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Cell motility is dependent on a dynamic meshwork of actin filaments that is remodelled continuously. A large number of associated proteins that are severs, cross-links, or caps the filament ends have been identified and the actin cross-linker α-actinin has been implied in several important cellular processes. In Entamoeba histolytica, the etiological agent of human amoebiasis, α-actinin is believed to be required for infection. To better understand the role of α-actinin in the infectious process we have determined the solution structure of the C-terminal calmodulin-like domain using NMR. The final structure ensemble of the apo form shows two lobes, that both resemble other pairs of calcium-binding EF-hand motifs, connected with a mobile linker. [ABSTRACT FROM AUTHOR]

B-cell differentiation is one of the most recognized examples of the progressive lineage commitment that is distinctive for stem cell systems. However, the characteristics of the stage just before a cell becomes restricted to the B-cell lineage are less understood. Using single-cell RNA sequencing technology, Rolink and colleagues are able to define the cellular heterogeneity at this step and challenge our understanding of developmental trajectories in early B-lymphoid development (Alberti-Servera et al, ). [ABSTRACT FROM AUTHOR]

Cripto has been known as an embryonic stem (ES)- or tumor-related soluble/cell membrane protein. In this study, we demonstrated that Cripto has a role as an important regulatory factor for hematopoietic stem cells (HSCs). Recombinant Cripto sustained the reconstitution ability of HSCs in vitro. Flow cytometry analysis uncovered that GRP78, one of the candidate receptors for Cripto, was expressed on a subset of HSCs and could distinguish dormant/myeloid-biased HSCs and active/lymphoid-biased HSCs. Cripto is expressed in hypoxic endosteal niche cells where GRP78+ HSCs mainly reside. Proteomics analysis revealed that Cripto-GRP78 binding stimulates glycolytic metabolism-related proteins and results in lower mitochondrial potential in HSCs. Furthermore, conditional knockout mice for HIF-1α, a master regulator of hypoxic responses, showed reduced Cripto expression and decreased GRP78+ HSCs in the endosteal niche area. Thus, Cripto-GRP78 is a novel HSC regulatory signal mainly working in the hypoxic niche. [ABSTRACT FROM AUTHOR]

The process of measuring in software engineering has already been standardized in the ISO/IEC 15939 standard, where activities related to identifying, creating, and evaluating of measures are described. In the process of measuring software entities, however, an organization usually needs to create custom measurement systems, which are intended to collect, analyze, and present data for a specific purpose. In this paper, we present a proven industrial process for developing measurement systems including the artifacts and deliverables important for a successful deployment of measurement systems in industry. The process has been elicited during a case study at Ericsson and is used in the organization for over 3 years when the paper was written. The process is supported by a framework that simplifies the implementation of the measurement systems and shortens the time from the initial idea to a working measurement system by the factor of 5 compared with using a standard development process not tailored for measurement systems. Copyright © 2010 John Wiley & Sons, Ltd. The best measurement systems are those that address the direct information needs of their stakeholders. In this paper we present how such custom measurement systems can be easily developed and fully automated without the need for expensive tools, based on our experiences from Ericsson. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The transforming growth factor (TGF)-β superfamily of growth factors, including the TGF-βs, activins, and bone morphogenetic proteins (BMPs), provide cells with a broad spectrum of regulatory signals through the intracellular Smad pathway. Since loss-of-function studies of a majority of the TGF-β superfamily members result in embryonic lethality, much of our current knowledge of the TGF-β superfamily's role in hematopoiesis is generated from studies performed in vitro, or in very early stages of embryonic development. TGF-β is well documented as a potent inhibitor of hematopoietic stem cell (HSC) proliferation in vitro, while its role in vivo is largely unknown. BMP signaling is crucial for the initiation of hematopoiesis in the developing embryo, although its role in adult hematopoiesis remains elusive. More recently we and others have used conditional knockout models to unravel the role of several components of TGF-β family signaling in adult hematopoiesis. Here we review the currently known functions for the major factors of this signaling family in embryonic and adult hematopoietic regulation and discuss the context dependency and complexity that permeate this regulation. [ABSTRACT FROM AUTHOR]

Enrichment of diet and culture media with the polyunsaturated fatty acid docosahexaenoic acid has been found to reduce the amyloid burden in mice and lower amyloid-β (Aβ) levels in both mice and cultured cells. However, the direct interaction of polyunsaturated fatty acids, such as docosahexaenoic acid, with Aβ, and their effect on Aβ aggregation has not been explored in detail. Therefore, we have investigated the effect of docosahexaenoic acid, arachidonic acid and the saturated fatty acid arachidic acid on monomer oligomerization into protofibrils and protofibril fibrillization into fibrils in vitro, using size exclusion chromatography. The polyunsaturated fatty acids docosahexaenoic acid and arachidonic acid at micellar concentrations stabilized soluble Aβ42 wild-type protofibrils, thereby hindering their conversion to insoluble fibrils. As a consequence, docosahexaenoic acid sustained amyloid-β-induced toxicity in PC12 cells over time, whereas Aβ without docosahexaenoic acid stabilization resulted in reduced toxicity, as Aβ formed fibrils. Arachidic acid had no effect on Aβ aggregation, and neither of the fatty acids had any protofibril-stabilizing effect on Aβ42 harboring the Arctic mutation (AβE22G). Consequently, AβArctic-induced toxicity could not be sustained using docosahexaenoic acid. These results provide new insights into the toxicity of different Aβ aggregates and how endogenous lipids can affect Aβ aggregation. [ABSTRACT FROM AUTHOR]

Retrospective estimations of dental care costs of periodontal and prosthodontic treatment and evaluation of oral health in 37 patients with advanced periodontal disease were carried out. Measures of their subjective evaluation of oral health 7-10 yr after the treatment are presented as a health profile and as indices in single numbers. The relations between oral health as an index and the dimensions in the health profile are analyzed. Dental care costs for treatment in the mandible was SEK 35,550, for the maxilla SEK 45,380 and for both jaws SEK 74,230. After the treatment oral health as well as general health were in excess of 75 on a 0 to 100 scale. Chewing ability, comfort and aesthetics were the variables found to significantly affect the subjective oral health. Oral health in terms of periodontal and prosthodontic conditions was maintained over the observation period. [ABSTRACT FROM AUTHOR]

Twenty-six Swedish dental health care clinics participating in the intervention study "Evaluation of caries preventive measures" have been analysed with focus on costs, with the aim of demonstrating techniques suitable for evaluating direct dental care costs and also finding out whether charges are acceptable as a proxy for real costs. Three different approaches to calculating unit costs are discussed: average treatment time cost and two methods of different allocation of overhead cost. Average treatment time cost shows treatment time cost regardless of who (dentist, dental hygienist or nurse) provides the dental care. The other two methods reflect both the differences of treatment costs depending on practitioners' skill level and competence (salary) and the methods of handling overhead cost allocation. Our conclusions ate that the proposed methods seem useful for evaluating costs in cost-effectiveness and cost-benefit analysis. The alternative to average treatment time cost or unit time cost depends on what data is available and the perspective of the analysis. This study also concludes that charges are not sufficient as an alternative to a more detailed cost evaluation, at least not in Swedish public dental health care, since charges do not cover costs. [ABSTRACT FROM AUTHOR]