73 research outputs found

    β2-adrenergic agonists modulate TNF-α induced astrocytic inflammatory gene expression and brain inflammatory cell populations

    Get PDF
    Background: The NF-kappa B signaling pathway orchestrates many of the intricate aspects of neuroinflammation. Astrocytic beta(2)-adrenergic receptors have emerged as potential regulators in central nervous system inflammation and are potential targets for pharmacological modulation. The aim of this study was to elucidate the crosstalk between astrocytic beta(2)-adrenergic receptors and the TNF-alpha induced inflammatory gene program. Methods: Proinflammatory conditions were generated by the administration of TNF-alpha. Genes that are susceptible to astrocytic crosstalk between beta(2)-adrenergic receptors (stimulated by clenbuterol) and TNF-alpha were identified by qPCR-macroarray-based gene expression analysis in a human 1321 N1 astrocytoma cell line. Transcriptional patterns of the identified genes in vitro were validated by RT-PCR on the 1321 N1 cell line as well as on primary rat astrocytes. In vivo expression patterns were examined by intracerebroventricular administration of clenbuterol and/or TNF-alpha in rats. To examine the impact on the inflammatory cell content of the brain we performed extensive FACS analysis of rat brain immune cells after intracerebroventricular clenbuterol and/or TNF-alpha administration. Results: Parallel transcriptional patterns in vivo and in vitro confirmed the relevance of astrocytic beta(2)-adrenergic receptors as modulators of brain inflammatory responses. Importantly, we observed pronounced effects of beta(2)-adrenergic receptor agonists and TNF-alpha on IL-6, CXCL2, CXCL3, VCAM1, and ICAM1 expression, suggesting a role in inflammatory brain cell homeostasis. Extensive FACS-analysis of inflammatory cell content in the brain demonstrated that clenbuterol/TNF-alpha co-administration skewed the T cell population towards a double negative phenotype and induced a shift in the myeloid brain cell population towards a neutrophilic predominance. Conclusions: Our results show that astrocytic beta(2)-adrenergic receptors are potent regulators of astrocytic TNF-alpha-activated genes in vitro and in vivo, and ultimately modulate the molecular network involved in the homeostasis of inflammatory cells in the central nervous system. Astrocytic beta(2)-adrenergic receptors and their downstream signaling pathway may serve as potential targets to modulate neuroinflammatory responses

    Parallel functional and stoichiometric trait shifts in South American and African forest communities with elevation

    Get PDF
    The Amazon and Congo basins are the two largest continuous blocks of tropical forest with a central role for global biogeochemical cycles and ecology. However, both biomes differ in structure and species richness and composition. Understanding future directions of the response of both biomes to environmental change is paramount. We used one elevational gradient on both continents to investigate functional and stoichiometric trait shifts of tropical forest in South America and Africa. We measured community-weighted functional canopy traits and canopy and topsoil delta N-15 signatures. We found that the functional forest composition response along both transects was parallel, with a shift towards more nitrogen-conservative species at higher elevations. Moreover, canopy and topsoil delta N-15 signals decreased with increasing altitude, suggesting a more conservative N cycle at higher elevations. This cross-continental study provides empirical indications that both South American and African tropical forest show a parallel response with altitude, driven by nitrogen availability along the elevational gradients, which in turn induces a shift in the functional forest composition. More standardized research, and more research on other elevational gradients is needed to confirm our observations

    Multi-scale lidar measurements suggest miombo woodlands contain substantially more carbon than thought

    Get PDF
    Miombo woodlands are integral to livelihoods across southern Africa, biodiversity in the region, and the global carbon cycle, making accurate and precise monitoring of their state and change essential. Here, we assembled a terrestrial and airborne lidar dataset covering 50 kha of intact and degraded miombo woodlands, and generated aboveground biomass estimates with low uncertainty via direct 3D measurements of forest structure. We found 1.71 ± 0.09 TgC was stored in aboveground biomass across this landscape, between 1.5 and 2.2 times more than the 0.79–1.14 TgC estimated by conventional methods. This difference is in part owing to the systematic underestimation of large trees by allometry. If these results were extrapolated across Africa’s miombo woodlands, their carbon stock would potentially require an upward revision of approximately 3.7 PgC, implying we currently underestimate their carbon sequestration and emissions potential, and disincentivise their protection and restoration

    Breech presentation at term and associated obstetric risks factors-a nationwide population based cohort study

