817 research outputs found

    IDEAL Symposium on the East African Lakes

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94975/1/eost9699.pd

    Improved modeling of sediment oxygen kinetics and fluxes in lakes and reservoirs

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    To understand water quality degradation during hypoxia, we need to understand sediment oxygen fluxes, the main oxygen sink in shallow hypolimnia. Kinetic models, which integrate diffusion and consumption of dissolved oxygen (DO) in sediments, usually assume a downward flux of DO from the sediment−water interface (SWI) with a zero-flux condition at the lower boundary of the oxic sediment layer. In this paper, we separately account for the oxidation of an upward flux of reduced compounds by introducing a negative flux of DO as a lower boundary condition. Using in situ measurements in two lakes, kinetic models were fit to DO microprofiles using zero-order and first-order kinetics with both zero and non-zero lower boundary conditions. Based on visual inspection and goodness-of-fit criteria, the negative-flux lower boundary condition, −0.25 g O2 m−2 d−1, was found to more accurately describe DO consumption kinetics. Fitted zero-order rate constants ranged from 50 to 510 mg L−1 d−1, and first-order rate constants ranged from 60 to 400 d−1, which agree well with prior laboratory studies. DO fluxes at the SWI calculated from the simulated profiles with the negative-flux lower boundary condition also showed better agreement with the observed DO fluxes than the simulated profiles with the zero-flux lower boundary condition

    The muscarinic receptor antagonist propiverine exhibits α1-adrenoceptor antagonism in human prostate and porcine trigonum

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    Combination therapy of male lower urinary tract symptoms with α(1)-adrenoceptor and muscarinic receptor antagonists attracts increasing interest. Propiverine is a muscarinic receptor antagonist possessing additional properties, i.e., block of L-type Ca(2+) channels. Here, we have investigated whether propiverine and its metabolites can additionally antagonize α(1)-adrenoceptors. Human prostate and porcine trigone muscle strips were used to explore inhibition of α(1)-adrenoceptor-mediated contractile responses. Chinese hamster ovary (CHO) cells expressing cloned human α(1)-adrenoceptors were used to determine direct interactions with the receptor in radioligand binding and intracellular Ca(2+) elevation assays. Propiverine concentration-dependently reversed contraction of human prostate pre-contracted with 10 μM phenylephrine (-log IC(50) [M] 4.43 ± 0.08). Similar inhibition was observed in porcine trigone (-log IC(50) 5.01 ± 0.05), and in additional experiments consisted mainly of reduced maximum phenylephrine responses. At concentrations ≥1 μM, the propiverine metabolite M-14 also relaxed phenylephrine pre-contracted trigone strips, whereas metabolites M-5 and M-6 were ineffective. In radioligand binding experiments, propiverine and M-14 exhibited similar affinity for the three α(1)-adrenoceptor subtypes with -log K (i) [M] values ranging from 4.72 to 4.94, whereas the M-5 and M-6 did not affect [(3)H]-prazosin binding. In CHO cells, propiverine inhibited α(1)-adrenoceptor-mediated Ca(2+) elevations with similar potency as radioligand binding, again mainly by reducing maximum responses. In contrast to other muscarinic receptor antagonists, propiverine exerts additional L-type Ca(2+)-channel blocking and α(1)-adrenoceptor antagonist effects. It remains to be determined clinically, how these additional properties contribute to the clinical effects of propiverine, particularly in male voiding dysfunctio

    Synthesis, complex stability and small animal PET imaging of a novel 64Cu-labelled cryptand molecule

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    The radiosynthesis and radiopharmacological evaluation including small animal PET imaging of a novel 64Cu-labelled cryptand molecule ([64Cu]CryptTM) possessing a tris-pyridyl/tris-amido set of donor atoms is described

    Gene network analysis of Arabidopsis thaliana flower development through dynamic gene perturbations

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    Understanding how flowers develop from undifferentiated stem cells has occupied developmental biologists for decades. Key to unraveling this process is a detailed knowledge of the global regulatory hierarchies that control developmental transitions, cell differentiation and organ growth. These hierarchies may be deduced from gene perturbation experiments, which determine the effects on gene expression after specific disruption of a regulatory gene. Here, we tested experimental strategies for gene perturbation experiments during Arabidopsis thaliana flower development. We used artificial miRNAs (amiRNAs) to disrupt the functions of key floral regulators, and expressed them under the control of various inducible promoter systems that are widely used in the plant research community. To be able to perform genome‐wide experiments with stage‐specific resolution using the various inducible promoter systems for gene perturbation experiments, we also generated a series of floral induction systems that allow collection of hundreds of synchronized floral buds from a single plant. Based on our results, we propose strategies for performing dynamic gene perturbation experiments in flowers, and outline how they may be combined with versions of the floral induction system to dissect the gene regulatory network underlying flower development

