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The Sonic Hedgehog (SHH) pathway plays a central role in the developing mammalian CNS. In our study, we aimed to investigate the spatiotemporal SHH pathway expression pattern in human fetal brains. We analyzed 22 normal fetal brains for Shh, Patched, Smoothened, and Gli1-3 expression by immunohistochemistry. In the telencephalon, strongest expression of Shh, Smoothened, and Gli2 was found in the cortical plate (CP) and ventricular zone. Patched was strongly upregulated in the ventricular zone and Gli1 in the CP. In the cerebellum, SHH pathway members were strongly expressed in the external granular layer (EGL). SHH pathway members significantly decreased over time in the ventricular and subventricular zone and in the cerebellar EGL, while increasing levels were found in more superficial telencephalic layers. Our findings show that SHH pathway members are strongly expressed in areas important for proliferation and differentiation and indicate a temporal expression gradient in telencephalic and cerebellar layers probably due to decreased proliferation of progenitor cells and increased differentiation. Our data about the spatiotemporal expression of SHH pathway members in the developing human brain serves as a base for the understanding of both normal and pathological CNS development.
Das Hauptziel der vorliegenden Arbeit war es, die energieabhängigen Wirkungsquerschnitte von (γ,n)-Reaktionen für 169Tm, 170Yb, 176Yb und 130Te mittels der Photoaktivierungsmethode zu bestimmen.
Dazu wurden zunächst die Effizienzen der verwendeten Detektoren mithilfe von Simulationen korrigiert, da die verwendeten Targets eine ausgedehnte Geometrie aufweisen im Gegensatz zu den punktförmigen Eichquellen. Es hat sich herausgestellt, dass mit den Simulationen die Effizienzen der MCA-Detektoren energieabhängig korrigiert werden konnten, da die Simulationen die Form der gemessenen Effizienzen gut reproduzieren konnten. Bei den Effizienzen der LEPS-Detektoren hingegen konnte keine energieabhäangige Korrektur vorgenommen werden, da die LEPS-Detektoren aufgrund des geringen Abstandes zu den Detektoren hohe Summeneffekte zeigten. Im Rahmen dieser Arbeit konnten diese Summeneffekte jedoch nicht korrigiert bzw. berücksichtigt werden.
Numerous studies reported a strong link between working memory capacity (WMC) and fluid intelligence (Gf), although views differ in respect to how close these two constructs are related to each other. In the present study, we used a WMC task with five levels of task demands to assess the relationship between WMC and Gf by means of a new methodological approach referred to as fixed-links modeling. Fixed-links models belong to the family of confirmatory factor analysis (CFA) and are of particular interest for experimental, repeated-measures designs. With this technique, processes systematically varying across task conditions can be disentangled from processes unaffected by the experimental manipulation. Proceeding from the assumption that experimental manipulation in a WMC task leads to increasing demands on WMC, the processes systematically varying across task conditions can be assumed to be WMC-specific. Processes not varying across task conditions, on the other hand, are probably independent of WMC. Fixed-links models allow for representing these two kinds of processes by two independent latent variables. In contrast to traditional CFA where a common latent variable is derived from the different task conditions, fixed-links models facilitate a more precise or purified representation of the WMC-related processes of interest. By using fixed-links modeling to analyze data of 200 participants, we identified a non-experimental latent variable, representing processes that remained constant irrespective of the WMC task conditions, and an experimental latent variable which reflected processes that varied as a function of experimental manipulation. This latter variable represents the increasing demands on WMC and, hence, was considered a purified measure of WMC controlled for the constant processes. Fixed-links modeling showed that both the purified measure of WMC (β = .48) as well as the constant processes involved in the task (β = .45) were related to Gf. Taken together, these two latent variables explained the same portion of variance of Gf as a single latent variable obtained by traditional CFA (β = .65) indicating that traditional CFA causes an overestimation of the effective relationship between WMC and Gf. Thus, fixed-links modeling provides a feasible method for a more valid investigation of the functional relationship between specific constructs.
