Detrimental effects of sanctions on human altruism

The existence of cooperation and social order among genetically unrelated individuals is a fundamental problem in the behavioural sciences. The prevailing approaches in biology and economics view cooperation exclusively as self-interested behaviour— unrelated individuals cooperate only if they face economic rewards or sanctions rendering cooperation a self-interested choice. Whether economic incentives are perceived as just or legitimate does not matter in these theories. Fairness-based altruism is, however, a powerful source of human cooperation. Here we show experimentally that the prevailing self- interest approach has serious shortcomings because it overlooks negative effects of sanctions on human altruism. Sanctions revealing selfish or greedy intentions destroy altruistic cooperation almost completely, whereas sanctions perceived as fair leave altruism intact. These findings challenge proximate and ultimate theories of human cooperation that neglect the distinction between fair and unfair sanctions, and they are probably relevant in all domains in which voluntary compliance matters—in relations between spouses, in the education of children, in business relations and organizations as well as in markets.Detrimental effects, sanctions, human altruism

Kiss Kiss Fall In Love: Queer Space, Gender and Sexuality vs. Traditional Systems of Power in Anime

Since its emergence in the late 20th century, anime, or Japanese animation, has grown in increasing global popularity, with strong ties to consumerism and fan culture. Our work will integrate Japanese cultural studies, anime studies, and queer studies as a synthesized lens with which to examine the popular television series, Ouran High School Host Club. Using existing literature on Japanese culture, particularly the club and educational system, as well as queer concepts such as Camp and queer time and space, we will offer a close textual analysis of several episodes of Ouran High School Host Club. Additional lenses include evaluation of the formal elements of animation and common anime motifs. Our paper will examine how the host club space constructs queerness by obscuring heterosexuality and gender conformance through costume and a play with sensuality and eroticism. By focusing on sequences where outside characters, who conform to the traditional power structures, interact with the queer space of the host club, we will observe how the club either transforms or defeats these characters. Through our examination of the conflict between queerness and the systems of power in Ouran High School Host Club, we will indicate further questions for analysing other anime works

Transcriptional Regulation of Energy Homeostasis and Metabolism in the Central Nervous System

The central nervous system (CNS) has been identified as a major site mediating leptin's and insulin's effects on energy and glucose homeostasis. Cell type-specific disruption of key molecules in the CNS has delivered new insights into the signalling pathways influenced by leptin and insulin. Such studies revealed that inactivation of leptin or its receptor leads to massive obesity, closely resembling the situation in patients deficient for these genes. However, more than 95% of obesity account for another yet unsolved mechanism, termed leptin resistance, in which leptin levels are high and signalling components are increasingly activated. In this study the effect of increased basal STAT (signal transducer and activator of transcription) 3 signalling specifically in the anorexigenic proopiomelanocortin (POMC) expressing neurons, as present in obesity, was investigated. Therefore, mice expressing a constitutively active version of STAT3 (STAT3-C) in POMC neurons were characterised (STAT3-CPOMC mice). On normal chow diet, these animals develop obesity as a result of hyperphagia and decreased POMC expression accompanied by central leptin and insulin resistance. This finding coincides with POMC cell-specific, STAT3 mediated upregulation of SOCS3 expression inhibiting both, leptin and insulin signalling. In contrast, upon exposure to high fat diet, food intake and body weight were unaltered in STAT3-CPOMC mice compared to control mice. These experiments directly demonstrate that enhanced basal STAT3 activation in POMC neurons, as present in control mice upon high fat feeding, contributes to the development of hypothalamic leptin and insulin resistance. Moreover, these data also indicate that constitutive STAT3 activation is not sufficient to promote POMC expression, but instead requires simultaneous PI3K dependent release of forkhead box protein O (FOXO) 1 repression. This assumption was verified by a partial rescue of POMC expression and the mild obesity observed in STAT3-CPOMC mice when a dominant negative version of FOXO1 was coexpressed in POMC neurons of these mice. Furthermore, the generation and characterisation of mice expressing a constitutively active version of FOXO1 (FOXO1ADA) selectively in the CNS (FOXO1ADACNS mice) indicated a crucial role for FOXO1 in neuronal survival, since FOXO1ADACNS mice die within two days after birth due to FOXO1ADA-mediated apoptosis of neurons. Taken together, this study highlights the importance of the transcription factors STAT3 and FOXO1 to centrally regulate energy homeostasis and neuronal survival using state of the art techniques

