Longitudinal data on telomere length in leukocytes from newborn baboons support a marked drop in stem cell turnover around 1 year of age

Stem cells of various tissues are typically defined as multipotent cells with 'self-renewal' properties. Despite the increasing interest in stem cells, surprisingly little is known about the number of times stem cells can or do divide over a lifetime. Based on telomere-length measurements of hematopoietic cells, we previously proposed that the self-renewal capacity of hematopoietic stem cells is limited by progressive telomere attrition and that such cells divide very rapidly during the first year of life. Recent studies of patients with aplastic anemia resulting from inherited mutations in telomerase genes support the notion that the replicative potential of hematopoietic stem cells is directly related to telomere length, which is indirectly related to telomerase levels. To revisit conclusions about stem cell turnover based on cross-sectional studies of telomere length, we performed a longitudinal study of telomere length in leukocytes from newborn baboons. All four individual animals studied showed a rapid decline in telomere length (approximately 2-3 kb) in granulocytes and lymphocytes in the first year after birth. After 50-70 weeks the telomere length appeared to stabilize in all cell types. These observations suggest that hematopoietic stem cells, after an initial phase of rapid expansion, switch at around 1 year of age to a different functional mode characterized by a markedly decreased turnover rate.

Tenascins in stem cell niches.

Tenascins are extracellular matrix proteins with distinct spatial and temporal expression during development, tissue homeostasis and disease. Based on their expression patterns and knockout phenotypes an important role of tenascins in tissue formation, cell adhesion modulation, regulation of proliferation and differentiation has been demonstrated. All of these features are of importance in stem cell niches where a precise regulation of growth versus differentiation has to be guaranteed. In this review we summarize the expression and possible functions of tenascins in neural, epithelial and osteogenic stem cell niches during normal development and organ turnover, in the hematopoietic and pro-inflammatory niche as well as in the metastatic niche during cancer progression.

Functional Characterization and Comparison of Intercellular Communication in Stem Cell-Derived Cardiomyocytes

One novel treatment strategy for the diseased heart focuses on the use of pluripotent stem cell-derived cardiomyocytes (SC-CMs) to overcome the heart's innate deficiency for self-repair. However, targeted application of SC-CMs requires in-depth characterization of their true cardiogenic potential in terms of excitability and intercellular coupling at cellular level and in multicellular preparations. In this study, we elucidated the electrical characteristics of single SC-CMs and intercellular coupling quality of cell pairs, and concomitantly compared them with well-characterized murine native neonatal and immortalized HL-1 cardiomyocytes. Firstly, we investigated the electrical properties and Ca2+ signaling mechanisms specific to cardiac contraction in single SC-CMs. Despite heterogeneity of the new cardiac cell population, their electrophysiological activity and Ca2+ handling were similar to native cells. Secondly, we investigated the capability of paired SC-CMs to form an adequate subunit of a functional syncytium and analyzed gap junctions and signal transmission by dye transfer in cell pairs. We discovered significantly diminished coupling in SC-CMs compared with native cells, which could not be enhanced by a coculture approach combining SC-CMs and primary CMs. Moreover, quantitative and structural analysis of gap junctions presented significantly reduced connexin expression levels compared with native CMs. Strong dependence of intercellular coupling on gap junction density was further confirmed by computational simulations. These novel findings demonstrate that despite the cardiogenic electrophysiological profile, SC-CMs present significant limitations in intercellular communication. Inadequate coupling may severely impair functional integration and signal transmission, which needs to be carefully considered for the prospective use of SC-CMs in cardiac repair.

Last stop expulsion - The minority question and forced migration in East-Central Europe: 1918-49

This article deals with the European minorities in the period between the two world wars and with their final expulsion from nation-states at the end of World War II. First, the tensions which arose between the organised minorities and the successor states of the Habsburg Monarchy are accounted for primarily by the argument that the various minorities located within the successor states had already undergone a comprehensive processes of nationalisation within the Habsburg Empire. Therefore they were able to resist assimilation by the political elites of the new titular nations (Czechs, Poles, Rumanians, Serbs). A second topic is that of the use made of the minorities issue by Adolf Hitler to help achieve his expansionist aims. The minorities issue was central to the international destabilisation of interwar Europe. Finally, the mass expulsion of minorities (above all, Germans) after the end of the war is explained by strategic considerations on the part of the Allied powers as well as involving the nation-state regimes. It is argued, against a commonly held view, that German atrocities during the period of occupation had little to do with the decision to expel most ethnic Germans from their territories of settlement in Poland, Czechoslovakia and Yugoslavia. The article shows that it is necessary to treat national minorities in the first half of the twentieth century as a single phenomenon which shares similar features across the various nation-states of East-Central Europe.

