Adult rabbit cardiomyocytes undergo typical hibernation-like dedifferentiation when co-cultured with cardiac fibroblasts.

Objectives: Little is known about the causal factors which induce the typical structural changes accompanying cardiomyocyte dedifferentiation in vivo such as in chronic hibernating myocardium. For identifying important factors involved in cardiomyocyte dedifferentiation, as seen in chronic hibernation, an in vitro model mimicking those morphological changes, would be extremely helpful. Methods: Adult rabbit cardiomyocytes were co-cultured with cardiac fibroblasts. The typical changes induced by this culturing paradigm were investigated using morphometry, electron microscopy and immunocytochemical analysis of several structural proteins, which were used as dedifferentiation markers, i.e., titin, desmin, cardiotin and alpha -smooth muscle actin. Results: Close apposition of fibroblasts with adult rabbit cardiomyocytes induced hibernation-like dedifferentiation, similar to the typical changes seen in chronic hibernation in vivo. Both changes in ultrastructure and in the protein expression pattern of dedifferentiation markers as seen in chronic hibernating myocardium were seen in the co-cultured cardiomyocytes. Conclusion: Hibernation-like changes can be induced by co-culturing adult rabbit cardiomyocytes with fibroblasts. This cellular model can be a valuable tool in identifying and characterizing the pathways involved in the dedifferentiation phenotype in vivo, and already suggests that many of the structural changes accompanying dedifferentiation are not per se dependent on a decreased oxygen availability

Globin-like proteins in Caenorhabditis elegans: in vivo localization, ligand binding and structural properties

Background: The genome of the nematode Caenorhabditis elegans contains more than 30 putative globin genes that all are transcribed. Although their translated amino acid sequences fit the globin fold, a variety of amino-acid substitutions and extensions generate a wide structural diversity among the putative globins. No information is available on the physicochemical properties and the in vivo expression. Results: We expressed the globins in a bacterial system, characterized the purified proteins by optical and resonance Raman spectroscopy, measured the kinetics and equilibria of O2 binding and determined the crystal structure of GLB-1* (CysGH2 T Ser mutant). Furthermore, we studied the expression patterns of glb-1 (ZK637.13) and glb-26 (T22C1.2) in the worms using green fluorescent protein technology and measured alterations of their transcript abundances under hypoxic conditions.GLB-1* displays the classical three-over-three α-helical sandwich of vertebrate globins, assembled in a homodimer associated through facing E- and F-helices. Within the heme pocket the dioxygen molecule is stabilized by a hydrogen bonded network including TyrB10 and GlnE7.GLB-1 exhibits high ligand affinity, which is, however, lower than in other globins with the same distal TyrB10-GlnE7 amino-acid pair. In the absence of external ligands, the heme ferrous iron of GLB-26 is strongly hexacoordinated with HisE7, which could explain its extremely low affinity for CO. This globin oxidizes instantly to the ferric form in the presence of oxygen and is therefore incapable of reversible oxygen binding. Conclusion: The presented data indicate that GLB-1 and GLB-26 belong to two functionally-different globin classes

Electron Transfer Function versus Oxygen Delivery: A Comparative Study for Several Hexacoordinated Globins Across the Animal Kingdom

Caenorhabditis elegans globin GLB-26 (expressed from gene T22C1.2) has been studied in comparison with human neuroglobin (Ngb) and cytoglobin (Cygb) for its electron transfer properties. GLB-26 exhibits no reversible binding for O2 and a relatively low CO affinity compared to myoglobin-like globins. These differences arise from its mechanism of gaseous ligand binding since the heme iron of GLB-26 is strongly hexacoordinated in the absence of external ligands; the replacement of this internal ligand, probably the E7 distal histidine, is required before binding of CO or O2 as for Ngb and Cygb. Interestingly the ferrous bis-histidyl GLB-26 and Ngb, another strongly hexacoordinated globin, can transfer an electron to cytochrome c (Cyt-c) at a high bimolecular rate, comparable to those of inter-protein electron transfer in mitochondria. In addition, GLB-26 displays an unexpectedly rapid oxidation of the ferrous His-Fe-His complex without O2 actually binding to the iron atom, since the heme is oxidized by O2 faster than the time for distal histidine dissociation. These efficient mechanisms for electron transfer could indicate a family of hexacoordinated globin which are functionally different from that of pentacoordinated globins

From fundamental insights to economic viability: valorization of minors from deodorizer distillates

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Connecting the dots between brand experience and brand loyalty: The mediating role of brand personality and brand relationships