Background: Hypoxia is a key driver for infiltrative growth in experimental gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. We therefore investigated the influence of perioperative cerebral ischemia on patterns of progression in glioblastoma patients.
Methods: We retrospectively screened MRI scans of 245 patients with newly diagnosed glioblastoma undergoing resection for perioperative ischemia near the resection cavity. 46 showed relevant ischemia nearby the resection cavity. A control cohort without perioperative ischemia was generated by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment. Both cohorts were analyzed for patterns of progression by a blinded neuroradiologist.
Results: The percentage of diffuse or distant recurrences at first relapse was significantly higher in the cohort with perioperative ischemia (61.1%) compared to the control cohort (19.4%). The results of the control cohort matched well with historical data. The change in patterns of progression was not associated with a difference in survival.
Conclusions: This study reveals an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients.
This thesis presents microstructural investigations of rock salt from the central part of the Gorleben salt dome (Northern Germany). The main emphasis was to characterize the rock salt microfabrics, to identify operating deformation mechanisms in halite and anhydrite and to decipher the macro- and microstructural distribution of hydrocarbons, which have been encountered during the underground exploration of the salt dome. The microfabrics of the Knäuel- and the Streifensalz formation indicate that strain-induced grain boundary migration has been active during deformation of halite. Crystal plastic deformation of halite is further documented by lattice bending, subgrain formation and minor subgrain rotation. Evidence for pressure solution of halite has not been found, but cannot be excluded because of the small grain size, the lack of LPO and the low differential stress (1.1 - 1.3 MPa) as deduced from subgrain-size piezometry. Solution precipitation creep was proven for intercalated anhydrite layers and clusters, which have been deformed in the brittle-ductile regime. Brittle deformation of anhydrite in terms of boudinage and fracturing was counteracted by viscous creep of halite which caused a re-sealing of fractures and a reestablishing of the characteristic sealing capacity of rock salt. Hydrocarbons are mainly located along cross cut 1 West of the Gorleben exploration mine and are heterogeneously distributed in the rock salt. They are incorporated in the rock salt foliation in the form of streaks, dispersed clouds, clusters and isolated patches. On the micro-scale, hydrocarbons are trapped along grain boundaries of halite and/or anhydrite, in micro-capillary tubes of anhydrite and in pore space of the rare rock salt with elevated porosity (< 1.26 vol.-%). Such elevated porosities correlate with elevated hydrocarbon concentrations of several hundred ppm. The overall concentrations of hydrocarbons, however, are very low (< 0.05 wt.-%). Elevated porosity is depicted to be a remnant originating from an early stage of salt uplift when fluid and hydrocarbons have migrated and spread from the Staßfurt Karbonat (z2SK) into the superjacent Gorleben Hauptsalz. During halokinesis and the strong reworking of the salt body hydrocarbons have been redistributed and dismembered resulting in the isolated present-day occurrences. The distribution of hydrocarbons shows no relation to local variations in the rock salt fabric. The microstructures of hydrocarbon-bearing and hydrocarbon-free Gorleben rock salt are not distinguishable from each other. Likewise, the presence of hydrocarbons should not have influenced the mechanical behavior or the rock salt as indicated by the microfabrics studied and by geomechanical data. The pure amounts of hydrocarbons are too low for any detectable impact on the barrier properties of this part of rock salt. Although hydrocarbons have migrated into the Gorleben Hauptsalz during an early stage of salt uplift when the sealing capacity of rock salt was diminished, the major implication of their isolated distribution patterns is that the Gorleben rock salt was able to regain its sealing capacity during subsequent deformation and re-equilibration. Former migration pathways for fluid and hydrocarbons have been healed and do not exist anymore. The application of X-ray computed tomography (CT) allows the 3D visualization and quantification of anhydrite, pore space and fluid phases located along grain-boundaries or trapped as intracrystalline inclusions. The 3D reconstruction of anhydrite clusters and pore space for the same sample reveals different spatial distribution patterns. This fact implies that anhydrite is not responsible for such elevated pore space in the rock salt studied, which has been largely closed during the polyphase deformation history of the Gorleben salt dome. High-resolution nanoCT scans (≤ 1 μm voxel size) of single intra- and intercrystalline fluid inclusions in rock salt enable a characterization of gaseous, solid and liquid phases inside single fluid inclusions and give exact information on morphology and shape. The 3D reconstruction of grain boundary fluid inclusions allows the amount, volumes, surface areas or diameters of various types to be determined. Non-destructive X-ray CT imaging is presented as very useful tool to characterize the structural inventory of rock salt. This non-destructive technique offers new perspectives for microstructural studies and for a wide range of research in structural geology, in general.
