39 research outputs found
Fibrocytes and the tissue niche in lung repair
Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases
Antidepressants of the Serotonin-Antagonist Type Increase Body Fat and Decrease Lifespan of Adult Caenorhabditis elegans
It was recently suggested that specific antidepressants of the serotonin-antagonist type, namely mianserin and methiothepin, may exert anti-aging properties and specifically extend lifespan of the nematode C.elegans by causing a state of perceived calorie restriction (Petrascheck M, Ye X, Buck LB: An antidepressant that extends lifespan in adult Caenorhabditis elegans; Nature, Nov 22, 2007;450(7169):553–6, PMID 18033297). Using the same model organism, we instead observe a reduction of life expectancy when employing the commonly used, standardized agar-based solid-phase assay while applying the same or lower concentrations of the same antidepressants. Consistent with a well-known side-effect of these compounds in humans, antidepressants not only reduced lifespan but also increased body fat accumulation in C. elegans reflecting the mammalian phenotype. Taken together and in conflict with previously published findings, we find that antidepressants of the serotonin-antagonist type not only promote obesity, but also decrease nematode lifespan
Recombinational Landscape and Population Genomics of Caenorhabditis elegans
Recombination rate and linkage disequilibrium, the latter a function of population genomic processes, are the critical parameters for mapping by linkage and association, and their patterns in Caenorhabditis elegans are poorly understood. We performed high-density SNP genotyping on a large panel of recombinant inbred advanced intercross lines (RIAILs) of C. elegans to characterize the landscape of recombination and, on a panel of wild strains, to characterize population genomic patterns. We confirmed that C. elegans autosomes exhibit discrete domains of nearly constant recombination rate, and we show, for the first time, that the pattern holds for the X chromosome as well. The terminal domains of each chromosome, spanning about 7% of the genome, exhibit effectively no recombination. The RIAILs exhibit a 5.3-fold expansion of the genetic map. With median marker spacing of 61 kb, they are a powerful resource for mapping quantitative trait loci in C. elegans. Among 125 wild isolates, we identified only 41 distinct haplotypes. The patterns of genotypic similarity suggest that some presumed wild strains are laboratory contaminants. The Hawaiian strain, CB4856, exhibits genetic isolation from the remainder of the global population, whose members exhibit ample evidence of intercrossing and recombining. The population effective recombination rate, estimated from the pattern of linkage disequilibrium, is correlated with the estimated meiotic recombination rate, but its magnitude implies that the effective rate of outcrossing is extremely low, corroborating reports of selection against recombinant genotypes. Despite the low population, effective recombination rate and extensive linkage disequilibrium among chromosomes, which are techniques that account for background levels of genomic similarity, permit association mapping in wild C. elegans strains
Ureteral mullerian carcinosarcoma (mixed mullerian tumor) associated with endometriosis occurring in a patient with a concentrated soy isoflavones supplementation
SCOPUS: ar.jinfo:eu-repo/semantics/publishe
JNJ-40255293, a Novel Adenosine A<sub>2A</sub>/A<sub>1</sub> Antagonist with Efficacy in Preclinical Models of Parkinson’s Disease
Adenosine A<sub>2A</sub> antagonists
are believed to have therapeutic
potential in the treatment of Parkinson’s disease (PD). We
have characterized the dual adenosine A<sub>2A</sub>/A<sub>1</sub> receptor antagonist JNJ-40255293 (2-amino-8-[2-(4-morpholinyl)ethoxy]-4-phenyl-5<i>H</i>-indeno[1,2-<i>d</i>]pyrimidin-5-one). JNJ-40255293
was a high-affinity (7.5 nM) antagonist at the human A<sub>2A</sub> receptor with 7-fold in vitro selectivity versus the human A<sub>1</sub> receptor. A similar A<sub>2A</sub>:A<sub>1</sub> selectivity
was seen in vivo (ED<sub>50</sub>’s of 0.21 and 2.1 mg/kg p.o.
for occupancy of rat brain A<sub>2A</sub> and A<sub>1</sub> receptors,
respectively). The plasma EC<sub>50</sub> for occupancy of rat brain
A<sub>2A</sub> receptors was 13 ng/mL. In sleep–wake encephalographic
(EEG) studies, JNJ-40255293 dose-dependently enhanced a consolidated
waking associated with a subsequent delayed compensatory sleep (minimum
effective dose: 0.63 mg/kg p.o.). As measured by microdialysis, JNJ-40255293
did not affect dopamine and noradrenaline release in the prefrontal
cortex and the striatum. However, it was able to reverse effects (catalepsy,
hypolocomotion, and conditioned avoidance impairment in rats; hypolocomotion
in mice) produced by the dopamine D<sub>2</sub> antagonist haloperidol.
The compound also potentiated the agitation induced by the dopamine
agonist apomorphine. JNJ-40255293 also reversed hypolocomotion produced
by the dopamine-depleting agent reserpine and potentiated the effects
of l-dihydroxyphenylalanine (L-DOPA) in rats with unilateral
6-hydroxydopamine-induced lesions of the nigro-striatal pathway, an
animal model of Parkinson’s disease. Extrapolating from the
rat receptor occupancy dose–response curve, the occupancy required
to produce these various effects in rats was generally in the range
of 60–90%. The findings support the continued research and
development of A<sub>2A</sub> antagonists as potential treatments
for PD