Heterogeneity in astrocyte responses after acute injury in vitro and in vivo

Astrocytes present a major population of glial cells in the adult mammalian brain. The heterogeneity of astrocytes in different regions of the healthy central nervous system (CNS) and their physiological functions are well understood. In contrast, rather little is known about the diversity of astrocyte reactions under pathological conditions. After CNS injury the reaction of astrocytes, also termed ‘reactive astrogliosis’, is characterized by morphological and molecular changes such as hypertrophy, polarization, migration and up-regulation of intermediate filaments. So far, it was unknown whether all astrocytes undergo these changes, or whether only specific subpopulations of reactive astrocytes possess special plasticity. Since some quiescent, postmitotic astrocytes in the cortical gray matter apparently de-differentiate and re-enter the cell cycle upon injury, reactive astrocytes have the ability to acquire restrictive stem cell potential. However, the mechanisms leading to increased astrocyte numbers after acute injury, e.g. proliferation and migration, had not been investigated live in vivo. For the first time, recently established in vivo imaging using 2-photon laser scanning microscopy (2pLSM) allowed to follow single GFP-labeled astrocytes for days and weeks after cortical stab wound injury. Tracing morphological changes during the transition from a quiescent to reactive state, these live observations revealed a heterogeneous behavior of reactive astrocytes depending on the lesion size. Different subsets of astrocytes either became hypertrophic, polarized and/ or divided, but never migrated towards the injury. Intriguingly, the lack of astrocyte migration was not only contradictory to what had been predicted based on in vitro and in situ studies, but was also in stark contrast to the motility of other glial cells. Additionally, live imaging provided first evidence that only a small subset of reactive astrocytes in juxtavascular positions re-gains proliferative capacity after injury. While astrocyte proliferation was affected by conditional deletion of RhoGTPase Cdc42 – a key regulator of cell polarity –, the vascular niche was preserved, indicating that juxtavascular astrocytes are uniquely suited for proliferation after injury. Following the behavior of cdc42-deficient astrocytes by live imaging using an in vitro scratch wound assay, cell-autonomous effects including disturbed polarity and impaired directional migration confirmed a crucial role of Cdc42 signaling in reactive astrocytes after acute injury in vitro and in vivo. These novel insights revise current concepts of reactive astrocytes involved in glial scar formation by assigning regenerative potential to a minor pool of proliferative, juxtavascular astrocytes, and suggesting specific functions of different astrocyte subsets after CNS trauma.Astrozyten bilden die größte Gruppe von Gliazellen im Gehirn erwachsener Säugetiere. Die Heterogenität von Astrozyten in verschiedenen Regionen des zentralen Nervensystems (ZNS), sowie deren physiologischen Funktionen sind relativ gut untersucht. Hingegen ist die Diversität der astrozytären Reaktion unter pathologischen Bedingungen bis jetzt wenig verstanden. In Folge einer Verletzung des ZNS reagieren Astrozyten mit bestimmten molekularen und morphologischen Veränderungen wie Hypertrophie, Polarisierung, Wanderung und Hochregulation bestimmter Intermediärfilamente. Diese Veränderungen werden insgesamt als „reaktive Gliose“ zusammengefasst. Darüber hinaus scheinen nach akuten Gehirnverletzungen einige reife, postmitotische Astrozyten in der Großhirnrinde zu de-differenzieren, in den Zellzyklus einzutreten und begrenzt Stammzelleigenschaften zu erlangen. Es ist bisher nicht bekannt, ob alle Astrozyten auf Verletzungen reagieren, oder ob Teilpopulationen verschiedener Plastizität existieren. Weiterhin sind die Mechanismen, die zum Anstieg von Astrozyten nach akuter Verletzung führen, z.B. Proliferation und Wanderung, in vivo bislang nicht verstanden. Deshalb wurde hier erstmals das Verhalten von Fluoreszenz-markierten Astrozyten im Gehirn der Maus nach akuter kortikaler Verletzung live über einen längeren Zeitraum mittels 2-Photonenmikroskopie untersucht. Die Beobachtungen zeigten morphologische Veränderungen und heterogene Verhaltensmuster reaktiver Astrozyten, d.h. hypertrophe, polarisierende und sich teilende Astrozyten in Abhängigkeit von der Läsionsgröße. Im Gegensatz zu in vitro und in situ Studien, sowie bekannter Motilität anderer Typen von Gliazellen, wurde die Wanderung von Astrozyten zum Ort der Verletzung in vivo nicht beobachtet. Allerdings wurde entdeckt, dass sich nur eine kleine Teilpopulation von Astrozyten teilt, und diese vorrangig in direktem Kontakt mit Blutgefäßen (juxtavaskulär) liegt. Selbst nach Verlust der RhoGTPase Cdc42 – einem Schlüsselfaktor für Zellpolarität –, der zu einem Proliferationsdefekt der Astrozyten führte, blieb die vaskuläre Nische erhalten. In einem in vitro Verletzungsmodell zeigten cdc42-defizienten Astrozyten Polaritätsdefekte, verbunden mit desorientierter Wanderung und verminderter Zellteilung. Schlussfolgernd, spielen Cdc42-vermittelte Signalwege eine wichtige Rolle für die Reaktion von Astrozyten auf eine akute Verletzung in vitro und in vivo. Die hier präsentierte Studie trägt bedeutend zum Verständnis reaktiver Astrozyten in Bezug auf deren Rolle in der Narbenbildung und Regeneration von geschädigtem Hirngewebe bei. Insbesondere wurden neue Erkenntnisse über verschiedene Teilpopulationen von Astrozyten mit vermutlich unterschiedlichen Funktionen gewonnen. Hierbei konnte vor allem den juxtavaskulär proliferierenden Astrozyten nach einer traumatischen Hirnverletzung hohe Plastizität zugesprochen werden

