Are All Types of Morality Compromised in Psychopathy

A long-standing puzzle for moral philosophers and psychologists alike is the concept of psychopathy, a personality disorder marked by tendencies to defy moral norms despite cognitive knowledge about right and wrong. Previously, discussions of the moral deficits of psychopathy have focused on willingness to harm and cheat others as well as reasoning about rule-based transgressions. Yet recent research in moral psychology has begun to more clearly define the domains of morality, en- compassing issues of harm, fairness, loyalty, authority, and spiritual purity. Clinical descriptions and theories of psychopathy suggest that deficits may exist primarily in the areas of harm and fairness, although quantitative evidence is scarce. Within a broad sample of participants, we found that scores on a measure of psychopathy predicted sharply lower scores on the harm and fairness subscales of a measure of moral concern, but showed no relationship with authority, and very small relationships with ingroup and purity. On a measure of willingness to violate moral standards for money, psychopathy scores predicted greater willingness to violate moral concerns of any type. Results are further explored via potential mediators and analyses of the two factors of psychopathy

Use of a folding model and in situ spectroscopic techniques for rational formulation development and stability testing of Monoclonal antibody therapeutics

Aggregation is a critical issue that hampers the development of monoclonal antibody therapeutics (Mabs). Traditionally, aggregation is considered a process in which native forms of proteins are transformed into an unstable highly associated form through an intermediate formation step. Here we describe the unfolding of an anti CD40 antibody using a folding model based on Lumry-Eyring nucleated polymerization (LENP) model. This model captures several experimental features of the thermal unfolding of this protein as studied by common in situ biophysical techniques such as circular dichroism, fluorescence spectroscopy and turbidity measurements. According to this model, the unfolding and aggregation of the anti CD40 antibody is determined by several distinct steps that include conformational change(s) to generate aggregation prone states, reversible oligomer formation, nucleation and growth as well as their kinetics and the formation of higher order assemblies/aggregates. Furthermore, the loss of monomer is controlled by both thermodynamic (equilibrium unfolding) and kinetic determinants of the unfolding process. This approach captures both of these rate-limiting steps. It can be concluded that this approach is sensitive to formulation conditions such as protein concentration, changes in buffer conditions, and temperature stress. The potential use of this approach in formulation development and stability testing of Mabs is discussed

Native-like aggregates of Factor VIII (FVIII) are immunogenic von Willebrand Factor deficient and hemophilia A mice

The administration of recombinant Factor VIII (FVIII) is the first line therapy for Hemophilia A (HA), but 25–35% of patients develop an inhibitory antibody response. In general, the presence of aggregates contributes to unwanted immunogenic responses against therapeutic proteins. FVIII has been shown to form both native-like and non-native aggregates. Previously, we showed that non-native aggregates of FVIII are less immunogenic compared to the native protein. Here we investigated the effect of native-like aggregates of FVIII on immunogenicity in HA and von Willebrand Factor knockout (vWF−/−) mice. Mice immunized with native-like aggregates showed significantly higher inhibitory antibody titers compared to animals that received native FVIII. Following re-stimulation in vitro with native FVIII, the activation of CD4+ T cells isolated from mice immunized with native-like aggregates is ~4 fold higher than mice immunized with the native protein. Furthermore, this is associated with increases in the secretion of pro-inflammatory cytokines IL-6 and IL-17 in the native-like aggregate treatment group. The results indicate that the native-like aggregates of FVIII are more immunogenic than native FVIII for both the B cell and T cell responses

Evaluating the effects of nacre on human skin and scar cells in culture

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.Pearl nacre, a biomineralisation product of molluscs, has growing applications in cosmetics, as well as dental and bone restoration, yet a systematic evaluation of its biosafety is lacking. Here, we assessed the biocompatibility of nacre with two human primary dermal fibroblast cell cultures and an immortalised epidermal cell line and found no adverse effects