Kriegsverbrechen – Verbrechen gegen die Menschlichkeit – Völkermord? Zeitgenössische Völkerrechtler und die Deportation der christlichen Minderheiten in Anatolien während des Ersten Weltkrieges

This presentation concentrates on the role that the deportation of Christian minorities in Anatolia during the First World War played in the context of the history of law. Terminologies and the use of legal notions by contemporaries will be a special focus, because this is still helpful in the context of present-day discussions. Therefore a contextualisation as precise as possible is important, when the topic of deportation and genocide is addressed. At the same time it is important not to confuse historical and legal appraisals. In this presentation the general discussion as to the prospects and potential of a judicial punishment of violations of international legal norms before as well as during the First World War will therefore be included as much as the attitude of jurists in regard to the position of the Ottoman Empire within the international community of law abiding states. Finally this presentation will also focus on discussions at the end of the war around the trials in Istanbul and the purpose of the Paris Peace Conference. In this context and following ideas of Mahmood Mamdani the discourse on law can be shown to have served not only as a way of giving victims a voice, but also as a language of power already at the beginning of the 20th century.

Improving chondrogenesis: potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering

Articular cartilage injuries and degeneration affect a large proportion of the population in developed countries world wide. Stem cells can be differentiated into chondrocytes by adding transforming growth factor-beta1 and dexamethasone to a pellet culture, which are unfeasible for tissue engineering purposes. We attempted to achieve stable chondrogenesis without any requirement for exogenous growth factors. Human mesenchymal stem cells were transduced with an adenoviral vector containing the SRY-related HMG-box gene 9 (SOX9), and were cultured in a three-dimensional (3D) hydrogel scaffold composite. As an additional treatment, mechanical stimulation was applied in a custom-made bioreactor. SOX9 increased the expression level of its known target genes, as well as its cofactors: the long form of SOX5 and SOX6. However, it was unable to increase the synthesis of sulfated glycosaminoglycans (GAGs). Mechanical stimulation slightly enhanced collagen type X and increased lubricin expression. The combination of SOX9 and mechanical load boosted GAG synthesis as shown by (35)S incorporation. GAG production rate corresponded well with the amount of (endogenous) transforming growth factor-beta1. Finally, cartilage oligomeric matrix protein expression was increased by both treatments. These findings provide insight into the mechanotransduction of mesenchymal stem cells and demonstrate the potential of a transcription factor in stem cell therapy.

Bacterial meningitis impairs hippocampal neurogenesis

Bacterial meningitis causes persisting neurofunctional sequelae. Theoccurrence of apoptotic cell death in the hippocampal subgranular zone of the dentate gyrus characterizes the disease in patients and relates to deficits in learning and memory in corresponding experimental models. Here, we investigated why neurogenesis fails to regenerate the damage in the hippocampus associated with the persistence of neurofunctional deficits. In an infant rat model of bacterial meningitis, the capacity of hippocampal-derived cells to multiply and form neurospheres was significantly impaired comparedto that in uninfected littermates. In an in vitro model of differentiating hippocampal cells, challenges characteristic of bacterial meningitis (i.e. bacterial components, tumor necrosis factor [20 ng/mL], or growth factor deprivation) caused significantly more apoptosis in stem/progenitor cells and immature neurons than in mature neurons. These results demonstrate that bacterial meningitis injures hippocampal stem and progenitor cells, a finding that may explain the persistence of neurofunctional deficits after bacterial meningitis.

General Protocol for the Culture of Cells on Plasma-Coated Electrospun Scaffolds

As opposed to culture on standard tissue-treated plastic, cell culture on three-dimensional scaffolds impedes additional challenges with respect to substrate preparation, cell seeding, culture maintenance, and analysis. We herewith present a general route for the culture of primary cells, differentiated cells, or stem cells on plasma-coated, electrospun scaffolds. We describe a method to prepare and fix the scaffolds in culture wells and discuss a convenient method for cell seeding and subsequent analysis by scanning electron microscopy or immunohistology.

Gluema korupensis (Sapotaceae), a new tree species from Korup National Park, Cameroon

Gluema korupensis Burgt (Sapotaceae), a new species from the southern part of Korup National Park in Cameroon, is described and illustrated. In total 176 trees 2 25 cm in stem diam. were found. The tree from which the holotype was collected was 42 m high and 125 cm in diam.; the largest tree was 238 cm in diam. The seeds are dispersed ballistically and sometimes by water

Climatic drivers of hourly to yearly tree radius variations along a 6°C natural warming gradient