What is Men's Health? A definition

© 2017 The Dougmar Publishing Group. Target of the study Men's Health is increasingly coming into force within health research, epidemiology, health care organisation, and health policy. Over the past 10-15 years the EU Men's Health Report and reports within some countries have publicised problems of health in men. A starting point for the study of men's health is the defi nition of "Men's Health". A group of German experts in the fi eld of men's health has taken on this task. Methodology A literature review in international and national databases was performed for the years 1990-2014 by selected MeSH terms and for "experts in men's health". Further research concerned "grey literature" in Germany, especially health reports and web pages. This was followed by a conference of experts to defi ne "Men's Health" using a modifi ed Delphi method according to W. Zinn. From the expert group, minimum criteria for a defi nition of "Men's Health", which must comply with the new defi nition of men's health, were created and discussed. The fi nal defi nition was created in the third round of the Delphi method. Results The international literature review yielded seven defi nitions of "Men's Health" in the English literature and fi ve defi nitions in the German literature including within the "grey" literature. The expert group identifi ed seven minimum criteria and fi fteen relevant topics that were needed for a strong defi nition, of which, by weighting, eight criteria were considered relevant for a new defi nition. None of the existing defi nitions could fulfi l these eight criteria. Therefore, in the next step of the expert group a new defi nition "Men's Health" was elaborated. The defi nition has reference to the WHO concept of "health" and includes dimensions of health and disease, risk and protective factors that require special prevention and care services for all phases of life. All participants in the expert group agreed on the defi nition developed. Conclusions The defi nition of Men's Health is a basis for further research and practice to improve men's health in Germany and other countries

Could Formononetin of Red Clover (\u3cem\u3eTrifolium pratense\u3c/em\u3e L.) be Enhanced by Phosphorus and Arbuscular Mycorrhizal Fungi Management?

Red clover is a forage legume of importance in the world with limited persistency; in Chile this is due mainly to the root borer (Hylastinus obscurus Marsham) infestation. Our previous studies have shown that there is a strong relationship between the root borer and the formononetin content in roots of the plants; therefore, studying factors that enhance the concentration of formononetin in the plant could help to decrease the negative effect of the root borer. The purpose of this research was to assess the relationship between phosphorus availability (P) in the soil interacting with arbuscular mycorrhizal fungi (AMF) over the concentration of formononetin in shoots and roots of red clover. One trial was carried out in a growth chamber at Carillanca Research Center, INIA-Chile, using 6.000 cc pots filled with an Andisol soil. Three levels of soil available phosphorus (10 ppm Olsen-P; 17 ppm Olsen-P; 24 ppm Olsen-P) and two levels of arbuscular mycorrhizal fungi (inoculated and non-inoculated with a commercial mixture) were implemented in a factorial arrangement in a completely randomized design. Soil water was maintained between 50 and 100% of the readily available soil water (RAW) by weighting each pot. Formononetin concentration of shoots and roots was evaluated in two sampling dates by extracting with a methanol solution and relative quantifications based on HPLC. Shoot and root biomass were affected significantly by P and not by AMF, being higher with increased P; however, formononetin concentration was higher with reduced P. On the other hand, there was a significant increase of formononetin concentration both in shoots and roots in the treatments inoculated with AMF. The medium level of P (17 ppm) with AMF inoculation shows a good compromise between biomass production and formononetin concentration

