Enhanced neurogenic biomarker expression and reinnervation in human acute skin wounds treated by electrical stimulation

Electrical stimulation (ES) is known to promote cutaneous healing; however, its ability to regulate reinnervation remains unclear. First, we show that ES treatment of human acute cutaneous wounds (n = 40) increased reinnervation. Next, to define neurophysiologic mechanisms through which ES affects repair, microarray analysis of wound biopsy samples was performed on days 3, 7, 10, and 14 after wounding. This identified neural differentiation biomarkers TUBB3 (melanocyte development and neuronal marker) and its upstream molecule FIG4 (phosphatidylinositol (3,5)-bisphosphate 5-phosphatase) as significantly up-regulated after ES treatment. To demonstrate a functional ES-TUBB3 axis in cutaneous healing, we showed increased TUBB3 melanocytes and melanogenesis plus FIG4 and nerve growth factor expression, suggesting higher cellular differentiation. In support of this role of ES to regulate neural crest-derived cell fate and differentiation in vivo, knockdown of FIG4 in neuroblastoma cells resulted in vacuologenesis and cell degeneration, whereas ES treatment after FIG4-small interfering RNA transfection enhanced neural differentiation, survival, and integrity. Further characterization showed increased TUBB3 and protein gene product 9.5 Merkel cells during in vivo repair, after ES. We demonstrate that ES contributes to increased expression of neural differentiation biomarkers, reinnervation, and expansion of melanocyte and Merkel cell pool during repair. Targeted ES-assisted acceleration of healing has significant clinical implications

Agri-food business: Global challenges â Innovative solutions

The rise of a western-style middle class in many successful emerging economies like China currently is inducing deep structural changes on agricultural world markets and within the global agri-food business. As a result of both higher incomes and concerns over product safety and quality the global demand for high-quality and safe food products is increasing significantly. In order to meet the new required quality, globally minimum quality standards are rising and private standards emerging. All over the world these developments cause adjustments at the enterprise, chain and market levels. At the same time, the tremendously increasing demand for renewable energy has led to the emergence of a highly promising market for biomass production. This has far-reaching consequences for resource allocation in the agri-food business, for the environment, for the poor in developing countries and for agricultural policy reforms. The challenges increase with ongoing liberalisation, globalisation and standardisation, all of which change trade patterns for agricultural and food commodities, and influence production costs and commodity prices. The objective of the IAMO Forum is to show opportunities as well as risks for all participants of the food economy in the ongoing globalisation process: for small peasants in developing countries, farmers in Europe and globally active food enterprises and retailers. The success of enterprises depends on the ability to find innovative solutions with regard to the organisation of enterprises, chains, and markets, as well as future policy design. Concerning bio-energy strategies has to be identified to combat global warming most efficiently and concurrently attenuate the competition between "tank and table" on farmland. IAMO Forum 2008, as well as this book, would not have been possible without the engagement of many people and institutions. We thank the authors of the papers, as well as the referees. Furthermore we are highly indebted to MARLIES LOHR, NADINE GIEMSA and RONNY RECKE who in an outstanding way contributed to the organisation of the Forum. This is true as well for the IAMO administration, whose work we gratefully acknowledge. Many sponsors has funded the IAMO Forum 2008. We are very grateful to the German Research Foundation (DFG), The Federal Ministry of Food, Agriculture and Consumer Production in Germany, The Ministry of Cultural Affairs of the Federal State Saxony-Anhalt, Germany and last but not least the City of Halle. Further Conference sponsors are the BIONADE Corporation, Gaensefurther Mineral Water, The Wine Growers Association of the Region Saale-Unstrut, Germany, Obsthof am SüÃen See GmbH, Monsanto Company, KWS Saat AG, Sachsen-Anhalt-Tours, Baumkuchen Salzwedel and the Hallesches Brauhaus.Agribusiness, Agricultural and Food Policy, Agricultural Finance, Community/Rural/Urban Development, Industrial Organization, Institutional and Behavioral Economics, International Development, Marketing, Political Economy,