Regulatory failures, which came to the fore after the financial crisis of 2007-2009, lead to the question of why some activities by financial institutions were not regulated prior to the crisis of 2007, even though regulators knew about certain dangers to financial stability? The repo-market, although centrally involved in the last crisis, still awaits stringent regulation. At the same time, the regulatory cycle seems to come to an end, boding ill for future crises which will be amplified by this market. In this situation, NGOs are needed to make regulators act upon their knowledge and to tighten their regulations.
Vor knapp zwei Wochen riss das Bangkok-Attentat am Erawan-Schrein 22 Menschen in den Tod und versetzte Thailands Hauptstadt in einen Schockzustand. Nach offiziellen Medien-Informationen vermuten Analysten ein Netzwerk hinter dem Anschlag. Diese Spekulationen konzentrieren sich besonders auf Regierungsgegner der sogenannten „Gelbhemden“ und „Rothemden“ oder muslimische Minderheiten...
Background: Detailed injury data are not available for international tournaments in field hockey. We investigated the epidemiology of field hockey injuries during major International Hockey Federation (Fédération Internationale de Hockey, FIH) tournaments in 2013.
Materials: and methods FIH injury reports were used for data collection. All major FIH tournaments for women (n=5) and men (n=11) in 2013 were included. The main focus of this study was to assess the pattern, time, site on the pitch, body site and mechanism of each of the injuries. We calculated the average number of injuries per match and the number of injuries per 1000 player match hours.
Results: The average number of injuries was 0.7 (95% CI 0.5 to 1.0) per match in women's tournaments and 1.2 (95% CI 0.8 to 1.7) per match in men's tournaments. The number of injuries per 1000 player match hours ranged from 23.4 to 44.2 (average 29.1; 95% CI 18.6 to 39.7) in women and 20.8 to 90.9 (average 48.3; 95% CI 30.9 to 65.8) in men. Most injuries occurred in the circle (n=25, 50%, in women, n=95, 51%, in men). The rate of injuries increased after the first quarter. Injuries to the head and face (n=20, 40%) were most common in women. The head/face (n=51, 27%) and the thigh/knee (n=52, 28%) were equally affected in men. The ball caused the most injuries, followed by the stick, collisions and tripping/falling. There were no deaths or injuries that required hospital treatment in the entire cohort.
Summary: Field hockey has a low incidence of acute injuries during competition.
BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has shown superior efficacy to etanercept with similar safety in moderate to severe plaque psoriasis (FIXTURE study).
OBJECTIVE: We sought to directly compare efficacy and safety of secukinumab versus ustekinumab.
METHODS: In this 52-week, double-blind study (NCT02074982), 676 subjects were randomized 1:1 to subcutaneous injection of secukinumab 300 mg or ustekinumab per label. Primary end point was 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at week 16.
RESULTS: Secukinumab (79.0%) was superior to ustekinumab (57.6%) as assessed by PASI 90 response at week 16 (P < .0001). The 100% improvement from baseline PASI score at week 16 was also significantly greater with secukinumab (44.3%) than ustekinumab (28.4%) (P < .0001). The 75% or more improvement from baseline PASI score at week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%) (P < .0001). Percentage of subjects with the Dermatology Life Quality Index score 0/1 (week 16) was significantly higher with secukinumab (71.9%) than ustekinumab (57.4%) (P < .0001). The safety profile of secukinumab was comparable with ustekinumab and consistent with pivotal phase III secukinumab studies.