Reorientational Dynamics and Solid-Phase Transformation of Ammonium Dicyanamide into Dicyandiamide

The reorientational dynamics of ammonium dicyanamide ND4[N(C≡N)2] and the kinetics as well as the mechanism of the solid-state isomerization reaction from ammonium dicyanamide into dicyandiamide (N≡C-N=C(NH2)2) was studied by means of 2H and 14N solid-state NMR spectroscopy in a temperature range between 38 and 390 K. Whereas in previous investigations the mechanism of the solid-state transformation was investigated by means of vibrational and magic angle spinning solid-state NMR spectroscopy as well as neutron diffraction, we here present a comprehensive 2H study of the ammonium ion dynamics prior to and during the course of the reaction, thereby highlighting possible cross correlations between dynamics and reactivity involving the ammonium ion. The ND4+ group was found to undergo thermally activated random jumps in a tetrahedral potential, which is increasingly distorted with increasing temperature, giving rise to an asymmetrically compressed or elongated tetrahedron with deviations from the tetrahedral angle of up to 6°. The correlation time follows an Arrhenius law with an activation energy of Ea = 25.8(2) kJ mol-1 and an attempt frequency of τ0-1 = 440(80) THz. The spin−lattice relaxation times were fitted according to a simple Bloembergen−Purcell−Pound type model with a T1 minimum of 4 ms at 230 K. Temperature-dependent librational amplitudes were extracted by line-shape simulations between 38 and 390 K and contrasted with those obtained by neutron diffraction, their values ranging between 5 and 28°. The onset and progress of the solid-phase transformation were followed in situ at temperatures above 372 K and could be classified as a strongly temperature-dependent, heterogeneous two-step reaction proceeding with rapid evolution of ammonia and comparatively slow subsequent reintegration into the solid. On the microscopic level, this correlates with a rapid proton transferpossibly triggered by a coupling between the ammonium ion dynamics and phonon modes on the terahertz time scaleand an essentially decoupled nucleophilic attack of ammonia at the nitrile carbon, giving rise to significantly differing time constants for the two processes

Regulatory assembly of the vacuolar proton pump VOV1-ATPase in yeast cells by FLIM-FRET

We investigate the reversible disassembly of VOV1-ATPase in life yeast cells by time resolved confocal FRET imaging. VOV1-ATPase in the vacuolar membrane pumps protons from the cytosol into the vacuole. VOV1-ATPase is a rotary biological nanomotor driven by ATP hydrolysis. The emerging proton gradient is used for transport processes as well as for pH and Ca2+ homoeostasis in the cell. Activity of the VOV1-ATPase is regulated through assembly / disassembly processes. During starvation the two parts of VOV1-ATPase start to disassemble. This process is reversed after addition of glucose. The exact mechanisms are unknown. To follow the disassembly / reassembly in vivo we tagged two subunits C and E with different fluorescent proteins. Cellular distributions of C and E were monitored using a duty cycle-optimized alternating laser excitation scheme (DCO-ALEX) for time resolved confocal FRET-FLIM measurements.Comment: 8 pages, 3 figure

Intra-rater reliability of determining positions of cervical spinous processes and measuring their relative distances

A reliable detection of bony landmarks of the spine is necessary in order to determine rigid bodies and to reduce the variability of marker placement in a movement laboratory setting. In a first study on the thoracic and lumbar spine, we demonstrated that placing markers on their relative positions between two major landmarks was superior to palpation of specific bony landmarks. The aims of this study were to examine the intra-rater reliability when palpating for spinous processes (SPs) of the second (C2) and seventh cervical vertebrae (C7), to determine the distances between C2 and C7 and the relative position of C7 along the length between C2 and the posterior superior iliac spine (PSIS) level

