The Administration of an α-MSH Analogue Reduces the Serum Release of IL-1α and TNFα Induced by the Injection of a Sublethal Dose of Lipopolysaccharides in the BALB/c Mouse

The injection of α-MSH or of one of its analogues ([Nle₄-D.Phe₇] α-MSH_4–10) reduced, in vivo, the release of two cytokines (IL-1α and TNFα) involved in inflammation. The inflammatory state was induced in BALB/c mice by intraperitoneal injection of a sublethal dose of lipopolysaccharides (LPS). The assay of these cytokines by ELISA showed a reduction of 20% with α-MSH and between 30 and 60% with the α-MSH analogue. The α-MSH or the analogue was administered in one of two ways: intravenously or subcutaneously. The most efficient method seemed to be the subcutaneous one because it improved the activity 10,000 times more than the intravenous method. Moreover, the analogue induced a regression of mortality in the animals treated by the intravenous method. Our results show that α-MSH and one of its analogues inhibit IL-1α and TNFα, and can be used as anti-inflammatory molecules.     

Tuning cellular responses to BMP-2 with material surfaces

Bone morphogenetic protein 2 (BMP-2) has been known for decades as a strong osteoinductive factor and for clinical applications is combined solely with collagen as carrier material. The growing concerns regarding side effects and the importance of BMP-2 in several developmental and physiological processes have raised the need to improve the design of materials by controlling BMP-2 presentation. Inspired by the natural cell environment, new material surfaces have been engineered and tailored to provide both physical and chemical cues that regulate BMP-2 activity. Here we describe surfaces designed to present BMP-2 to cells in a spatially and temporally controlled manner. This is achieved by trapping BMP-2 using physicochemical interactions, either covalently grafted or combined with other extracellular matrix components. In the near future, we anticipate that material science and biology will integrate and further develop tools for in vitro studies and potentially bring some of them toward in vivo applications.     

p11 modulates calcium handling through 5-HT4R pathway in rat ventricular cardiomyocytes

BackgroundThe role of the serotonin receptor 4 (5-HT₄R) pathway in cardiac excitation-contraction coupling (ECC) remains unclear. In the brain, induction of the calcium (Ca²⁺)-binding protein p11 enhances 5-HT₄R translocation and signaling and could therefore be considered as a modulator of the 5-HT₄R pathway in the myocardium. p11 expression is increased by brain-derived neurotrophic factor (BDNF) or antidepressant drugs (imipramine). Thus, we investigated whether p11 regulates the 5-HT₄R pathway in the heart in physiological conditions or under pharmacological induction and the effects on calcium handling.Methods and resultsp11 expression was induced in vivo in healthy Wistar rats by imipramine (10 mg/kg/21 days) and in vitro in left ventricular cardiomyocytes exposed to BDNF (50 ng/ml/8 h). Cell shortening and real-time Ca²⁺ measurements were processed on field-stimulated intact cardiomyocytes with the selective 5-HT₄R agonist, prucalopride (1 μM). Both imipramine and BDNF-induced cardiomyocyte p11 expression unmasked a strong response to prucalopride characterized by an increase of both cell shortening and Ca²⁺ transient amplitude compared to basal prucalopride associated with a high propensity to trigger diastolic Ca²⁺ events. Healthy rats treated with BDNF (180 ng/day/14 days) exhibited a sustained elevated heart rate following a single injection of prucalopride (0.1 mg/kg) which was not observed prior to treatment.ConclusionsWe have identified a novel role for p11 in 5-HT₄R signaling in healthy rat ventricular cardiomyocytes. Increased p11 expression by BDNF and imipramine unraveled a 5-HT₄R-mediated modulation of cardiac Ca²⁺ handling and ECC associated with deleterious Ca²⁺ flux disturbances. Such mechanism could partly explain some cardiac adverse effects induced by antidepressant treatments.     