LIMITATIONS: The study was not placebo-controlled and of short-term duration.
CONCLUSIONS: Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and improving health-related quality of life with a comparable safety profile over 16 weeks.
Hematopoietic stem cells (HSCs) have the unique abilities of life-long self-renewal and multi-lineage differentiation. They are routinely used in BM or stem cell transplantations to reconstitute the blood system of patients suffering from malignant or monogenic blood disorders. For an adequate production of each blood cell lineage in homeostasis and under stress conditions, the fate choice of HSCs to either self-renew or to differentiate must be strictly controlled. The incomplete understanding of the molecular mechanisms that control this balance makes it still impossible to maintain or expand undifferentiated HSCs in culture for advanced regenerative medical purposes.
The aim of this thesis was the identification and molecular characterisation of mechanisms that control the decision of HSCs to self-renew or to differentiate, and how they are connected to extrinsic cytokine signaling control. Prior to this thesis, a screening for genes upregulated under self-renewal promoting thrombopoietin (TPO) signaling via the transcription factors STAT5A/B in HSCs was conducted, and Growth arrest and DNA damage inducible 45 gamma (Gadd45g) was one of the regulated genes. GADD45G was described as stress sensor, DNA-damage response and tumor suppressor gene, that is epigenetically silenced in many solid tumors and leukemia. Furthermore, Gadd45g is upregulated in aged HSCs with impaired multi-lineage reconstitution abilities, and it is induced by differentiation promoting cytokines in GM-committed cells. However, the function of GADD45G in LT-HSCs was unknown. All these points warrant further investigation to unravel the function of GADD45G on early cell fate decisions of HSCs in hematopoiesis.
The expression of Gadd45g was stimulated by hematopoietic cytokines TPO, IL3 and IL6 both in HSCs and MPPs, making GADD45G an interesting target to focus on. To simulate the cytokine-induced expression GADD45G was lentivirally transduced in HSCs. Surprisingly, GADD45G did not induce cell cycle arrest or cell death in hematopoietic cells neither in vitro nor in vivo, as reported in many cell lines. Instead GADD45G revealed an enhanced and markedly accelerated differentiation of HSCs into mainly myelomonocytic cells, similar as observed for IL3 and IL6 containing cultures. Also in vivo, GADD45G rapidly initiates the differentiation program in HSCs at the expense of self-renewal and long-term engraftment, as shown by serial HSC transplantation experiments. Along the same line, HSCs from Gadd45g-knock out mice exhibited an increased self-renewal. In vitro, Gadd45g-/- progenitors showed higher and prolonged colony formation potential and slower expansion after cytokine stimulation. The loss of Gadd45g increased HSC self-renewal and improved repopulation in secondary recipients, determined by serial competitive transplantations. Taken together, GADD45G could be identified as molecular link between differentiation-promoting cytokine signaling and rapid differentiation induction in murine LT-HSCs.
As presented in this thesis the differentiation induction of GADD45G was mediated by the activation of the cascade of MAP3K4 – MKK6 –p38 MAPK. Small molecule inhibition of p38, but not JNK, blocked the GADD45G-induced differentiation. GADD45G binds to MAP3K4 and releases its auto-inhibitory loop by a change in confirmation, initiating this cascade. Phosphoflow cytometry demonstrated the activation of p38 and a downstream kinase MK2 by GADD45G expression in MPPs. Furthermore, the expression of constitutive active MAP3K4 and MKK6 were able to phenocopy GADD45G-induced differentiation, which could be blocked by p38 inhibition.