Formononetin of Red Clover (\u3ci\u3eTrifolium pratense\u3c/i\u3e L.) as Affected by Water Availability

Red clover is a valuable legume in the world. Among the biotic factors limiting persistence of the species in Chile is the root borer Hylastinus obscurus (Marsham). Our previous studies have shown a negative effect of formononetin content of the plant on the root borer fitness The purpose of this research was to assess the relationship between water availability and formononetin concentration. Two independent growth chamber experiments were established at Carillanca Research Center, INIA-Chile in order to study the effect of water availability on formononetin concentration in the aerial and root parts of the plants. In experiment I, three levels of water applied were studied: T1: non-stressed, maintained between 100 and 60% of the readily available soil water (RAW); T2: 60 and 30% of RAW; T3: \u3c 30% of RAW. Experiment II consisted of four water levels: T1: 100-80% RAW; T2: 80-60% RAW; T3: 60-40% of RAW; T4: \u3c 40% of RAW. In both experiments a complete randomized design was used. For sampling, plants were dug up from the pots and cut at the crown to separate the aerial part from the crown and roots. Formononetin concentration was evaluated by extracting with a methanol solution and relative quantifications based on HPLC–MS. Different water available levels were studied. Formononetin was much higher in the aerial part compared to roots. There were no significant effects of readily available soil water (RAW) over formononetin concentration

Was ist Männergesundheit? Eine Definition [What is Men's Health? A definition].

Zusammenfassung Ziel der Studie: Männergesundheit gerät immer stärker in den Fokus von Gesundheitsforschung, Epidemiologie, Gesundheitspflegeorganisation und Gesundheitspolitik. In den vergangenen 10–15 Jahren wurden von einigen Ländern und der EU Männergesundheitsberichte publiziert, in denen auf Probleme der Gesundheit beim Mann hingewiesen wurden. Ausgangspunkt für eine wissenschaftliche Untersuchung von Männergesundheit ist die Definition des Begriffs „Männergesundheit“. Eine Gruppe von deutschen Experten auf dem Gebiet von Männergesundheit hat sich dieser Aufgabe angenommen. Methodik: Eine Literaturrecherche in internationalen und nationalen Datenbanken erfolgte für die Jahre 1990–2014 nach ausgewählten MeSH Terms und nach „Experten für Männergesundheit“, nach „grauer Literatur“, in Gesundheitsberichten und Webseiten. Es folgte eine Expertenkonferenz zur Definitionsfindung mittels modifizierter Delphi Methode nach W. Zinn. Von der Expertengruppe wurden Mindestkriterien für eine Definition Männergesundheit erstellt und diskutiert, denen die neue Definition von Männergesundheit genügen muss. Daraus wurde in der dritten Runde schrittweise eine Definition erstellt. Ergebnisse: Die internationale Literaturrecherche ergab 7 Definitionen zu „Men’s Health“ in der englischsprachigen und 5 Definitionen in der deutschen inkl. in der „grauen“ Literatur. Aufgrund der von der Expertengruppe erarbeiteten 7 Mindestkriterien wurden 15 relevante Themengebiete gelistet, von denen durch Gewichtung 8 Themengebiete als relevant für eine neue Definition angesehen wurden. Im Abgleich mit den bisherigen Definitionen konnte keine diese 8 Kriterien erfüllen. Deshalb wurde im nächsten Arbeitsschritt von der Expertengruppe eine neue Definition Männergesundheit ausgearbeitet. Die Definition hat Bezug zum WHO-Begriff „Gesundheit“ und beinhaltet Dimensionen von Gesundheit und Krankheit, Risiko- und Schutzfaktoren, die spezielle Präventions- und Versorgungsangebote über alle Lebensphasen erfordern. Alle Teilnehmer der Expertengruppe stimmten der erarbeiteten Definition zu. Schlussfolgerung: Die Definition von Männergesundheit stellt eine Basis für weitere wissenschaftliche Arbeiten und die Praxis dar, um Männergesundheit in Deutschland und weiteren Ländern zu verbessern. ______________________________________________________________________________________ Summary Target of the study: Men’s Health is increasingly coming into focus of health research, epidemiology, health care organization, and health policy. Over the past 10–15 years have been published by some countries and the EU Men’s Health reports where problems of health noted in men. Starting point for a scientific study of men’s health is the definition of “Men’s Health”. A group of German experts in the field of men’s health has taken on this task. Methodology: A literature review in international and national databases was performed for the years 1990–2014 by selected MeSH terms and for “experts for men’s health”. Another research concerned “gray literature” in Germany, especially health reports and web pages. This was followed by a conference of experts to define “Men’s Health” using a modified Delphi method according to W. Zinn. From the expert group minimum criteria for a definition “Men’s Health” were created and discussed, which must comply with the new definition of men’s health. This definition was created in the third round of the Delphi method. Results: The international literature review yielded 7 definitions of “Men’s Health” in the English-speaking and 5 definitions in the German inkl. in the “gray” literature. Due to the developed by the Expert Group 7 minimum criteria 15 relevant topics were listed, of which by weighting 8 subject areas were considered relevant for a new definition. In comparison with the previous definitions none could fulfill these 8 criteria. Therefore, in the next step of the expert group a new definition “Men’s Health” was elaborated. The definition has reference to the WHO concept of “health” and includes dimensions of health and disease, risk and protective factors that require special prevention and care services for all phases of life. All participants in the expert group agreed on the definition developed. Conclusions: The definition of Men’s Health is a basis for further scientific work and practice to improve men’s health in Germany and other countries. Schlüsselwörter Männergesundheit - Gesundheitsressourcen - Lebensstil - Lebensqualität - Gesundheitsangebote für Männer Key words men’s health - health resources - lifestyle - quality of life - delivery of health services for me

