Search results for "Cascade"
showing 10 items of 271 documents
Role of the HIPPO pathway as potential key player in the cross talk between oncology and cardiology.
2021
The HIPPO pathway (HP) is a highly conserved kinase cascade that affects organ size by regulating proliferation, cell survival and differentiation. Discovered in Drosophila melanogaster to early 2000, it immediately opened wide frontiers in the field of research. Over the last years the field of knowledge on HP is quickly expanding and it is thought will offer many answers on complex pathologies. Here, we summarized the results of several studies that have investigated HP signaling both in oncology than in cardiology field, with an overview on future perspectives in cardiology research.
Amyloid in Alzheimer’s Disease: Guilty Beyond Reasonable Doubt?
2017
Recently failed antiamyloidogenic trials call for an objective reassessment of the dominating amyloid cascade hypothesis of Alzheimer's disease (AD). Ongoing efforts focusing on amyloid β protein (Aβ), its deposition, and its removal need to be complemented by more intensive research in new directions. Those may either integrate amyloid pathology or will propose pathogenetic routes independent of Aβ in the search for the causes of AD.
Sustained oscillations in the MAP kinase cascade.
2016
Abstract The MAP kinase cascade is a network of enzymatic reactions arranged in layers. In each layer occurs a multiple futile cycle of phosphorylations. The fully phosphorylated substrate then serves as an enzyme for the layer below. This paper focuses on the existence of parameters for which Hopf bifurcations occur and generate periodic orbits. Furthermore it is explained how geometric singular perturbation theory allows to generalize results from simple models to more complex ones.
The search for novel targets in Alzheimer's disease—The 90s redux
2021
Alzheimer's disease (AD) is a complex disease of the brain. Despite over 100 years of basic and clinical research, significantly intensified in the last three decades, the exact cause of this neurodegeneration is still an enigma. Based on neuroanatomical, experimental, and clinical findings, a series of hypotheses on AD pathogenesis have evolved. Among them, the "amyloid cascade hypothesis" has been most prominent. Clinical efforts targeting the biochemistry of amyloid β-protein (Aβ) as causal therapy have all failed so far, which may mean that the pathogenic mechanism of AD is less straightforward than initially thought. While there was good scientific reason to support this hypothesis bef…
The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells.
2016
Activated pancreatic stellate cells (PaSC) are key participants in the stroma of pancreatic cancer, secreting extracellular matrix proteins and inflammatory mediators. Tumors are poorly vascularized, creating metabolic stress conditions in cancer and stromal cells that necessitate adaptive homeostatic cellular programs. Activation of autophagy and the endoplasmic reticulum unfolded protein response (UPR) have been described in hepatic stellate cells, but the role of these processes in PaSC responses to metabolic stress is unknown. We reported that the PI3K/mTOR pathway, which AMPK can regulate through multiple inputs, modulates PaSC activation and fibrogenic potential. Here, using primary a…
Measurement of the AtmosphericνeSpectrum with IceCube
2015
We present a measurement of the atmospheric $\nu_e$ spectrum at energies between 0.1 TeV and 100 TeV using data from the first year of the complete IceCube detector. Atmospheric $\nu_e$ originate mainly from the decays of kaons produced in cosmic-ray air showers. This analysis selects 1078 fully contained events in 332 days of livetime, then identifies those consistent with particle showers. A likelihood analysis with improved event selection extends our previous measurement of the conventional $\nu_e$ fluxes to higher energies. The data constrain the conventional $\nu_e$ flux to be $1.3^{+0.4}_{-0.3}$ times a baseline prediction from a Honda's calculation, including the knee of the cosmic-…
Factors controlling planktonic size spectral responses to autumnal circulation in a Mediterranean lake
2006
14 pages, and figures, and tables statistics.
Bacterial community response to changes in a tri-trophic cascade during a whole-lake fish manipulation
2015
Microbial communities play a key role in biogeochemical processes by degrading organic material and recycling nutrients, but can also be important food sources for upper trophic levels. Trophic cascades might modify microbial communities either directly via grazing or indirectly by inducing changes in other biotic or in abiotic factors (e.g., nutrients). We studied the effects of a tri-trophic cascade on microbial communities during a whole-lake manipulation in which European perch (Perca fluviatilis) were added to a naturally fishless lake divided experimentally into two basins. We measured environmental parameters (oxygen, temperature, and nutrients) and zooplankton biomass and studied th…
New Fluorinated Peptidomimetics through Tandem Aza-Michael Addition to α-Trifluoromethyl Acrylamide Acceptors: Synthesis and Conformational Study in …
2009
A range of partially modified retro (PMR) psi[NHCH(2)] peptide mimetics containing a hydrolytically stable CH(2)CH(CF(3))CO unit have been synthesized. The first kind of peptidomimetics is obtained from the highly efficient aza-Michael addition of different amines to alpha-trifluoromethyl acrylamide acceptors. Subsequent deprotection of the amino group furnishes the key common intermediate for the synthesis of other families of peptidomimetics: dipeptides, tripeptides, peptidomimetics containing a urea moiety, and structures containing two units of alpha-trifluoromethyl-beta(2)-alanine. Finally, a conformational study of several of the newly synthesized peptidomimetics, performed with the a…