The other two family members GADD45A and B also induced accelerated differentiation in LT-HSCs. Interestingly, only GADD45G suppressed the differentiation into megakaryocyte and erythrocyte (Mek/E) lineage cells suggesting a role of GADD45G in lineage choice. Long-term time-lapse microscopy-based cell tracking of single LT-HSCs and their progeny revealed that, once GADD45G is expressed, the development of LT-HSCs into granulocyte-macrophage-committed progeny occurred within 36 hours, and uncovered a selective lineage choice with a severe reduction in Mek/E cells. Furthermore, no megakaryocytic-erythroid progenitors (MEPs) could develop from HSPCs in BM 2 weeks after transplantation suggesting a very early selection against Mek/E cell fates. In line with these findings, GADD45G-transduced MEPs could not expand or form colonies in vitro, demonstrating that the differentiation program induced by GADD45G is not compatible with Mek/E lineage fate. Gene expression profiling of HSCs indicated that GADD45G promotes myelomonocytic differentiation programs over programs for self-renewal or megakaryo-/ erythropoiesis. The here identified differentiation induction potential of GADD45G is so strong that the expression of GADD45G in primary acute myeloid leukemia (AML) cells inhibited their expansion accompanied by enhanced differentiation and increased apoptosis.
The here presented work shows that IL3 and IL6 induce a differentiation program in HSCs via GADD45G and p38 closing the link of extrinsic cytokine signaling and differentiation induction. Since the loss of Gadd45g increased the self-renewal and slowed HSC differentiation, this may be utilized, i.e. by p38 inhibition, to ex vivo maintain and expand HSCs by preventing cytokine-induced differentiation. Furthermore, Re-expression of GADD45G may overcome the differentiation block in leukemia to eliminate these cells by driving them into terminal differentiation and apoptosis.
Traditional chinese medicine and herbal hepatotoxicity: a tabular compilation of reported cases
(2015)
Traditional Chinese Medicine (TCM) with its focus on herbal use became popular worldwide. Treatment was perceived as safe, with neglect of rare adverse reactions including liver injury. To compile worldwide cases of liver injury by herbal TCM, we undertook a selective literature search in the PubMed database and searched for the items Traditional Chinese Medicine, TCM, Traditional Asian Medicine, and Traditional Oriental Medicine, also combined with the terms herbal hepatotoxicity or herb induced liver injury. The search focused primarily on English-language case reports, case series, and clinical reviews. We identified reported hepatotoxicity cases in 77 relevant publications with 57 different herbs and herbal mixtures of TCM, which were further analyzed for causality by the Council for International Organizations of Medical Sciences (CIOMS) scale, positive reexposure test results, or both. Causality was established for 28/57 different herbs or herbal mixtures, Bai Xian Pi, Bo He, Ci Wu Jia, Chuan Lian Zi, Da Huang, Gan Cao, Ge Gen, Ho Shou Wu, Huang Qin, Hwang Geun Cho, Ji Gu Cao, Ji Xue Cao, Jin Bu Huan, Jue Ming Zi, Jiguja, Kudzu, Ling Yang Qing Fei Keli, Lu Cha, Rhen Shen, Ma Huang, Shou Wu Pian, Shan Chi, Shen Min, Syo Saiko To, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, and Zhen Chu Cao. In conclusion, this compilation of liver injury cases establishes causality for 28/57 different TCM herbs and herbal mixtures, aiding diagnosis for physicians who care for patients with liver disease possibly related to herbal TCM.
Hepatology highlights
(2015)
Relacionar a temática referente a Teoria do Reconhecimento de Axel Honnet e o direito humano ao trabalho, como direito humano com pretensão de validade universal, sob a perspectiva da Declaração dos Direitos e Princípios Fundamentais no Trabalho da OIT, com fins de fixar parâmetros de reconhecimento e de (re)inserção social da categoria de trabalhadores toxicodependentes é o principal objetivo do presente artigo. Para tanto, analisaremos o marco teórico em que a persecução da dignidade do homem pelo trabalho é o objetivo do Estado para que a seguir possamos tratar da dignidade do homem como direito cuja pretensão de validade é universal, com base da teoria do reconhecimento de Axel Honneth. Isto posto, podemos analisar a possível dignificação do homem pelo trabalho e no trabalho, em um contexto global a partir dos efeitos do reconhecimento de novos direitos, especialmente no que tange à categoria de trabalhadores que ocupam a parcela social de químico-dependentes, cuja participação no processo social está impedida, gerando uma categoria de trabalhadores socialmente excluídos, o que se pretende ultrapassar.