Differential formononetin content in cultivars and experimental lines of red clover (Trifolium pratense L.) plants affect the feeding behaviour of Hylastinus obscurus (Coleoptera: Curculionidae)

Red clover (Trifolium pratense L.) is a perennial plant widely used as a forage resource for several animals. This plant is the exclusive host of Hylastinus obscurus (Marsham) which causes irreparable damages to the root system affecting their persistence. It has been reported that the presence of the isoflavonoid formononetin in roots of red clover could act as an antifeedant on H. obscurus. There are not studies related to the formononetin content in red clover roots to the antifeedant effect elicited by experimental lines and cultivar of red clover. Six red clover genotypes were investigated in both formononetin content and their respective antifeedant action. The results showed to Sabtoron High and Superqueli-INIA with both the highest formononetin content in red clover roots and antifeedant effect, allowing to suggest that this secondary metabolites could be used as a chemical factor for red clover plants. Moreover, a rapid methodology for searching red clover genotypes with high formononetin content is reported

Vascular co-option

Vascular co-option is an alternative mechanism to interact with blood vessels used by normal cells and hijacked by cancer cells. Functional experiments using in vivo models have demonstrated that co-option of pre-existing capillary networks is a critical step for the initiation of multiorgan metastases from different cancer types. Thus targeting this process pharmacologically is a very promising strategy to prevent metastases. Vascular co-option supports the viability of disseminated tumor cells, even when they remain dormant. Additionally, targeting vascular co-option could be a valuable strategy to challenge the emergence of resistance to more conventional therapies.S

Methodological considerations concerning the development of oral dental erosion indexes: literature survey, validity and reliability

Within the context of preventing non-communicable diseases, the World Health Report (2002) and the WHO Global Oral Health Program (2003) put forward a new strategy of disease prevention and health promotion. Greater emphasis is placed on developing global policies in oral health promotion and oral disease prevention. The Decayed, Missing, Filled Teeth (DMFT) index does not meet new challenges in the field of oral health. Dental erosion seems to be a growing problem, and in some countries, an increase in erosion of teeth is associated with an increase in the consumption of beverages containing acids. Therefore, within a revision of the WHO Oral Health Surveys Basic Methods, new oral disease patterns, e.g. dental erosion, have to be taken into account. Within the last 20 years, many studies on dental erosion have been carried out and published. There has been a rapid growth in the number of indexes quantifying dental erosion process in different age groups. However, these indexes are not comparable. This article discusses quality criteria which an index intended for assessing tooth erosion should possess

The neurogenic potential of astrocytes is regulated by inflammatory signals

Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these 'reactive' astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage-restricted astrocytes to either tumor necrosis factor alpha (TNF-α) (via nuclear factor-κB (NFκB)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-β1 and peroxisome proliferator-activated receptor gamma (PPARγ)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes