102 research outputs found
Thrombin in the peripheral nervous system as regulator of Schwann cell neurotrophic potentials
Coagulation and inflammation are tightly and reciprocally regulated. Inflammation initiates clotting, decreases the activity of natural anticoagulant mechanisms and impairs the fibrinolytic system. Thrombin is the main effector protease in hemostasis and it also plays a role in various non-hemostatic biological and pathophysiologic processes, predominantly mediated through activation of protease-activated receptors (PARs)
Nanocarbon surfaces for biomedicine
The distinctive physicochemical, mechanical and electrical
properties of carbon nanostructures are currently gaining
the interest of researchers working in bioengineering and
biomedical fields. Carbon nanotubes, carbon dendrimers, graphenic
platelets and nanodiamonds are deeply studied aiming
at their application in several areas of biology and medicine.
Here we provide a summary of the carbon nanomaterials
prepared in our labs and of the fabrication techniques used to
produce several biomedical utilities, from scaffolds for tissue
growth to cargos for drug delivery and to biosensors
Crucial role of androgen receptor in vascular H2S biosynthesis induced by testosterone.
BACKGROUND AND PURPOSE:
Hydrogen sulphide (H2S) is a gaseous mediator strongly involved in cardiovascular homeostasis, where it provokes vasodilation. Having previously shown that H2S contributes to testosterone (T) induced vasorelaxation, here we aim to uncover the mechanisms underlying this effect.
EXPERIMENTAL APPROACH:
H2S biosynthesis was evaluated in rat isolated aorta rings following androgen receptor (AR) stimulation. Co-immunoprecipitation and surface plasmon resonance analysis have been performed to investigate mechanisms involved in AR activation.
KEY RESULTS:
H2S biosynthesis is associated to activation of AR by testosterone or androgen agonist mesterolone and blocked by AR antagonist nilutamide. This event is linked to AR-multicomplex-derived heath shock protein 90 (hsp90), since its specific inhibitor geldanamycin strongly reduced T-induced H2S production. Neither progesterone nor 17-β-oestradiol actions did account for H2S release. Furthermore, we found that cystathionine gamma lyase (CSE), the main vascular H2S-synthesizing enzyme, is physically associated to AR/hsp90 complex and the generation of such a ternary system represents a key event leading to CSE activation. Finally, H2S levels in human blood collected from male healthy volunteers were higher than those observed in female samples.
CONCLUSIONS AND IMPLICATIONS:
Here, we demonstrated that selective activation of the AR is essential for H2S biosynthesis within vascular tissue and this event is based on formation of a ternary complex among CSE, AR and hsp90. This novel molecular mechanism operating in vascular district, corroborated by higher H2S level in males, suggested that L-cysteine/CSE/H2S pathway may be preferentially activated in males leading to a gender-related H2S biosynthesis
Detonation nanodiamonds tailor the structural oeder of PEDOT chains in conductive coating layers of hybrid nanoparticles
Solid layers of PEDOT–detonation nanodiamond based nanoparticles with an exceptional structural order
were produced by means of a template-free polymerization technique. As an efficient multifunctional filler,
the nanocrystalline diamond has been shown to possess a high catalytic activity on the monomer
polymerization rate as well as to play a fundamental role as a 3D arrangement-directing agent of the
PEDOT chains at the micro- and nano-scale. SEM, TEM and TED analyses highlighted the mutual
organization between PEDOT oligomers and nanodiamond grains, and the produced hierarchical effects
on the arrangement of the backbones of the final polymer. Optical and Raman spectroscopy, used
together with XRD diffraction to study the molecular structure and crystallographic features of the hybrid
materials, pointed out that the adopted synthetic strategy enables highly conjugated and doped hybrid
systems to be generated. The spatial distribution of the filler inside the polymeric matrix and the mutual
connectivity of nanodiamond crystals and PEDOT segments are found to strongly improve the functional
properties of the host polymer. Mechanical characterizations by advanced AFM-based techniques
revealed that both indentation modulus and hardness of PEDOT/nanodiamond materials are 3 times
higher than the pure PEDOT polymer, while electrical characterizations by a 4-probe method gave sheet
resistance values of 1 106 U sq 1 for the nanocomposite particle
TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: Relevance in human colorectal tumors
TNF receptor-associated protein 1 (TRAP1) is an HSP90 chaperone involved in stress protection and apoptosis in mitochondrial and extramitochondrial compartments. Remarkably, aberrant deregulation of TRAP1 function has been observed in several cancer types with potential new opportunities for therapeutic intervention in humans. Although previous studies by our group identified novel roles of TRAP1 in quality control of mitochondria-destined proteins through the attenuation of protein synthesis, molecular mechanisms are still largely unknown. To shed further light on the signaling pathways regulated by TRAP1 in the attenuation of protein synthesis, this study demonstrates that the entire pathway of cap-mediated translation is activated in cells following TRAP1 interference: consistently, expression and consequent phosphorylation of p70S6K and RSK1, two translation activating kinases, are increased upon TRAP1 silencing. Furthermore, we show that these regulatory functions affect the response to translational stress and cell migration in wound healing assays, processes involving both kinases. Notably, the regulatory mechanisms controlled by TRAP1 are conserved in colorectal cancer tissues, since an inverse correlation between TRAP1 and p70S6K expression is found in tumor tissues, thereby supporting the relevant role of TRAP1 translational regulation in vivo. Taken as a whole, these new findings candidate TRAP1 network for new anti-cancer strategies aimed at targeting the translational/quality control machinery of tumor cells