Am GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, wird für die Erweiterung der Forschungsmöglichkeiten am Bau des FAIR Projektes gearbeitet. Hierfür wird unter anderem ein Ringbeschleuniger gebaut (SIS100), der mit 100Tm den bestehenden Ring (SIS18) in magnetischer Steifigkeit ergänzen wird. Um SIS100 an SIS18 anzubinden, wird eine Transferstrecke benötigt, welche den Transfer von Ionen zwischen den Ringen übernimmt. In solchen Transferstrecken werden Quadrupollinsen mit hohen Gradienten benötigt. Ebenso werden für die finale Fokussierung von hochintensiven Strahlpulsen aus Synchrotronen auf Targets Linsen mit hohen Feldgradienten benötigt. Allerdings sind die Pulse nur sehr kurz und das Tastverhältnis bei Synchrotronen sehr klein. Daher sollte ein gepulster Fokussiermagnet entwickelt werden, der den hohen Gradientenanforderungen gerecht wird und sowohl platz- als auch energiesparend ist. Die vorliegende Arbeit befasst sich mit der Auslegung des elektrischen Schaltkreises, der Simulation des Magnetfeldes und der konstruktiven Umsetzung eines solchen gepulsten Quadrupols. Der elektrische Schaltkreis ist so ausgelegt, dass eine hohe Repetitionsrate zur Fokussierung für Teilchenpakete möglich ist. Die Linse wurde aus einer Luftspule ohne Eisenjoch aufgebaut. Die cos(2θ)-Verteilung des Stroms durch die Leiter wurde durch ein Design gesichert, welches den Skin-Effekt berücksichtigt und entsprechend ausgelegte Litzenkabel verwendet. Um die Magnetfeldverteilung des Fokussiermagneten zu untersuchen, wurden statische und transiente Simulationen mit dem Programm CST Mircowave Studio Suite vorgenommen. Zentraler Punkt bei der Neuentwicklung waren die Luftspulen. Um einen linearen Magnetfeldanstieg von der Strahlachse zum Aperturrand zu gewährleisten, muss die Stromverteilung in der Leiterspule so homogen wie möglich sein. Um bei Pulslängen von 170 µsec den Skineffekt zu berücksichtigen, wurde die Leiterspule aus HF-Litzen von je mehreren hundert Einzelleitern zusammengestellt, die jeweils gegeneinander isoliert und in Bündeln miteinander verdrillt sind. Außerdem wurde die Linse mit einer lamellierten Schirmung versehen, um das Magnetfeld effektiv nutzen zu können. Ziel der Auslegung war es, zusammen mit einem zweiten Quadrupol im Duplett einen Strahl mit einer magnetischen Steifigkeit von 11 Tm und einer Bunchlänge von 2µsec auf einen Punkt von 0,5 mm Radius zu fokussieren. Bei dem hierfür angestrebten Gradienten von 76 T/m wird eine maximale Stromamplitude von 400 kA benötigt. Im Rahmen dieser Arbeit wurde die Linse ausgelegt, konstruiert und gebaut. Die Funktionalität wurde untersucht und die Feldqualität wurde vermessen und zeigten die erwarteten Parameter. Bei 26 kA Messstrom wurden im Zentrum des Magneten ein maximaler Gradient von 4,5 T/m und Feldwerte von 0,11 T ermittelt. Somit liegt die Abweichung des gemessenen Gradienten bei ca. 5 %. Die durchgängige Umsetzung der homogenen Verteilung der Leiterbündel in der Luftspule und eine vollständige Kompensation des Skineffekts konnten nicht nachgewiesen werden. Jedoch konnte der Einfluss der Kabelzuleitung des Quadrupols auf den Magnetfeldverlauf in den Simulationen und Messungen nachgewiesen werden. Weiterhin wurde für den energieeffizienten Einsatz im Transferkanal zwischen SIS18 und SIS100 ein Energierückgewinnungsschaltkreis entwickelt, der eine Ersparnis von 84 % der Betriebsleistung ermöglicht.