    Évolution actuelle (1960-2021) de l’enneigement dans les Vosges à l’aide du modèle régional du climat MAR

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    peer reviewedL’évolution actuelle de l’enneigement dans les Vosges (N-E de la France) a été simulée à une résolution de 4 km avec le modèle régional du climat MAR (version 3.13) forcé par les réanalyses ERA5. Moyennant un petit ajustement de seulement 3 paramètres (dont 1 °C d’augmentation du seuil de température neige/pluie), MAR a été optimisé et validé sur 5 et 8 hivers (DJF) par rapport à des observations quotidiennes (température, précipitation, hauteur de neige). Sur les 62 hivers (DJF) 1960-2021, MAR suggère une diminution significative statistiquement d’environ un facteur deux de la hauteur moyenne de neige, due à l’augmentation significative des températures (~+2 °C/62 ans). Bien que les précipitations aient légèrement augmenté (+10-20 %/62 ans) à cause d’un renforcement (non significatif) de la circulation d’ouest, elles tombent de plus en plus sous forme de pluie, en particulier en dessous de 1000 m. Au-dessus de 1000 m, il ne neige pas moins qu’avant mais il y a plus de fonte réduisant le manteau neigeux entre deux événements neigeux. En extrapolant les tendances actuelles, une anomalie de +2.5 °C (resp. +3.8 °C) par rapport aux hivers 1960-90 serait suffisante pour ne plus avoir de neige en moyenne en-dessous de 750 m (resp. 1000 m)

    Orchestration of Floral Initiation by APETALA1

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    The MADS-domain transcription factor APETALA1 (AP1) is a key regulator of Arabidopsis flower development. To understand the molecular mechanisms underlying AP1 function, we identified its target genes during floral initiation using a combination of gene expression profiling and genome-wide binding studies. Many of its targets encode transcriptional regulators, including known floral repressors. The latter genes are down-regulated by AP1, suggesting that it initiates floral development by abrogating the inhibitory effects of these genes. Although AP1 acts predominantly as a transcriptional repressor during the earliest stages of flower development, at more advanced stages it also activates regulatory genes required for floral organ formation, indicating a dynamic mode of action. Our results further imply that AP1 orchestrates floral initiation by integrating growth, patterning, and hormonal pathways

    Intrathecal B Cells in MS Have Significantly Greater Lymphangiogenic Potential Compared to B Cells Derived From Non-MS Subjects

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    Although B cell depletion is an effective therapy of multiple sclerosis (MS), the pathogenic functions of B cells in MS remain incompletely understood. We asked whether cerebrospinal fluid (CSF) B cells in MS secrete different cytokines than control-subject B cells and whether cytokine secretion affects MS phenotype. We blindly studied CSF B cells after their immortalization by Epstein-Barr Virus (EBV) in prospectively-collected MS patients and control subjects with other inflammatory-(OIND) or non-inflammatory neurological diseases (NIND) and healthy volunteers (HV). The pilot cohort (n = 80) was analyzed using intracellular cytokine staining (n = 101 B cell lines [BCL] derived from 35 out of 80 subjects). We validated differences in cytokine production in newly-generated CSF BCL (n = 207 BCL derived from subsequent 112 prospectively-recruited subjects representing validation cohort), using ELISA enhanced by objective, flow-cytometry-based B cell counting. After unblinding the pilot cohort, the immortalization efficiency was almost 5 times higher in MS patients compared to controls (p < 0.001). MS subjects' BCLs produced significantly more vascular endothelial growth factor (VEGF) compared to control BCLs. Progressive MS patients BCLs produced significantly more tumor necrosis factor (TNF)-α and lymphotoxin (LT)-α than BCL from relapsing-remitting MS (RRMS) patients. In the validation cohort, we observed lower secretion of IL-1β in RRMS patients, compared to all other diagnostic categories. The validation cohort validated enhanced VEGF-C production by BCL from RRMS patients and higher TNF-α and LT-α secretion by BCL from progressive MS. No significant differences among diagnostic categories were observed in secretion of IL-6 or GM-CSF. However, B cell secretion of IL-1β, TNF-α, and GM-CSF correlated significantly with the rate of accumulation of disability measured by MS disease severity scale (MS-DSS). Finally, all three cytokines with increased secretion in different stages of MS (i.e., VEGF-C, TNF-α, and LT-α) enhance lymphangiogenesis, suggesting that intrathecal B cells directly facilitate the formation of tertiary lymphoid follicles, thus compartmentalizing inflammation to the central nervous system
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