Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell Functions

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A Novel Xenogeneic Co-Culture System to Examine Neuronal Differentiation Capability of Various Adult Human Stem Cells

Background: Targeted differentiation of stem cells is mainly achieved by the sequential administration of defined growth factors and cytokines, although these approaches are quite artificial, cost-intensive and time-consuming. We now present a simple xenogeneic rat brain co-culture system which supports neuronal differentiation of adult human stem cells under more in vivo-like conditions. Methods and Findings: This system was applied to well-characterized stem cell populations isolated from human skin, parotid gland and pancreas. In addition to general multi-lineage differentiation potential, these cells tend to differentiate spontaneously into neuronal cell types in vitro and are thus ideal candidates for the introduced co-culture system. Consequently, after two days of co-culture up to 12% of the cells showed neuronal morphology and expressed corresponding markers on the mRNA and protein level. Additionally, growth factors with the ability to induce neuronal different iation in stem cells could be found in the media supernatants of the co-cultures. Conclusions: The co-culture system described here is suitable for testing neuronal differentiation capability of numerous types of stem cells. Especially in the case of human cells, it may be of clinical relevance for future cell-based therapeutic applications

The Rule of Law and Economic Growth: Where are We?

Summary It is widely assumed that the rule of law is essential for economic growth. However, the rule of law is clearly a multidimensional concept, encompassing a variety of discrete components from security of person and property rights, to checks on government and control of corruption. We review the theory underlying these different causal mechanisms linking the rule of law to economic growth, and provide an introduction to some outstanding measurement issues. We find that the correlation among different components of the rule of law concept are not tight among developing countries and that some inferences about the effects of property rights protection may not be warranted.rule of law economic growth institutions economic volatility developing countries

The Rule of Law in Post-Conflict Settings: The Empirical Record

This paper analyzes whether and to what extent countries reconstitute the rule of law following civil conflict. Drawing on an original data set of 47 cases in which conflict ended between 1970 and 1999, we find that the cessation of conflict has at best a modest effect on the rule of law. On average, countries revert to the pre-conflict rule-of-law status quo ante. In simple models, rule of law prior to the onset of conflict is the best indicator of post-conflict performance. Analysis of individual cases using structural break analysis shows that the cessation of conflict is not typically associated with an inflection in the rule of law; improvements are modest, take a long time, and fall far short of plausible thresholds for robust rule of law

The Rule of Law and Economic Development

With the enormous expansion of scholarship on this subject, "rule of law" has come to mean different things - ranging from security and order to the operations of courts and the administration of justice. We review the various streams of theoretical and empirical research by academics and practitioners, emphasizing the connections to economic development The core logic is that security of property rights and integrity of contract underpin, respectively, investment and trade, which in turn fuel economic growth and development. However, property rights and contracts rest on institutions, which themselves rest on coalitions of interests. Formal institutions are important, but, particularly in developing countries, informal institutional arrangements play a significant part as well. These considerations lead us to caution against an exaggerated confidence in the ability of development assistance to implant new institutions for the rule of law

(Neuro-)endocrinology of epithelial hair follicle stem cells

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UDP-GlcNAc-1-Phosphotransferase Is a Clinically Important Regulator of Human and Mouse Hair Pigmentation

UDP-GlcNAc-1-phosphotransferase, a product of two separate genes (GNPTAB, GNPTG), is essential for the sorting and transportation of lysosomal enzymes to lysosomes. GNPTAB gene defects cause extracellular missorting of lysosomal enzymes resulting in lysosomal storage diseases, namely mucolipidosis type II and mucolipidosis type III alpha/beta, which is associated with hair discoloration. Yet, the physiological functions of GNPTAB in the control of hair follicle (HF) pigmentation remain unknown. To elucidate these, we have silenced GNPTAB in organ-cultured human HFs as a human ex vivo model for mucolipidosis type II. GNPTAB silencing profoundly inhibited intrafollicular melanin production, the correct sorting of melanosomes, tyrosinase activity, and HMB45 expression in the HF pigmentary unit and altered HF melanocyte morphology in situ. In isolated primary human HF melanocytes, GNPTAB knockdown significantly reduced melanogenesis, tyrosinase activity, and correct tyrosinase protein sorting as well as POMC expression and caused the expected lysosomal enzyme missorting in vitro. Moreover, transgenic mice overexpressing an inserted missense mutation corresponding to that seen in human mucolipidosis type II and mucolipidosis type III alpha/beta showed significantly reduced HF pigmentation, thus corroborating the in vivo relevance of our ex vivo and in vitro findings in the human system. This identifies GNPTAB as a clinically important enzymatic control of human HF pigmentation, likely by directly controlling tyrosinase sorting and POMC transcription in HF melanocytes