We examine how U.S. monetary policy affects the international activities of U.S. Banks. We access a rarely studied US bank‐level dataset to assess at a quarterly frequency how changes in the U.S. Federal funds rate (before the crisis) and quantitative easing (after the onset of the crisis) affects changes in cross‐border claims by U.S. banks across countries, maturities and sectors, and also affects changes in claims by their foreign affiliates. We find robust evidence consistent with the existence of a potent global bank lending channel. In response to changes in U.S. monetary conditions, U.S. banks strongly adjust their cross‐border claims in both the pre and post‐crisis period. However, we also find that U.S. bank affiliate claims respond mainly to host country monetary conditions.
Diese Arbeit stellt eine Annäherung an den umfangreichen Themenkomplex "Kind, Kunst und Kompensation" dar. In Auseinandersetzung mit unterschiedlichsten Berührungspunkten wird aufgezeigt, warum gestalterisch-schöpferische Betätigung förderlich und erforderlich für die Entwicklung ist, insbesondere im Kindesalter. Im Fokus der Betrachtung stehen zum einen grundlegende Wirkungsweisen, die diesen Prozessen innewohnen und zum anderen der sozioökonomische Wandel, welcher gerade jene Wirkungsweisen herausfordert und teilweise ebenso notwendig macht. Umhüllt wird dieser Bereich vom zentralen Themenkomplex der Handlungsverarmung, Vereinseitigung und Vielfalts-Debatte, welcher im Grunde nicht nur Heranwachsende, sondern letztlich jeden Menschen der westlichen Welt betrifft.
The fossil record is widely informative about evolution, but fossils are not systematically used to study the evolution of stem-cell-driven renewal. Here, we examined evolution of the continuous growth (hypselodonty) of rodent molar teeth, which is fuelled by the presence of dental stem cells. We studied occurrences of 3,500 North American rodent fossils, ranging from 50 million years ago (mya) to 2 mya. We examined changes in molar height to determine whether evolution of hypselodonty shows distinct patterns in the fossil record, and we found that hypselodont taxa emerged through intermediate forms of increasing crown height. Next, we designed a Markov simulation model, which replicated molar height increases throughout the Cenozoic and, moreover, evolution of hypselodonty. Thus, by extension, the retention of the adult stem cell niche appears to be a predictable quantitative rather than a stochastic qualitative process. Our analyses predict that hypselodonty will eventually become the dominant phenotype.
Microtubules execute diverse mitotic events that are spatially and temporally separated; the underlying regulation is poorly understood. By combining drug treatments, large-scale immunoprecipitation and mass spectrometry, we report the first comprehensive map of mitotic phase-specific protein interactions of the microtubule-end binding protein, EB1. EB1 interacts with some, but not all, of its partners throughout mitosis. We show that the interaction of EB1 with Astrin-SKAP complex, a key regulator of chromosome segregation, is enhanced during prometaphase, compared to anaphase. We find that EB1 and EB3, another EB family member, can interact directly with SKAP, in an SXIP-motif dependent manner. Using an SXIP defective mutant that cannot interact with EB, we uncover two distinct pools of SKAP at spindle microtubules and kinetochores. We demonstrate the importance of SKAP's SXIP-motif in controlling microtubule growth rates and anaphase onset, without grossly disrupting spindle function. Thus, we provide the first comprehensive map of temporal changes in EB1 interactors during mitosis and highlight the importance of EB protein interactions in ensuring normal mitosis.