111 research outputs found
Resolving vertical and east-west horizontal motion from differential interferometric synthetic aperture radar : The L'Aquila earthquake
Analysis of surface coseismic displacement has already been obtained for the 6 April 2009 L'Aquila (central Italy) earthquake from differential interferometric synthetic aperture radar (DInSAR) data. Working jointly on ascending and descending DInSAR data makes for a step forward with respect to published preliminary estimates: we process data in order to retrieve a continuous displacement pattern, both in the vertical and horizontal directions, the latter being limited to the eastward component because of the low sensibility of the SAR images used to resolve northward motion. Our analysis provides new insights on the horizontal component of displacement, obtaining a clear picture of eastward displacement patterns over the epicentral area. This result is noteworthy, as until now little information has been available on horizontal displacement following normal-fault events in the central Apennines (Umbria-Marche, 1997, and L'Aquila, 2009), given the lack of dense GPS networks, the only available source of horizontal displacement data in this area. Inverted fault characteristics from such data also show noteworthy differences compared to previous studies, localizing the Paganica fault as the causative fault for the earthquake
Promising Non-cytotoxic Monosubstituted Chalcones to Target Monoamine Oxidase-B
A library of monosubstituted chalcones (1-17) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with 13 and 14 showing the best profiles. In particular, 13 exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B 13 binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas 14 is accommodated in the opposite way. The main conclusion of this cell biology, biochemistry, and structural study is to highlights 13 as a chalcone derivative that is worth consideration for the development of novel MAO-B-selective inhibitors for the treatment of neurodegenerative diseases
Broad targeting of resistance to apoptosis in cancer
Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer
Photoacclimation strategies in northeastern Atlantic seagrasses: Integrating responses across plant organizational levels
Seagrasses live in highly variable light environments and adjust to these variations by expressing acclimatory responses at different plant organizational levels (meadow, shoot, leaf and chloroplast level). Yet, comparative studies, to identify species' strategies, and integration of the relative importance of photoacclimatory adjustments at different levels are still missing. The variation in photoacclimatory responses at the chloroplast and leaf level were studied along individual leaves of Cymodocea nodosa, Zostera marina and Z. noltei, including measurements of variable chlorophyll fluorescence, photosynthesis, photoprotective capacities, non-photochemical quenching and D1-protein repair, and assessments of variation in leaf anatomy and chloroplast distribution. Our results show that the slower-growing C. nodosa expressed rather limited physiological and biochemical adjustments in response to light availability, while both species of faster-growing Zostera showed high variability along the leaves. In contrast, the inverse pattern was found for leaf anatomical adjustments in response to light availability, which were more pronounced in C. nodosa. This integrative plant organizational level approach shows that seagrasses differ in their photoacclimatory strategies and that these are linked to the species' life history strategies, information that will be critical for predicting the responses of seagrasses to disturbances and to accordingly develop adequate management strategies.Fundacao para a Ciencia e Tecnologia (FCT), Portugal [PTDC/MAR-EST/4257/2014
Effects of elevated seawater pCO2 on gene expression patterns in the gills of the green crab, Carcinus maenas
Background: The green crab Carcinus maenas is known for its high acclimation potential to varying environmental
abiotic conditions. A high ability for ion and acid-base regulation is mainly based on an efficient regulation
apparatus located in gill epithelia. However, at present it is neither known which ion transport proteins play a key
role in the acid-base compensation response nor how gill epithelia respond to elevated seawater pCO2 as
predicted for the future. In order to promote our understanding of the responses of green crab acid-base
regulatory epithelia to high pCO2, Baltic Sea green crabs were exposed to a pCO2 of 400 Pa. Gills were screened
for differentially expressed gene transcripts using a 4,462-feature microarray and quantitative real-time PCR.
Results: Crabs responded mainly through fine scale adjustment of gene expression to elevated pCO2. However, 2%
of all investigated transcripts were significantly regulated 1.3 to 2.2-fold upon one-week exposure to CO2 stress.
Most of the genes known to code for proteins involved in osmo- and acid-base regulation, as well as cellular stress
response, were were not impacted by elevated pCO2. However, after one week of exposure, significant changes
were detected in a calcium-activated chloride channel, a hyperpolarization activated nucleotide-gated potassium
channel, a tetraspanin, and an integrin. Furthermore, a putative syntaxin-binding protein, a protein of the
transmembrane 9 superfamily, and a Cl-/HCO3
- exchanger of the SLC 4 family were differentially regulated. These
genes were also affected in a previously published hypoosmotic acclimation response study.
Conclusions: The moderate, but specific response of C. maenas gill gene expression indicates that (1) seawater
acidification does not act as a strong stressor on the cellular level in gill epithelia; (2) the response to hypercapnia
is to some degree comparable to a hypoosmotic acclimation response; (3) the specialization of each of the
posterior gill arches might go beyond what has been demonstrated up to date; and (4) a re-configuration of gill
epithelia might occur in response to hypercapnia
Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine
[This corrects the article DOI: 10.1186/s13054-016-1208-6.]
Bidirectional fluxes of spermine across the mitochondrial membrane.
The polyamine spermine is transported into the
mitochondrial matrix by an electrophoretic mechanism
having as driving force the negative electrical membrane
potential (DW). The presence of phosphate increases
spermine uptake by reducingDpH and enhancingDW. The
transport system is a specific uniporter constituted by a
protein channel exhibiting two asymmetric energy barriers
with the spermine binding site located in the energy well
between the two barriers. Although spermine transport is
electrophoretic in origin, its accumulation does not follow
the Nernst equation for the presence of an efflux pathway.
Spermine efflux may be induced by different agents, such as
FCCP, antimycin A and mersalyl, able to completely or
partially reduce theDWvalue and, consequently, suppress
or weaken the force necessary to maintain spermine in the
matrix. However this efflux may also take place in normal
conditions when the electrophoretic accumulation of the
polycationic polyamine induces a sufficient drop inDWable
to trigger the efflux pathway. The release of the polyamine
is most probably electroneutral in origin and can take place
in exchange with protons or in symport with phosphate
anion. The activity of both the uptake and efflux pathways
induces a continuous cycling of spermine across the mitochondrial membrane, the rate of which may be prominent in imposing the concentrations of spermine in the inner and
outer compartment. Thus, this event has a significant role on
mitochondrial permeability transition modulation and consequently on the triggering of intrinsic apoptosis
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