Neuronal hypoxia in vitro: Investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells

Background The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. Methods A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array. Results tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% ± 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% ± 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. Conclusion Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes

Geographical and temporal trends in Late Quaternary fire histories of Fuego-Patagonia, South America

In Fuego-Patagonia. South America, the long-term interactions between climate and fire are still poorly understood and the importance of climate as a determinant of postglacial (after ca 17 ka BP) fire patterns is controversial. One means of addressing this issue is to investigate whether regional differences in fire histories are related to climatic gradients. For this purpose, we compile characteristic charcoal sequences from the literature and our own research along the southwest northeast precipitation gradient across the Andes. Postglacial fire histories along two transects in southern Patagonia and Tierra del Fuego show distinct geographical trends, reflecting changes in effective moisture. Throughout the Holocene, high fire activity has been associated with environments similar to the modern steppe-forest ecotone. Xeric woodlands and scrub-steppe probably combined a high density of human ignition sources with fire-conducive fuel characteristics. To separate the impact of Palco-Indians on fire Occurrence from the influence of climate is difficult, as human fire ignition was likely focused in the most fire-prone environments. However, independent of the type of ignition source (Paleo-Indians or lightning), fire-conducive climate conditions appear to have been a prerequisite for the spread of fires. (C) 2004 Elsevier Ltd. All rights reserved

Fuzzy model-based reconstruction of paleovegetation in Ethiopia

We introduce a new method to compute plant distribution in Ethiopia under paleoclimatic conditions using fuzzy logic. Using a published map of the potential vegetation for Ethiopia we decipher the boundary conditions for the main vegetation units shown, reflecting modern climatic conditions for temperature and precipitation in this region. Fuzzy logic using these climatic values on a GIS platform then derived the computational map of the potential vegetation. Comparing it with the original map shows a general correspondence of about 90%. By changing the underlying climate parameters, we then used this model for hypothetical paleoclimatic conditions to simulate the vegetational response on these changed climate settings. Finally, vegetational response maps for Ethiopia are presented for two scenarios: (i) a colder and drier condition (such as the Last Glacial Maximum) and (ii) a warmer and wetter condition (such as the last interglacial) than today

Auf der Spur der Menschen vor 80.000 Jahren

Was wissen wir über die ersten Wanderungsbewegungen unserer Vorfahren, die vor 80.000 bis 60.000 Jahren lebten? Ergebnisse aus Geographie, Archäologie und Ethnologie fließen in diese Graphic Novel ein. Basierend auf wissenschaftlichen Rekonstruktionen wird die fiktive Geschichte der jungen Aluru erzählt. Aluru begibt sich auf eine lange Reise – aus dem afrikanischen Rift Valley bis zur arabischen Halbinsel. Dabei durchwandert sie verschiedene Landschaften und Klimazonen, begegnet anderen Menschengruppen und muss sich immer wieder neu orientieren und behaupten. Begleitet wird die Comicgeschichte durch Sachkommentare; darin wird dargestellt, was wir über diese Periode der Altsteinzeit wissen, was wir vermuten – und was wir nicht wissen. So können sich alle Leser:innen ein eigenes Bild einer lang vergangenen Zeit machen

A high-resolution Early Holocene-late MIS 3 environmental rock- and palaeomagnetic record from Lake Sf. Ana, Carpathian Mts, Romania

Lacustrine sediments are excellent sources of palaeoenvironmental and palaeoclimatic information because they usually provide continuous and high-resolution records. In centraleastern Europe however lacustrine records that extend beyond the Holocene are rather sparse.Palaeomagnetic records from this region are also insufficiently explored, and usually associated with terrestrial deposits such as loess. In this context, the lacustrine record of Lake Sf. Ana, a volcanic crater lake in the East Carpathians, Romania, provides an important archive for reconstructing past paleomagnetic secular variation in the region from early Holocene to late Marine Isotope Stage (MIS) 3.</p

Potential and limits of combining studies of coarse- and fine-grained sediments for the coastal event history of a Caribbean carbonate environment

The coastal deposits of Bonaire, Leeward Antilles, are among the most studied archives for extreme-wave events (EWEs) in the Caribbean. Here we present more than 400 electron spin resonance (ESR) and radiocarbon data on coarse-clast deposits from Bonaire’s eastern and western coasts. The chronological data are compared to the occurrence and age of fine-grained extreme-wave deposits detected in lagoons and floodplains. Both approaches are aimed at the identification of EWEs, the differentiation between extraordinary storms and tsunamis, improving reconstructions of the coastal evolution, and establishing a geochronological framework for the events. Although the combination of different methods and archives contributes to a better understanding of the interplay of coastal and archive-related processes, insufficient separation, superimposition or burying of coarse-clast deposits and restricted dating accuracy limit the use of both fine-grained and coarse-clast geoarchives to unravel decadal- to centennial-scale events. At several locations, distinct landforms are attributed to different coastal flooding events interpreted to be of tsunamigenic origin. Coastal landforms on the western coast have significantly been influenced by (sub)-recent hurricanes, indicating that formation of the coarse-clast deposits on the eastern coast is likely to be related to past events of higher energy

Central IGF-I Receptors in the Brain are Instrumental to Neuroprotection by Systemically Injected IGF-I in a Rat Model for Ischemic Stroke

Aim: Insulin-like growth factor I (IGF-I) is a neuroprotective agent in animal models of ischemic stroke. The purpose of this study was to determine whether systemically injected IGF-I exerts its neuroprotective action by binding to IGF-I receptors in the brain after crossing the blood-brain barrier, or via peripheral effects. Methods: To differentiate the central effects of IGF-I from systemic effects, ischemic stroke was induced in conscious male Wistar Kyoto rats by the injection of endothelin-1 adjacent to the middle cerebral artery in the right hemisphere, while either the IGF-I receptor antagonist JB-1 or vehicle was introduced into the right lateral ventricle. Results: Intravenous injection of recombinant human (rh) IGF-I resulted in 50% reduction in infarct size, which was counteracted by the central administration of JB-1. Furthermore, rhIGF-I was detected in both the ischemic and nonischemic hemisphere. Conclusions: Systemically injected rhIGF-I passes the blood-brain barrier and protects neurons via IGF-I receptors in the brain in rats with an ischemic stroke

Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial

BACKGROUND AND PURPOSE: Granulocyte colony-stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose-escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients. METHODS: G-CSF (135 microg/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836; www.clinicaltrial.gov). Main inclusion criteria were /=15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging). RESULTS: G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1. CONCLUSIONS: G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927836