175 research outputs found
Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA
Transformation of murine thymocytes by
radiation leukemia virus is associated with reduced expression
of the class I antigens encoded in the major histocompatibility
complex (MHC) and increased methylation and altered restriction
enzyme patterns of MHC DNA. These changes may play
a role in host susceptibility to virus-induced leukemogenesis
and accord with the notion that viral genomes play a regulatory
function when they integrate adjacent to histocompatibiity
genes
Transcriptomic and proteomic insight into the effects of a defined European mistletoe extract in Ewing sarcoma cells reveals cellular stress responses
Background The hydrophobic triterpenes, oleanolic and betulinic acid as well
as the hydrophilic mistletoe lectins and viscotoxins possess anticancer
properties. They do all occur in combination in European mistletoe (Viscum
album L.). Commercial Viscum album L. extracts are aqueous, excluding the
insoluble triterpenes. We have previously shown that mistletoe lectins and
triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in
vivo. Methods We recreated a total mistletoe effect (viscumTT) by combining an
aqueous extract (viscum) and a triterpene extract (TT) solubilised with
cyclodextrins and analysed the effects of viscumTT and the single extracts on
TC-71 Ewing sarcoma cells in vitro by transcriptomic and proteomic profiling.
Results Treatment with the extracts strongly impacted Ewing sarcoma cell gene
and protein expression. Apoptosis-associated and stress-activated genes were
upregulated, proteasomal protein abundance enhanced and ribosomal and
spliceosomal proteins downregulated. The mechanism of action of viscum, TT and
viscumTT in TC-71 and MHH-ES-1 cells suggests the involvement of the unfolded
protein response. While viscum and viscumTT extract treatment indicate
response to oxidative stress and activation of stress-mediated MAPK
signalling, TT extract treatment suggests the involvement of TLR signalling
and autophagy. Conclusions Since the combinatory extract viscumTT exerts
highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this
phytopolychemotherapy could be a promising adjuvant therapeutic option for
paediatric patients with Ewing sarcoma
The Parameterized Complexity of Centrality Improvement in Networks
The centrality of a vertex v in a network intuitively captures how important
v is for communication in the network. The task of improving the centrality of
a vertex has many applications, as a higher centrality often implies a larger
impact on the network or less transportation or administration cost. In this
work we study the parameterized complexity of the NP-complete problems
Closeness Improvement and Betweenness Improvement in which we ask to improve a
given vertex' closeness or betweenness centrality by a given amount through
adding a given number of edges to the network. Herein, the closeness of a
vertex v sums the multiplicative inverses of distances of other vertices to v
and the betweenness sums for each pair of vertices the fraction of shortest
paths going through v. Unfortunately, for the natural parameter "number of
edges to add" we obtain hardness results, even in rather restricted cases. On
the positive side, we also give an island of tractability for the parameter
measuring the vertex deletion distance to cluster graphs
Age impairs soluble guanylyl cyclase function in mouse mesenteric arteries
Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography. Acetylcholine (ACh)-induced relaxation was reduced in aged as compared to juvenile vessels. Pretreatment with L-NAME, which inhibits nitrix oxide synthases (NOS), decreased ACh-mediated vasorelaxation, whereby differences in vasorelaxation between groups disappeared. Endothelium-independent vasorelaxation by the NO donor sodium nitroprusside (SNP) was similar in both groups; however, SNP bolus application (10(-6) mol L(-1)) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10(-6) mol L(-1)) caused faster responses in juvenile vessels. This was accompanied by higher cGMP concentrations and a stronger response to the PDE5 inhibitor sildenafil in juvenile vessels. Mesenteric arteries and aortas did not reveal apparent histological differences between groups (van Gieson staining). The mRNA expression of the α1 and α2 subunits of sGC was lower in aged animals, as was PDE5 mRNA expression. In conclusion, vasorelaxation is compromised at an early age in mice even in the absence of histopathological alterations. Vascular smooth muscle sGC is a key element in aged vessel dysfunction
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