Mantra: an open method for object and movement tracking

Mantra is a free and open-source software package for object tracking. It is specifically designed to be used as a tool for response collection in psychological experiments and requires only a computer and a camera (a webcam is sufficient). Mantra is compatible with widely used software for creating psychological experiments. In Experiments 1 and 2, we validated the spatial and temporal precision of Mantra in realistic experimental settings. In Experiments 3 and 4, we validated the spatial precision and accuracy of Mantra more rigorously by tracking a computer controlled physical stimulus and stimuli presented on a computer screen

Small intestinal mucosa expression of putative chaperone fls485

<p>Abstract</p> <p>Background</p> <p>Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. <it>fls485 </it>coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze <it>fls48</it>5 expression in human small intestinal mucosa.</p> <p>Methods</p> <p><it>fls485 </it>expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several <it>in situ </it>techniques and usage of newly synthesized mouse monoclonal antibodies.</p> <p>Results</p> <p>fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.</p> <p>Conclusions</p> <p>Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.</p

Transcriptomes and expression profiling of deep-sea corals from the Red Sea provide insight into the biology of azooxanthellate corals

Despite the importance of deep-sea corals, our current understanding of their ecology and evolutionis limited due to difficulties in sampling and studying deep-sea environments. Moreover, a recent reevaluation of habitat limitations has been suggested after characterization of deep-sea corals in the Red Sea, where they live at temperatures of above 20 °C at low oxygen concentrations. To gain further insight into the biology of deep-sea corals, we produced reference transcriptomes and studied gene expression of three deep-sea coral species from the Red Sea, i.e. Dendrophyllia sp., Eguchipsammia fistula, and Rhizotrochus typus. Our analyses suggest that deep-sea coral employ mitochondrial hypometabolism and anaerobic glycolysis to manage low oxygen conditions present in the Red Sea. Notably, we found expression of genes related to surface cilia motion that presumably enhance small particle transport rates in the oligotrophic deep-sea environment. This is the first study to characterize transcriptomes and in situ gene expression for deep-sea corals. Our work offers several mechanisms by which deep-sea corals might cope with the distinct environmental conditions present in the Red Sea. As such, our data provides direction for future research and further insight to organismal response of deep sea coral to environmental change and ocean warming.Tis work was supported by King Abdullah University of Science and Technology (KAUST), baseline funds to CRV and Center Competitive Funding (CCF) Program FCC/1/1973-18-01

Characterization of Multi-Functional Properties and Conformational Analysis of MutS2 from Thermotoga maritima MSB8

The MutS2 homologues have received attention because of their unusual activities that differ from those of MutS. In this work, we report on the functional characteristics and conformational diversities of Thermotoga maritima MutS2 (TmMutS2). Various biochemical features of the protein were demonstrated via diverse techniques such as scanning probe microscopy (SPM), ATPase assays, analytical ultracentrifugation, DNA binding assays, size chromatography, and limited proteolytic analysis. Dimeric TmMutS2 showed the temperature-dependent ATPase activity. The non-specific nicking endonuclease activities of TmMutS2 were inactivated in the presence of nonhydrolytic ATP (ADPnP) and enhanced by the addition of TmMutL. In addition, TmMutS2 suppressed the TmRecA-mediated DNA strand exchange reaction in a TmMutL-dependent manner. We also demonstrated that small-angle X-ray scattering (SAXS) analysis of dimeric TmMutS2 exhibited nucleotide- and DNA-dependent conformational transitions. Particularly, TmMutS2-ADPnP showed the most compressed form rather than apo-TmMutS2 and the TmMutS2-ADP complex, in accordance with the results of biochemical assays. In the case of the DNA-binding complexes, the stretched conformation appeared in the TmMutS2-four-way junction (FWJ)-DNA complex. Convergences of biochemical- and SAXS analysis provided abundant information for TmMutS2 and clarified ambiguous experimental results