Kinematics of a relativistic particle with de Sitter momentum space
We discuss kinematical properties of a free relativistic particle with
deformed phase space in which momentum space is given by (a submanifold of) de
Sitter space. We provide a detailed derivation of the action, Hamiltonian
structure and equations of motion for such free particle. We study the action
of deformed relativistic symmetries on the phase space and derive explicit
formulas for the action of the deformed Poincare' group. Finally we provide a
discussion on parametrization of the particle worldlines stressing analogies
and differences with ordinary relativistic kinematics.Comment: RevTeX, 12 pages, no figure
TRAP1 regulates stemness through Wnt/β-catenin pathway in human colorectal carcinoma
Colorectal carcinoma (CRC) is a common cause of cancer-related death worldwide. Indeed, treatment failures are triggered by cancer stem cells (CSCs) that give rise to tumor repopulation upon initial remission. Thus, the role of the heat shock protein TRAP1 in stemness was investigated in CRC cell lines and human specimens, based on its involvement in colorectal carcinogenesis, through regulation of apoptosis, protein homeostasis and bioenergetics. Strikingly, co-expression between TRAP1 and stem cell markers was observed in stem cells located at the bottom of intestinal crypts and in CSCs sorted from CRC cell lines. Noteworthy, TRAP1 knockdown reduced the expression of stem cell markers and impaired colony formation, being the CSC phenotype and the anchorage-independent growth conserved in TRAP1-rich cancer cells. Consistently, the gene expression profiling of HCT116 cells showed that TRAP1 silencing results in the loss of the stem-like signature with acquisition of a more-differentiated phenotype and the downregulation of genes encoding for activating ligands and target proteins of Wnt/β-catenin pathway. Mechanistically, TRAP1 maintenance of stemness is mediated by the regulation of Wnt/β-catenin signaling, through the modulation of the expression of frizzled receptor ligands and the control of β-catenin ubiquitination/phosphorylation. Remarkably, TRAP1 is associated with higher expression of β-catenin and several Wnt/β-catenin target genes in human CRCs, thus supporting the relevance of TRAP1 regulation of β-catenin in human pathology. This study is the first demonstration that TRAP1 regulates stemness and Wnt/β-catenin pathway in CRC and provides novel landmarks in cancer biology and therapeutics
Seasonality of nitrogen sources, cycling, and loading in a New England river discerned from nitrate isotope ratios
Coastal waters globally are increasingly impacted due to the anthropogenic
loading of nitrogen (N) from the watershed. To assess dominant sources
contributing to the eutrophication of the Little Narragansett Bay estuary in
New England, we carried out an annual study of N loading from the Pawcatuck
River. We conducted weekly monitoring of nutrients and nitrate
(NO3-) isotope ratios (15N / 14N, 18O / 16O, and
17O / 16O) at the mouth of the river and from the larger of two
wastewater treatment facilities (WWTFs) along the estuary, as well as
seasonal along-river surveys. Our observations reveal a direct relationship
between N loading and the magnitude of river discharge and a consequent
seasonality to N loading into the estuary – rendering loading from the
WWTFs and from an industrial site more important at lower river flows during
warmer months, comprising ∼ 23 % and ∼ 18 % of N loading,
respectively. Riverine nutrients derived predominantly from deeper
groundwater and the industrial point source upriver in summer and from
shallower groundwater and surface flow during colder months – wherein
NO3- associated with deeper groundwater had higher
15N / 14N ratios than shallower groundwater. Corresponding
NO3- 18O / 16O ratios were lower during the warm season,
due to increased biological cycling in-river. Uncycled atmospheric
NO3-, detected from its unique mass-independent NO3-
17O / 16O vs. 18O / 16O fractionation, accounted for
< 3 % of riverine NO3-, even at elevated discharge.
Along-river, NO3- 15N / 14N ratios showed a correspondence
to regional land use, increasing from agricultural and forested catchments
to the more urbanized watershed downriver. The evolution of
18O / 16O isotope ratios along-river conformed to the notion of
nutrient spiraling, reflecting the input of NO3- from the
catchment and from in-river nitrification and its coincident removal by
biological consumption. These findings stress the importance of considering
seasonality of riverine N sources and loading to mitigate eutrophication in
receiving estuaries. Our study further advances a conceptual framework that
reconciles with the current theory of riverine nutrient cycling, from which
to robustly interpret NO3- isotope ratios to constrain cycling and
source partitioning in river systems.</p
M-CSF Induces Monocyte Survival by Activating NF-κB p65 Phosphorylation at Ser276 via Protein Kinase C
Macrophage colony-stimulating factor (M-CSF) promotes mononuclear phagocyte survival and proliferation. The transcription factor Nuclear Factor-kappaB (NF-κB) is a key regulator of genes involved in M-CSF-induced mononuclear phagocyte survival and this study focused at identifying the mechanism of NF-κB transcriptional activation. Here, we demonstrate that M-CSF stimulated NF-κB transcriptional activity in human monocyte-derived macrophages (MDMs) and the murine macrophage cell line RAW 264.7. The general protein kinase C (PKC) inhibitor Ro-31-8220, the conventional PKCα/β inhibitor Gö-6976, overexpression of dominant negative PKCα constructs and PKCα siRNA reduced NF-κB activity in response to M-CSF. Interestingly, Ro-31-8220 reduced Ser276 phosphorylation of NF-κBp65 leading to decreased M-CSF-induced monocyte survival. In this report, we identify conventional PKCs, including PKCα as important upstream kinases for M-CSF-induced NF-κB transcriptional activation, NF-κB-regulated gene expression, NF-κB p65 Ser276 phosphorylation, and macrophage survival. Lastly, we find that NF-κB p65 Ser276 plays an important role in basal and M-CSF-stimulated NF-κB activation in human mononuclear phagocytes
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