Colon-Derived Liver Metastasis, Colorectal Carcinoma, and Hepatocellular Carcinoma Can Be Discriminated by the Ca2+-Binding Proteins S100A6 and S100A11

Background: It is unknown, on the proteomic level, whether the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known. Methodology/Principal Findings: In this study, tissue from colon-derived liver metastases (n = 17) were classified, lasermicrodissected, and analysed by ProteinChip arrays (SELDI). The resulting spectra were compared with data for primary colorectal (CRC) and hepatocellular carcinomas (HCC) from our former studies. Of 49 signals differentially expressed in primary HCC, primary CRC, and liver metastases, two were identified by immunodepletion as S100A6 and S100A11. Both proteins were precisely localized immunohistochemically in cells. S100A6 and S100A11 can discriminate significantly between the two primary tumor entities, CRC and HCC, whereas S100A6 allows the discrimination of metastases and HCC. Conclusions: Both identified proteins can be used to discriminate different tumor entities. Specific markers or proteomic patterns for the metastases of different primary cancers will allow us to determine the biological characteristics of metastasis in general. It is unknown how the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumo

Dyslipidemia inhibits Toll-like receptor–induced activation of CD8α-negative dendritic cells and protective Th1 type immunity

Environmental factors, including diet, play a central role in influencing the balance of normal immune homeostasis; however, many of the cellular mechanisms maintaining this balance remain to be elucidated. Using mouse models of genetic and high-fat/cholesterol diet–induced dyslipidemia, we examined the influence of dyslipidemia on T cell and dendritic cell (DC) responses in vivo and in vitro. We show that dyslipidemia inhibited Toll-like receptor (TLR)–induced production of proinflammatory cytokines, including interleukin (IL)-12, IL-6, and tumor necrosis factor-α, as well as up-regulation of costimulatory molecules by CD8α− DCs, but not by CD8α+ DCs, in vivo. Decreased DC activation profoundly influenced T helper (Th) cell responses, leading to impaired Th1 and enhanced Th2 responses. As a consequence of this immune modulation, host resistance to Leishmania major was compromised. We found that oxidized low-density lipoprotein (oxLDL) was the key active component responsible for this effect, as it could directly uncouple TLR-mediated signaling on CD8α− myeloid DCs and inhibit NF-κB nuclear translocation. These results show that a dyslipidemic microenvironment can directly interfere with DC responses to pathogen-derived signals and skew the development of T cell–mediated immunity

Interleukin (IL)-15 and IL-7 Jointly Regulate Homeostatic Proliferation of Memory Phenotype CD8+ Cells but Are Not Required for Memory Phenotype CD4+ Cells

The overall size and composition of the pool of naive and memory T cells are tightly regulated by homeostatic mechanisms. Recent work has shown that homeostasis of naive T cells is controlled by two factors, self-major histocompatibility complex (MHC)/peptide ligands and a cytokine, interleukin (IL)-7. In particular, contact with these two factors is required for naive CD4+ and CD8+ cells to undergo “homeostatic” proliferation, i.e., proliferation induced as a consequence of severe T cell depletion. In contrast to naive T cells, the factors that drive memory T cells to undergo homeostatic proliferation are poorly understood. To address this issue, purified memory phenotype CD4+ and CD8+ cells from normal mice were adoptively transferred into various gene-knockout mice rendered T cell–deficient by sublethal irradiation. Three findings are reported. First, unlike naive T cells, homeostatic proliferation of memory T cells is largely MHC independent. Second, memory CD8+ cells can utilize either IL-7 or IL-15 to undergo homeostatic proliferation; however, in the absence of both IL-7 and IL-15, homeostatic proliferation fails to occur. Third, unlike memory CD8+ cells, homeostatic proliferation of memory CD4+ cells is independent of IL-7 and IL-15 (also IL-4). Thus, the homeostatic proliferation mechanisms that control memory CD8+ cells and memory CD4+ cells are quite distinct