Manipulation of Signaling Thresholds in “Engineered Stem Cell Niches” Identifies Design Criteria for Pluripotent Stem Cell Screens

In vivo, stem cell fate is regulated by local microenvironmental parameters. Governing parameters in this stem cell niche include soluble factors, extra-cellular matrix, and cell-cell interactions. The complexity of this in vivo niche limits analyses into how individual niche parameters regulate stem cell fate. Herein we use mouse embryonic stem cells (mESC) and micro-contact printing (µCP) to investigate how niche size controls endogenous signaling thresholds. µCP is used to restrict colony diameter, separation, and degree of clustering. We show, for the first time, spatial control over the activation of the Janus kinase/signal transducer and activator of transcription pathway (Jak-Stat). The functional consequences of this niche-size-dependent signaling control are confirmed by demonstrating that direct and indirect transcriptional targets of Stat3, including members of the Jak-Stat pathway and pluripotency-associated genes, are regulated by colony size. Modeling results and empirical observations demonstrate that colonies less than 100 µm in diameter are too small to maximize endogenous Stat3 activation and that colonies separated by more than 400 µm can be considered independent from each other. These results define parameter boundaries for the use of ESCs in screening studies, demonstrate the importance of context in stem cell responsiveness to exogenous cues, and suggest that niche size is an important parameter in stem cell fate control

Increased Prevalence of Metabolic Syndrome in Patients with Acne Inversa

BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors

Genetic and Pharmacological Inhibition of MicroRNA-92a Maintains Podocyte Cell Cycle Quiescence and Limits Crescentic Glomerulonephritis

Crescentic rapidly progressive glomerulonephritis (RPGN) represents the most aggressive form of acquired glomerular disease. While most therapeutic approaches involve potentially toxic immunosuppressive strategies, the pathophysiology remains incompletely understood. Podocytes are glomerular epithelial cells that are normally growth-arrested because of the expression of cyclin-dependent kinase (CDK) inhibitors. An exception is in RPGN where podocytes undergo a deregulation of their differentiated phenotype and proliferate. Here we demonstrate that microRNA-92a (miR-92a) is enriched in podocytes of patients and mice with RPGN. The CDK inhibitor p57Kip2 is a major target of miR-92a that constitutively safeguards podocyte cell cycle quiescence. Podocyte-specific deletion of miR-92a in mice de-repressed the expression of p57Kip2 and prevented glomerular injury in RPGN. Administration of an anti-miR-92a after disease initiation prevented albuminuria and kidney failure, indicating miR-92a inhibition as a potential therapeutic strategy for RPGN. We demonstrate that miRNA induction in epithelial cells can break glomerular tolerance to immune injury

Совершенствование системы вознаграждения персонала бюджетного учреждения на основе комплексной оценки его деятельности

Объектом исследования является МБОУ 슫СОШ № 18슻 Цель работы - является оценка системы вознаграждения труда персонала бюджетного учреждения, ее оптимизации на основе комплексной оценке его деятельности В процессе исследования проводились способы группировки и сравнения, графические и аналитические методы. В результате исследования были выявлены недостатки и предложен комплекс мер по их устранению. Степень внедрения: сделать систему оплаты труда взаимосвязанной с конкретным результатом каждого работника и учреждения в целом. Область применения: бюджетные учреждения. Экономическая эффективность работы заключается в объективной оценке оплаты труда в бюджетном учреждении и в разработке практических рекомендаций по совершенствованию системы оплаты труда в анализируемом учреждении.The object of study is MBOU "SOSH № 18" Purpose - is to assess the remuneration system of the personnel budget of the institution, its optimization on the basis of a comprehensive assessment of its activities In the process of investigation the methods of grouping and comparison of graphical and analytical methods. The study revealed shortcomings and proposed the complex of measures on their elimination. Level of implementation: to make the wage system is interconnected with the concrete result of each employee and the institution as a whole. Scope: budget companies. Economic efficiency is an objective assessment of remuneration in budgetary institutions and in the development of practical recommendations for improving the system of remuneration in the analyzed institution

Opportunities and risk of using social media for fashion companies

In dieser Arbeit geht es um die Nutzung von Social Media von Modeunternehmen. Die wichtigen Fragestellungen hierbei sind zum einen wie wichtig es für Modeunternehmen ist auf Social Media aktiv zu sein und welche Chancen und Risiken sie bei der Nutzung dieser Art von Marketing haben. Ziel soll es anschließend sein den Modeunternehmen Handlungsempfehlungen geben zu können, um die Chancen optimal zu nutzen und die Risiken zu minimieren. Die Chancen und Risiken wurden mithilfe von Literatur und aktuellen Themen in der Modebranche zusammengefasst und ausgearbeitet. Durch den gesamten Aufbau der Arbeit zeigt sich, wie wichtig die Nutzung von Social Media gerade für Modeunternehmen ist