Climate affects the timing, rate and dynamics of tree growth, over time scales ranging from seconds to centuries. Monitoring how a tree's stem radius varies over these time scales can provide insight into intra-annual stem dynamics and improve our understanding of climate impacts on tree physiology and growth processes. Here, we quantify the response of radial conifer stem size to environmental fluctuations via a novel assessment of tree circadian cycles. We analyze four years of sub-hourly data collected from 56 larch and spruce trees growing along a natural temperature gradient of ∼6 °C in the central Swiss Alps. During the growing season, tree stem diameters were greatest at mid-morning and smallest in the late evening, reflecting the daily cycle of water uptake and loss. Along the gradient, amplitudes calculated from the stem radius cycle were ∼50% smaller at the upper site (∼2200 m a.s.l.) relative to the lower site (∼800 m a.s.l.). We show changes in precipitation, temperature and cloud cover have a substantial effect on typical growing season diurnal cycles; amplitudes were nine times smaller on rainy days (>10 mm), and daily amplitudes are approximately 40% larger when the mean daily temperature is 15–20 °C than when it is 5–10 °C. We find that over the growing season in the sub-alpine forests, spruce show greater daily stem water movement than larch. However, under projected future warming, larch could experience up to 50% greater stem water use, which may severely affect future growth on already dry sites. Our data further indicate that because of the confounding influences of radial growth and short-term water dynamics on stem size, conventional methodology probably overstates the effect of water-linked meteorological variables (i.e. precipitation and relative humidity) on intra-annual tree growth. We suggest future studies use intra-seasonal measurements of cell development and consider whether climatic factors produce reversible changes in stem diameter. These study design elements may help researchers more accurately quantify and attribute changes in forest productivity in response to future warming.

Modeling tree water deficit from microclimate: an approach to quantifying drought stress

Tree water deficit estimated by measuring water-related changes in stem radius (DeltaW) was compared with tree water deficit estimated from the output of a simple, physiologically reasonable model (DeltaW(E)), with soil water potential (Psi(soil)) and atmospheric vapor pressure deficit (VPD) as inputs. Values of DeltaW were determined by monitoring stem radius changes with dendrometers and detrending the results for growth, We followed changes in DeltaW and DeltaW(E) in Pinus sylvestris L. and Quercus pubescens Willd. over 2 years at a dry site (2001-2002; Salgesch, Wallis) and in Picea abies (L.) Karst. for 1 year at a wet site (1998; Davos, Graubuenden) in the Swiss Alps. The seasonal courses of DeltaW in deciduous species and in conifers at the same site were similar and could be largely explained by variation in DeltaW(E). This finding strongly suggests that DeltaW, despite the known species-specific differences in stomatal response to microclimate, is mainly explained by a combination of atmospheric and soil conditions. Consequently, we concluded that trees are unable to maintain any particular DeltaW. Either Psi(soil) or VPD alone provided poorer estimates of AWthan a model incorporating both factors. As a first approximation of DeltaW(E), Psi(soil) can be weighted so that the negative mean Psi(soil) reaches 65 to 75% of the positive mean daytime VPD over a season (Q. pubescens: similar to65%, P abies: similar to70%, P sylvestris: similar to75%). The differences in DeltaW among species can be partially explained by a different weighting of Psi(soil) against VPD. The DeltaW of P. sylvestris was more dependent on Psi(soil) than that of Q. pubescens, but less than that of P. abies, and was less dependent on VPD than that of P. abies and Q. pubescens. The model worked well for P. abies at the wet site and for Q. pubescens and P. sylvestris at the dry site, and may be useful for estimating water deficit in other tree species.

Life-long growth of Quercus ilex L. at natural CO2 springs acclimates sulphur, nitrogen and carbohydrate metabolism of the progeny to elevated pCO2

The aim of the present study was to analyse whether offspring of mature Quercus ilex trees grown under life-long elevated pCO2 show alterations in the physiological response to elevated pCO2 in comparison with those originating from mature trees grown at current ambient pCO2. To investigate changes in C- (for changes in photosynthesis, biomass and lignin see Polle, McKee & Blaschke Plant, Cell and Environment 24, 1075–1083, 2001), N-, and S-metabolism soluble sugar, soluble non-proteinogenic nitrogen compounds (TSNN), nitrate reductase (NR), thiols, adenosine 5′-phosphosulphate (APS) reductase, and anions were analysed. For this purpose Q. ilex seedlings were grown from acorns of mother tree stands at a natural spring site (elevated pCO2) and a control site (ambient pCO2) of the Laiatico spring, Central Italy. Short-term elevated pCO2 exposure of the offspring of control oaks lead to higher sugar contents in stem tissues, to a reduced TSNN content in leaves, and basipetal stem tissues, to diminished thiol contents in all tissues analysed, and to reduced APS reductase activity in both, leaves and roots. Most of the components of C-, N- and S-metabolism including APS reductase activity which were reduced due to short-term elevated pCO2 exposure were recovered by life-long growth under elevated pCO2 in the offspring of spring oaks. Still TSNN contents in phloem exudates increased, nitrate contents in lateral roots and glutathione in leaves and phloem exudates remained reduced in these plants. The present results demonstrated that metabolic adaptations of Q. ilex mother trees to elevated pCO2 can be passed to the next generation. Short- and long-term effects on source-to-sink relation and physiological and genetic acclimation to elevated pCO2 are discussed.