This article critically examines consumer–brand relationships from the perspective of interpersonal relationship theory. Specifically, the authors investigate the relationship between brand experience and the two components of brand loyalty, namely purchase brand loyalty and attitudinal brand loyalty. The study also examines the link between brand experience and brand relationship variables, brand trust, brand attachment and brand commitment. In addition, the mediating role of brand personality and brand commitment in the relationship between brand experience and brandloyalty is investigated. Drawing on the results of an empirical cross-brand study from three product categories, the authors demonstrate that brand experience, brand personality and brand relationship variables (brand attachment and brand commitment) all affect the degree to which a consumer is loyal to a brand. On the basis of the findings, the authors offer guidelines to managers on how to build and sustain purchase and attitudinal brand loyalty by enhancing brand experience. The theoretical and managerial significance of the findings together with directions for future research are discussed

The hnRNP family: insights into their role in health and disease

Heterogeneous nuclear ribonucleoproteins (hnRNPs) represent a large family of RNA-binding proteins (RBPs) that contribute to multiple aspects of nucleic acid metabolism including alternative splicing, mRNA stabilization, and transcriptional and translational regulation. Many hnRNPs share general features, but differ in domain composition and functional properties. This review will discuss the current knowledge about the different hnRNP family members, focusing on their structural and functional divergence. Additionally, we will highlight their involvement in neurodegenerative diseases and cancer, and the potential to develop RNA-based therapies

Catalysing sustainable fuel and chemical synthesis

Concerns over the economics of proven fossil fuel reserves, in concert with government and public acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from such combustible carbon, are driving academic and commercial research into new sustainable routes to fuel and chemicals. The quest for such sustainable resources to meet the demands of a rapidly rising global population represents one of this century’s grand challenges. Here, we discuss catalytic solutions to the clean synthesis of biodiesel, the most readily implemented and low cost, alternative source of transportation fuels, and oxygenated organic molecules for the manufacture of fine and speciality chemicals to meet future societal demands

Predictors of burnout, work engagement and nurse reported job outcomes and quality of care: a mixed method study

BACKGROUND: High levels of work-related stress, burnout, job dissatisfaction, and poor health are common within the nursing profession. A comprehensive understanding of nurses’ psychosocial work environment is necessary to respond to complex patients’ needs. The aims of this study were threefold: (1) To retest and confirm two structural equation models exploring associations between practice environment and work characteristics as predictors of burnout (model 1) and engagement (model 2) as well as nurse-reported job outcome and quality of care; (2) To study staff nurses’ and nurse managers’ perceptions and experiences of staff nurses’ workload; (3) To explain and interpret the two models by using the qualitative study findings. METHOD: This mixed method study is based on an explanatory sequential study design. We first performed a cross-sectional survey design in two large acute care university hospitals. Secondly, we conducted individual semi-structured interviews with staff nurses and nurse managers assigned to medical or surgical units in one of the study hospitals. Study data was collected between September 2014 and June 2015. Finally, qualitative study results assisted in explaining and interpreting the findings of the two models. RESULTS: The two models with burnout and engagement as mediating outcome variables fitted sufficiently to the data. Nurse-reported job outcomes and quality of care explained variances between 52 and 62%. Nurse management at the unit level and workload had a direct impact on outcome variables with explained variances between 23 and 36% and between 12 and 17%, respectively. Personal accomplishment and depersonalization had an explained variance on job outcomes of 23% and vigor of 20%. Burnout and engagement had a less relevant direct impact on quality of care (≤5%). The qualitative study revealed various themes such as organisation of daily practice and work conditions; interdisciplinary collaboration, communication and teamwork; staff nurse personal characteristics and competencies; patient centeredness, quality and patient safety. Respondents’ statements corresponded closely to the models’ associations. CONCLUSION: A deep understanding of various associations and impacts on studied outcome variables such as risk factors and protective factors was gained through the retested models and the interviews with the study participants. Besides the softer work characteristics — such as decision latitude, social capital and team cohesion — more insight and knowledge of the hard work characteristic workload is essential

The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration.

Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). DJ-1 plays a role in protection from oxidative stress, but how it functions as an "upstream" oxidative stress sensor and whether this relates to PD is still unclear. Intriguingly, DJ-1 may act as an RNA binding protein associating with specific mRNA transcripts in the human brain. Moreover, we previously reported that the yeast DJ-1 homolog Hsp31 localizes to stress granules (SGs) after glucose starvation, suggesting a role for DJ-1 in RNA dynamics. Here, we report that DJ-1 interacts with several SG components in mammalian cells and localizes to SGs, as well as P-bodies, upon induction of either osmotic or oxidative stress. By purifying the mRNA associated with DJ-1 in mammalian cells, we detected several transcripts and found that subpopulations of these localize to SGs after stress, suggesting that DJ-1 may target specific mRNAs to mRNP granules. Notably, we find that DJ-1 associates with SGs arising from N-methyl-D-aspartate (NMDA) excitotoxicity in primary neurons and parkinsonism-inducing toxins in dopaminergic cell cultures. Thus, our results indicate that DJ-1 is associated with cytoplasmic RNA granules arising during stress and neurodegeneration, providing a possible link between DJ-1 and RNA dynamics which may be relevant for PD pathogenesis