Binding of B‐cell maturation antigen to B‐cell activating factor induces survival of multiple myeloma cells by activating Akt and JNK signaling pathways

B‐cell maturation antigen (BCMA) is expressed on normal and malignant plasma cells and represents a potential target for therapeutic intervention. In this study, we characterized the mechanism underlying the protein kinase B (Akt) and c‐Jun N‐terminal kinase (JNK) pathways and BCMA interactions in regulating multiple myeloma (MM) cell survival. It was found that the expression levels of B cell‐activating factor (BAFF) and BCMA were increased in MM cells as compared with those in normal controls. The proliferation of U266 cells was induced by recombinant human BAFF (rhBAFF) and could also be decreased by BCMA siRNA. The expression of Bcl‐2 protein was up‐regulated, and Bax protein was down‐regulated after rhBAFF treatment, which could be reversed by BCMA siRNA. Similarly, the protein p‐JNK and p‐Akt were activated by rhBAFF and could be changed by BCMA siRNA. In addition, the BCMA mRNA and protein expression levels were decreased after treatment with Akt and JNK pathway inhibitors. These results suggest that Akt and JNK pathways are involved in the regulation of BCMA. A novel BAFF/BCMA signalling pathway in MM may be a new therapeutic target for MM. Copyright © 2016 John Wiley & Sons, Ltd.     

Portrait of the Patient as a Young Man: An Exploration of the Use of Photographs in Hospital

The display of personal photographs in hospital is a common practice that has yet to be rigorously examined. The photographs displayed are subject to interpretation by the viewer and may lead to misunderstandings or miscommunication if clarification of meaning is not sought. This paper explores a range of possible meanings that the display of photographs in hospital may hold, based on a case study of a 15 year old boy hospitalised with a life threatening illness. Further research is needed into the actual meanings attributed to the display of photographs in hospital by patients and family members.     

Getting to the heart of the matter: CCN2 plays a role in cardiomyocyte hypertrophy

Connective tissue growth factor (CTGF/CCN2) is overexpressed in diabetes. Diabetic rats possess myocardial and cardiomyocyte hypertrophy. In a recent report, Wang and colleagues (Am J Physiol Cell Physiol. 2009 Jul 22. [Epub ahead of print]) show that CCN2 directly mediates cardiomyocyte hypertrophy as well as that induced by high glucose and fatty acid. CCN2 acted via the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy in diabetes.     

Human handling and presentation of a novel object evoke independent dimensions of fear in Japanese quail

Fear is a concept comprising several dimensions, but the nature of these dimensions and the relationships between them remain elusive. To investigate these dimensions in birds, we have used two genetic lines of quail divergently selected on tonic immobility duration, a behavioural index of fear. These two lines differ in their behavioural response to some, but not all, fear-inducing situations. In the present study, we investigated the contribution of human intervention in the differentiation between the two lines. To do this, fear responses towards a novel object were compared between lines in three conditions: (1) in the home cage without any human intervention, (2) in the home cage after human handling and (3) after placement in a novel environment by human handling. Fear behaviour differed between lines after human handling, with or without placement in a novel environment, but presentation of a novel object in the home cage without any human intervention induced similar fear responses in the two lines of quail. These results lead us to suggest that in quail, human intervention evokes a dimension of fear that differs from that evoked by sudden presentation of a novel object, in that these two dimensions may be selected independently.     

Carotenoid synthesis in Streptomyces setonii ISP5395 is induced by the gene crtS, whose product is similar to a sigma factor

In many species of actinomycetes, carotenogenesis can be photoinduced. The capacity to respond to photoinduction is, however unstable and, in various strains of Streptomyces, is lost at a relatively high frequency. In Streptomyces setonii ISP5395, which normally produces no carotenoids, carotenoid-producing mutants can be obtained following protoplast regeneration. We report here the characterization of a gene, crtS, which was isolated from one such mutant and can confer on wild-type S. setonii ISP5395 cells the capacity to synthesize carotenoids. Sequence analysis of crtS reveals an open reading frame, which shows homology to genes that encode alternative sigma factors in Bacillus subtilis. We propose that crtS encodes a sigma factor which is necessary for the expression of a cryptic gene(s) for carotenoid biosynthesis in S. setonii ISP5395.     

Effect of chemical modification of amino groups by fluorescamine on partial reactions of photosynthesis

4-Phenylspiro[furan-2(3H),1-phtalan]3,3′-dione (fluorescamine) was used to covalently modify amino groups of thylakoids. Subsequently its effect on parameters of energy transfer and phosphorylating activity was assessed. While electron transport, the extent of proton uptake, 515 nm change and 9-aminoacridine quench were relatively resistant to such treatment, the functions connected to coupling factor 1, namely ATP formation by acid/base transition, ATPase activity and photophosphorylation were affected much earlier. Photophosphorylation appears to be the most sensitive. The data are interpreted as indicating an involvement of free amino groups in energy transfer.