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

Neurocognitive bases of emotion regulation development in adolescence

Emotion regulation is the ability to recruit processes to influence emotion generation. In recent years there has been mounting interest in how emotions are regulated at behavioural and neural levels, as well as in the relevance of emotional dysregulation to psychopathology. During adolescence, brain regions involved in affect generation and regulation, including the limbic system and prefrontal cortex, undergo protracted structural and functional development. Adolescence is also a time of increasing vulnerability to internalising and externalising psychopathologies associated with poor emotion regulation, including depression, anxiety and antisocial behaviour. It is therefore of particular interest to understand how emotion regulation develops over this time, and how this relates to ongoing brain development. However, to date relatively little research has addressed these questions directly. This review will discuss existing research in these areas in both typical adolescence and in adolescent psychopathology, and will highlight opportunities for future research. In particular, it is important to consider the social context in which adolescent emotion regulation develops. It is possible that while adolescence may be a time of vulnerability to emotional dysregulation, scaffolding the development of emotion regulation during this time may be a fruitful preventative target for psychopathology

Adolescent brain development

Adolescence starts with puberty and ends when individuals attain an independent role in society. Cognitive neuroscience research in the last two decades has improved our understanding of adolescent brain development. The evidence indicates a prolonged structural maturation of grey matter and white matter tracts supporting higher cognitive functions such as cognitive control and social cognition. These changes are associated with a greater strengthening and separation of brain networks, both in terms of structure and function, as well as improved cognitive skills. Adolescent-specific sub-cortical reactivity to emotions and rewards, contrasted with their developing self-control skills, are thought to account for their greater sensitivity to the socio-affective context. The present review examines these findings and their implications for training interventions and education

A stable and replicable neural signature of lifespan adversity in the adult brain

Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiological heterogeneity with behavior have yet to be elucidated. Here we estimated normative models of structural brain development based on a lifespan adversity profile in a longitudinal at-risk cohort aged 25 years (n = 169). This revealed widespread morphometric changes in the brain, with partially adversity-specific features. This pattern was replicated at the age of 33 years (n = 114) and in an independent sample at 22 years (n = 115). At the individual level, greater volume contractions relative to the model were predictive of future anxiety. We show a stable neurobiological signature of adversity that persists into adulthood and emphasize the importance of considering individual-level rather than group-level predictions to explain emerging psychopathology

A stable and replicable neural signature of lifespan adversity in the adult brain

Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiological heterogeneity with behavior have yet to be elucidated. Here we estimated normative models of structural brain development based on a lifespan adversity profile in a longitudinal at-risk cohort aged 25 years (n = 169). This revealed widespread morphometric changes in the brain, with partially adversity-specific features. This pattern was replicated at the age of 33 years (n = 114) and in an independent sample at 22 years (n = 115). At the individual level, greater volume contractions relative to the model were predictive of future anxiety. We show a stable neurobiological signature of adversity that persists into adulthood and emphasize the importance of considering individual-level rather than group-level predictions to explain emerging psychopathology

An analysis of the control hierarchy modeling of the CMS detector control system

The supervisory level of the Detector Control System (DCS) of the CMS experiment is implemented using Finite State Machines (FSM), which model the behaviours and control the operations of all the sub-detectors and support services. The FSM tree of the whole CMS experiment consists of more than 30.000 nodes. An analysis of a system of such size is a complex task but is a crucial step towards the improvement of the overall performance of the FSM system. This paper presents the analysis of the CMS FSM system using the micro Common Representation Language 2 (mcrl2) methodology. Individual mCRL2 models are obtained for the FSM systems of the CMS sub-detectors using the ASF+SDF automated translation tool. Different mCRL2 operations are applied to the mCRL2 models. A mCRL2 simulation tool is used to closer examine the system. Visualization of a system based on the exploration of its state space is enabled with a mCRL2 tool. Requirements such as command and state propagation are expressed using modal mu-calculus and checked using a model checking algorithm. For checking local requirements such as endless loop freedom, the Bounded Model Checking technique is applied. This paper discusses these analysis techniques and presents the results of their application on the CMS FSM system