Cyclic AMP-dependent protein kinase and Ca2+-calmodulin stimulate the formation of polyphosphoinositjdes in a sarcoplasmic reticulum preparation of rabbit heart

AbstractA rabbit heart membrane fraction enriched in sarcoplasmic reticulum was incubated in a reaction mixture containing [γ-32P]ATP. The catalytic subunit of cyclic AMP-dependent protein kinase enhanced the 32P-labelling of both phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate. Ca2+-calmodulin also increased the 32P-incorporation into both polyphosphoinositides. Upon SDS gel-electrophoretic analysis of the membrane proteins, phospholamban was found to be concurrently phosphorylated by the exogenous catalytic subunit as well as by an endogenous Ca2+-calmodulm-dependent protein kinase

Working together: a study on co-produced parenting support services in a Swedish municipality

This article describes an evaluation of co-producing parenting support services in a rural municipality in Sweden. The evaluation looked at the implementation process of a series of positive activities for children and their parents, data from the participating parents and the economy of the project. Methods included interviews, questionnaires, observations and a review of protocols, e-mails, and web pages. Both qualitative and quantitative analytical methods were used. We identified two essential components for successful co-production: 1) The balance between the two actors (public and voluntary sector) in terms of interests, commitment and experienced positive impacts and 2) That both actors remain within their core competencies. Parents were satisfied with the number and quality of the activities and reported improvement in their relationship with their child. Costs for the six sessions provided during the project were 1897 SEK/participant for the orienteering club and 2635 SEK/participant for the riding club

A novel mathematical model describing adaptive cellular drug metabolism and toxicity in the chemoimmune system

Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This "chemoimmune system" consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC) membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on differential equations describing Phase 0-III participants and regulatory elements, and characterized cellular fitness to evaluate toxicity. In spite of the simplifications, the model recapitulates changes associated with acquired drug resistance and allows toxicity predictions under variable protein expression and xenobiotic exposure conditions. Our simulations suggest that multidrug ABC transporters at Phase 0 significantly facilitate the defense function of successive network members by lowering intracellular drug concentrations. The model was extended with a novel toxicity framework which opened the possibility of performing in silico cytotoxicity assays. The alterations of the in silico cytotoxicity curves show good agreement with in vitro cell killing experiments. The behavior of the simplified kinetic model suggests that it can serve as a basis for more complex models to efficiently predict xenobiotic and drug metabolism for human medical applications

ABCG2 Is a Selectable Marker for Enhanced Multilineage Differentiation Potential in Periodontal Ligament Stem Cells.

Periodontal ligament stem cells (PDLSCs) provide an important source for tissue regeneration and may become especially useful in the formation of osteogenic seeds. PDLSCs can be cultured, expanded, and differentiated in vitro; thus, they may be applied in the long-term treatment of the defects in the dental regions. Here we studied numerous potential markers allowing the selection of human PDLSCs with a maximum differentiation potential. We followed the expression of the ATP-binding cassette subfamily G member 2 (ABCG2) membrane transporter protein and isolated ABCG2-expressing cells by using a monoclonal antibody, recognizing the transporter at the cell surface in intact cells. The expression of the ABCG2 protein, corresponding to the so-called side-population phenotype in various tissue-derived stem cells, was found to be a useful marker for the selection of PDLSCs with enhanced osteogenic, chondrogenic, and adipogenic differentiation. These findings may have important applications in achieving efficient dental tissue regeneration by using stem cells from extracted teeth

Promoting positive development among refugee adolescents

Of the estimated 35.3 million refugees around the world (UNHCR, Figures at a Glance, 2022), approximately 50% are children under the age of 18. Refugee adolescents represent a unique group as they navigate developmental tasks in an unstable and often threatening environment or in resettlement contexts in which they often face marginalization. In addition to physiological, social, and psychological changes that mark adolescence, refugee youth often face traumatic experiences, acculturative stress, discrimination, and a lack of basic resources. In this consensus statement, we examine research on refugee adolescents' developmental tasks, acculturative tasks, and psychological adjustment using Suárez-Orozco and colleague's integrative risk and resilience model for immigrant-origin children and youth proposed by Suárez-Orozco et al. Finally, we discuss recommendations-moving from proximal to more distal contexts

In vitro characterization of human mesenchymal stem cells isolated from different tissues with a potential to promote complex bone regeneration

Bone tissue regeneration is a major, worldwide medical need, and several strategies have been developed to support the regeneration of extensive bone defects, including stem cell based bone grafts. In addition to the application of stem cells with high osteogenic potential, it is important to maintain proper blood flow in a bone graft to avoid inner graft necrosis. Mesenchymal stem cells (MSCs) may form both osteocytes and endothelial cells; therefore we examined the combined in vitro osteogenic and endothelial differentiation capacities of MSCs derived from adipose tissue, Wharton’s jelly, and periodontal ligament. Based on a detailed characterization presented here, MSCs isolated from adipose tissue and periodontal ligament may be most appropriate for generating vascularized bone grafts

Functional characterization of the ABCG2 5' non-coding exon variants: Stem cell specificity, translation efficiency and the influence of drug selection.

ABCG2 is a multidrug transporter with wide substrate specificity, and is believed to protect several cell types from various xenobiotics and endobiotics. This "guardian" function is important in numerous cell types and tissue barriers but becomes disadvantageous by being responsible for the multidrug resistance phenotype in certain tumor cells. ABCG2 regulation at the protein level has already been extensively studied, however, regulation at the mRNA level, especially the functional role of the various 5' untranslated exon variants (5' UTRs) has been elusive. In the present work, we describe a comprehensive characterization of four ABCG2 mRNA variants with different exon 1 sequences, investigate drug inducibility, stem cell specificity, mRNA stability, and translation efficiency. Although certain variants (E1B and E1C) are considered as "constitutive" mRNA isoforms, we show that chemotoxic drugs significantly alter the expression pattern of distinct ABCG2 mRNA isoforms. When examining human embryonic stem cell lines, we provide evidence that variant E1A has an expression pattern coupled to undifferentiated stem cell stage, as its transcript level is regulated parallel to mRNAs of Oct4 and Nanog pluripotency marker genes. When characterizing the four exon 1 variants we found no significant differences in terms of mRNA stabilities and half-lives of the isoforms. In contrast, variant E1U showed markedly lower translation efficiency both at the total protein level or regarding the functional presence in the plasma membrane. Taken together, these results indicate that the different 5' UTR variants play an important role in cell type specific regulation and fine tuning of ABCG2 expression