed genes (DEGs) by RNA-Sequencing (RNA-Seq) in the intestinal mucosa of two Fayoumi chicken lines, M5.1 and M15.2, that are affected by necrotic enteritis (NE); these chicken lines share the same genetic background but have different major histocompatibility complexes. RNA-Seq generated over 49 and 40 million reads for lines M5.1 and M15.2, respectively. The alignment of these sequences with the Gallus gallus genome database revealed the expression of more than 14,500 genes in two lines, among which 581, 1270, and 1140 DEGs were detected when lines M15.2 and M5.1 were compared with the control and compared between each other. The analysis of all DEGs using the gene ontology database revealed annotations for 111 biological processes, 32 cellular components, and 17 molecular functions, and KEEG pathway mapping indicated that the DEGs were primarily involved in immunity, responses to various stimuli, and signal transduction. In addition, we analyzed 183 innate immune genes that were differentially expressed in NE-induced chicken lines, including 46 CD molecular genes, 89 immune-related genes, and 13 β-defensin genes with 3 lineage-specific duplications. Taken together, the transcriptional profiles showed that line M5.1 was more resistant to NE than line M15.2 and that differential gene expression patterns were associated with host genetic differences in resistance to NE. qRT-PCR and RNA-Seq analyses showed that all the genes examined had similar responses to NE (correlation coefficient R=0.84 to 0.88, p<0.01) in both lines. To the best of our knowledge, this is the first study that describes NE-induced DEGs using RNA-seq in two lines with different levels of susceptibility to NE. These results will lead to increased insights on NE disease resistance mechanisms and the role of host genes in the control of the host immune response

    Implications of Efficient Hepatic Delivery by Tenofovir Alafenamide (GS-7340) for Hepatitis B Virus Therapy

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    Inside the Peristyle Court of Tuthmosis III, view looking north showing two granite pillars representing Upper and Lower Egypt with a statue of Amun-Re at left; Pylon IV, preceded by obelisks, is the façade of the Ipet-sut. This comprises, from the entrance inwards: a hypostyle hall dominated by the remaining obelisk of Hatshepsut; pylons V and VI; a hall with historical reliefs (the 'Annals of Tuthmosis III'); and a granite shrine of Philip Arrhidaeus (reigned 323-316 BCE) containing a 'solar bark' (the ceremonial boat of the sun-god). The sacred shrine of the Middle Kingdom was originally situated in the 'Middle Kingdom Court' behind an earlier version of the bark shrine. Source: Grove Art Online; http://www.groveart.com/ (accessed 1/19/2008
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