The transcription factor AP-2ɛ regulates CXCL1 during cartilage development and in osteoarthritis

SummaryObjectiveRecently, the transcription factor AP-2ɛ was shown to be a regulator of hypertrophy in cartilage and to be differentially expressed in osteoarthritis (OA). However, the only known target gene of AP-2ɛ up to date is integrin alpha10. To better characterize the function of AP-2ɛ in cartilage we screened for additional target genes.DesignPromoter analysis, ChIP-assays and electrophoretic mobility shift assay were used to characterize the regulation of a new AP-2ɛ target gene in detail.ResultsIn this study, we determined the chemokine CXCL1, already known to be important in osteoarthritis (OA), as a new target gene of AP-2ɛ. We could confirm that CXCL1 is expressed in chondrocytes and significantly over-expressed in OA-chondrocytes. Transient transfection of chondrocytes with an AP-2ɛ expression construct led to a significant increase of the CXCL1 mRNA level in these cells. We identified three potential AP-2 binding sites within the CXCL1 promoter and performed luciferase assays, indicating that an AP-2 binding motif (AP-2.2) ranging from position −135 to −144bp relative to the translation start is responsive to AP-2ɛ. This result was further addressed by site-directed mutagenesis demonstrating that activation of the CXCL1 promoter by AP-2ɛ is exclusively dependent on AP-2.2. Chromatin immunoprecipitation and electromobility shift assays confirmed the direct binding of AP-2ɛ to the CXCL1 promoter in OA-chondrocytes at this site.ConclusionThese findings revealed CXCL1 as a novel target gene of AP-2ɛ in chondrocytes and support the important role of AP-2ɛ in cartilage

COL16A1 (collagen, type XVI, alpha 1)

Review on COL16A1 (collagen, type XVI, alpha 1), with data on DNA, on the protein encoded, and where the gene is implicated

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between cells and their environment. Thereby, the EV cargo is highly dependent on their cellular origin. In this review, we summarize putative mechanisms by which EVs can contribute to musculoskeletal tissue homeostasis, regeneration and disease, in particular matrix remodeling and mineralization, pro-angiogenic effects and immunomodulatory activities. Mesenchymal stromal cells (MSCs) present the most frequently used cell source for EV generation for musculoskeletal applications, and herein we discuss how the MSC phenotype can influence the cargo and thus the regenerative potential of EVs. Induced pluripotent stem cell-derived mesenchymal progenitor cells (iMPs) may overcome current limitations of MSCs, and iMP-derived EVs are discussed as an alternative strategy. In the last part of the article, we focus on therapeutic applications of EVs and discuss both practical considerations for EV production and the current state of EV-based therapies

Plastic localization phenomena in a Mn-alloyed austenitic steel

A 0.5 wt pct C, 22 wt pct Mn austenitic steel, recently proposed for fabricating automotive body structures by cold sheet forming, exhibits plastic localizations (PLs) during uniaxial tensile tests, yet showing a favorable overall strength and ductility. No localization happens during biaxial Erichsen cupping tests. Full-thickness tensile and Erichsen specimens, cut from as-produced steel sheets, were polished and tested at different strain rates. During the tensile tests, the PL phenomena consist first of macroscopic deformation bands traveling along the tensile axis, and then of a series of successive stationary deformation bands, each adjacent to the preceding ones; both types of bands involve the full specimen width and yield a macroscopically observable surface relief. No comparable surface relief was observed during the standard Erichsen tests. Because the stress state is known to influence PL phenomena, reduced-width Erichsen tests were performed on polished sheet specimens, in order to explore the transition from biaxial to uniaxial loading; surface relief lines were observed on a 20-mm-wide specimen, but not on wider ones

Оценка персонала организации на примере Томского филиала ООО «Газпром межрегионгаз Новосибирск»

Объектом исследования в работе является: оценка персонала, как инструмент управления персоналом ООО «Газпром межрегионгаз Новосибирск» филиал в г. Томск. Цель работы – исследование системы оценки персонала и разработка мероприятий по ее совершенствованию для оценки персонала ООО «Газпром межрегионгаз Новосибирск». В процессе исследования проводились: анализ методов оценки персонала в ООО «Газпром межрегионгаз Новосибирск» филиал в г. Томске. В результате исследования: предложены направления совершенствования существующей системы оценки персонала компании, основанной на сочетании KPI и компетенций в компании, которая будет являться более эффективной, достоверной и гибкой, чем балльная система оценки персонала или аттестация персонала с экономической и финансовой точки зрения. Степень внедрения: запланировано внести дополнения и уточнения в существующую систему оценки персонала ООО «Газпром межрегионгаз Новосибирск» филиал в г. Томск. Экономическая эффективность/ значимость работы: В целом внедрение системы оценки персонала основанной на сочетании KPI и компетенций поможет повысить эффективность работы компании на 25-30%, оптимизировать затраты на фонд вознаграждения сотрудников на 15-20%, выстроить эффективную систему стимулирования работников путем разработки системы премирования, систематизировать кадровые процессы.The object of research is the work: evaluation of personnel as human resources management tool of "Gazprom mezhregiongaz Novosibirsk» branch in Tomsk. Objective - research staff appraisal system and the development of measures to improve it for the evaluation of personnel of «Gazprom mezhregiongaz Novosibirsk". The study carried out: analysis of methods for evaluating staff of "Gazprom mezhregiongaz Novosibirsk» branch in Tomsk. As a result of research: proposed ways of improving the existing personnel evaluation system of the company, based on a combination of KPI and competency in the company, which will be more efficient, reliable and flexible than the point system of personnel evaluation and certification of personnel from an economic and financial point of view. Degree of implementation: planned to amend and clarify the existing personnel evaluation system of "Gazprom mezhregiongaz Novosibirsk» branch in Tomsk. Cost-effectiveness / value of the work: In general, the introduction of the staff appraisal system based on a combination of KPI and competencies will help improve business efficiency by 25-30%, to optimize the costs of employee compensation fund by 15-20%, to build an effective system of incentives for workers through the development of a system of bonuses , organize staffing processes

The PAMINO-project: evaluating a primary care-based educational program to improve the quality of life of palliative patients

<p>Abstract</p> <p>Background</p> <p>The care of palliative patients challenges the health care system in both quantity and quality. Especially the role of primary care givers needs to be strengthened to provide them with the knowledge and the confidence of applying an appropriate end-of-life care to palliative patients. To improve health care services for palliative patients in primary care, interested physicians in and around Heidelberg, Germany, are enabled to participate in the community-based program 'Palliative Medical Initiative North Baden (PAMINO)' to improve their knowledge in dealing with palliative patients. The impact of this program on patients' health and quality of life remains to be evaluated.</p> <p>Methods/Design</p> <p>The evaluation of PAMINO is a non-randomized, controlled study. Out of the group of primary care physicians who took part in the PAMINO program, a sample of 45 physicians and their palliative patients will be compared to a sample of palliative patients of 45 physicians who did not take part in the program. Every four weeks for 6 months or until death, patients, physicians, and the patients' family caregivers in both groups answer questions to therapy strategies, quality of life (QLQ-C15-PAL, POS), pain (VAS), and burden for family caregivers (BSFC). The inclusion of physicians and patients in the study starts in March 2007.</p> <p>Discussion</p> <p>Although participating physicians value the increase in knowledge they receive from PAMINO, the effects on patients remain unclear. If the evaluation reveals a clear benefit for patients' quality of life, a larger-scale implementation of the program is considered. </p> <p><b>Trial registration</b>: The study was registered at ‘current controlled trials (CCT)’, registration number: ISRCTN78021852.</p