    Get PDF
    Purpose The aim of this study was to estimate whether breech presentation at term was associated with known individual obstetric risk factors for adverse fetal outcome. Methods This was a retrospective, nationwide Finnish population-based cohort study. Obstetric risks in all breech and vertex singleton deliveries at term were compared between the years 2005 and 2014. A multivariable logistic regression model was used to determine significant risk factors. Results The breech presentation rate at term for singleton pregnancies was 2.4%. The stillbirth rate in term breech presentation was significantly higher compared to cephalic presentation (0.2 vs 0.1%). The odds ratios (95% CIs) for fetal growth restriction, oligohydramnios, gestational diabetes, a history of cesarean section and congenital fetal abnormalities were 1.19 CI (1.07-1.32), 1.42 CI (1.27-1.57), 1.06 CI (1.00-1.13), 2.13 (1.98-2.29) and 2.01 CI (1.92-2.11). Conclusions The study showed that breech presentation at term on its own was significantly associated with antenatal stillbirth and a number of individual obstetric risk factors for adverse perinatal outcomes. The risk factors included oligohydramnios, fetal growth restriction, gestational diabetes, history of caesarean section and congenital anomalies.Peer reviewe

    Human-based fibrillar nanocomposite hydrogels as bioinstructive matrices to tune stem cell behavior

    Get PDF
    The extracellular matrix (ECM)-biomimetic fibrillar structure of platelet lysate (PL) gels along with its enriched milieu of biomolecules has drawn significant interest in regenerative medicine applications. However, PL-based gels have poor structural stability which severely limits its performance as a bioinstructive biomaterial. Here, rod-shaped cellulose nanocrystals (CNC) are used as a novel approach to modulate the physical and biochemical microenvironment of PL gels enabling their effective use as injectable human-based cell scaffolds with a level of biomimicry that is difficult to recreate with synthetic biomaterials. The incorporation of CNC (0 to 0.61 wt.%) into the PL fibrillar network during the coagulation cascade leads to decreased fiber branching, increased interfiber porosity (from 66 to 83%) and modulate fiber (from 1.4 ± 0.7 to 27 ± 12 kPa) and bulk hydrogel (from 18 ± 4 to 1256 ± 82 Pa) mechanical properties. As result of these physicochemical alterations, nanocomposite PL hydrogels resist to the typical extensive clot retraction (from 76 ± 1 to 24 ± 3 at Day 7) and show favored retention of PL bioactive molecules. The feedback of these cues on the fate of human adipose-derived stem cells is evaluated, showing how it can be explored to modulate the commitment of encapsulated stem cells toward different genetic phenotypes without the need for additional external biological stimuli. These fibrillar nanocomposite hydrogels allow therefore to explore the outstanding biological properties of human-based PL as an efficient engineered ECM which can be tailored to trigger specific regenerative pathways in minimal invasive strategies.The authors thank the Hospital da Prelada (Porto, Portugal) for providing adipose tissue samples. The authors acknowledge the financial support from project Recognize (UTAP-ICDT/CTM-BIO/0023/2014), project NORTE-01-0145FEDER-000021 supported by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No. 739572 – The Discoveries CTR EU, Forecast 668983, Marie Skłodowska-Curie grant agreement No. 706996 (PrinTendon) and CHEM2NATURE 692333; FCT/MCTES (Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia, e Ensino Superior) and the Fundo Social Europeu através do Programa Operacional do Capital Humano (FSE/POCH) in the framework of PhD grant PD/59/2013 – PD/BD/113807/2015 for BBM, Post-Doc grant SFRH/BPD/112459/2015 for R.D.info:eu-repo/semantics/publishedVersio

    Prix Louis Baes (9e période biennale, 1978-1979). Rapport du jury

    No full text
    Demol L., Biot Maurice Anthony, Jaumotte André Louis. Prix Louis Baes (9e période biennale, 1978-1979). Rapport du jury . In: Bulletin de la Classe des sciences, tome 66, 1980. p. 746

    Prix Louis Baes (9e période biennale, 1978-1979). Rapport du jury

    No full text
    Demol L., Biot Maurice Anthony, Jaumotte André Louis. Prix Louis Baes (9e période biennale, 1978-1979). Rapport du jury . In: Bulletin de la Classe des sciences, tome 66, 1980. p. 746
    • …
    corecore