Hyaluronan (HA) is one of the most prevalent glycosaminoglycans of the vascular extracellular matrix (ECM). Abnormal HA accumulation within blood vessel walls is associated with tissue inflammation ...and is prominent in most vascular pathological conditions such as atherosclerosis and restenosis. Hyaluronan synthase 2 (HAS2) is the main hyaluronan synthase enzyme involved in HA synthesis and uses cytosolic UDP-glucuronic acid and UDP-GlcNAc as substrates. The synthesis of UDP-glucuronic acid can alter the NAD+/NADH ratio via the enzyme UDP-glucose dehydrogenase, which oxidizes the alcohol group at C6 to the COO− group. Here, we show that HAS2 expression can be modulated by sirtuin 1 (SIRT1), the master metabolic sensor of the cell, belonging to the class of NAD+-dependent deacetylases. Our results revealed the following. 1) Treatments of human aortic smooth muscle cells (AoSMCs) with SIRT1 activators (SRT1720 and resveratrol) inhibit both HAS2 expression and accumulation of pericellular HA coats. 2) Tumor necrosis factor α (TNFα) induced HA-mediated monocyte adhesion and AoSMC migration, whereas SIRT1 activation prevented immune cell recruitment and cell motility by reducing the expression levels of the receptor for HA-mediated motility, RHAMM, and the HA-binding protein TNF-stimulated gene 6 protein (TSG6). 3) SIRT1 activation prevented nuclear translocation of NF-κB (p65), which, in turn, reduced the levels of HAS2–AS1, a long-noncoding RNA that epigenetically controls HAS2 mRNA expression. In conclusion, we demonstrate that both HAS2 expression and HA accumulation by AoSMCs are down-regulated by the metabolic sensor SIRT1.
Hyaluronan is a glycosaminoglycan normally present in the extracellular matrix in most tissues. Hyaluronan is a crucial player in many processes associated with cancer, such as angiogenesis, ...invasion, and metastasis. However, little has been reported regarding the action of hyaluronan on monocytes/macrophages (Mo/MØ) in tumor angiogenesis and its consequences on tumor development. In the present study, we investigated the effects of hyaluronan of different sizes on human Mo/MØ angiogenic behavior in colorectal and breast carcinoma. In vitro, the treatment of Mo/MØ with lysates and conditioned media from a breast but not from colorectal carcinoma cell line plus high‐molecular weight hyaluronan induced: (a) an increased expression of angiogenic factors VEGF, IL‐8, FGF‐2, and MMP‐2, (b) an increased endothelial cell migration, and (c) a differential expression of hyaluronan‐binding protein TSG‐6. Similar results were observed in Mo/MØ derived from breast cancer patients treated with tumor lysates. Besides, macrophages primed with high‐molecular weight hyaluronan and inoculated in human breast cancer xenograft tumor increased blood vessel formation and diminished TSG‐6 levels. In contrast, the effects triggered by high‐molecular weight hyaluronan on Mo/MØ in breast cancer context were not observed in the context of colorectal carcinoma. Taken together, these results indicate that the effect of high‐molecular weight hyaluronan as an inductor of the angiogenic behavior of macrophages in breast tumor context is in part consequence of the presence of TSG‐6.
Hyaluronan is a crucial player in many processes associated with cancer. Here, we investigated the action of hyaluronan (high‐ or low‐molecular weight) on monocytes/macrophages (Mo/MØ) in different tumor contexts. Our findings suggest that treatment with high‐molecular weight hyaluronan modulates TSG‐6 protein levels and increases the angiogenic behavior of Mo/MØ in the context of breast but not of colorectal carcinoma.
Professional organizations that oversee the accreditation of graduate training programs in behavior analysis have increased didactic training requirements for programs in various domains across the ...years. One of the areas in which this has occurred concerns training in philosophy within behavior science. Although content-hour requirements for didactic philosophical training have increased, the contents of this training are not prescribed and are left to the discretion of individual programs. We conducted a survey of verified course sequence programs to assess the current state of training in philosophy in behavior analysis graduate training programs. The results provided a list of common topics and readings in philosophy courses, and indicated an emphasis on radical behaviorism and the works of B. F. Skinner. The list of topics and readings obtained provides a resource for course design, and we suggest that exposing students to a broader range of behavioristic and nonbehavioristic topics and readings may enhance students’ orientation to philosophical issues in behavior analysis.
We assessed the contribution of leaf movements to PSII photoprotection against high light and temperature in Robinia pseudoacacia. Gas exchange and chlorophyll a fluorescence measurements were ...performed during the day at 10:00, 12:00, 15:00 and 18:00 hours on leaves where paraheliotropic movements were restrained (restrained leaves, RL) and on control unrestrained leaves (UL). RL showed a strong decrease of net photosynthesis (A(n)), stomatal conductance (g(sH2O)), quantum yield of electron transport (PhiPSII), percentage of photosynthesis inhibited by O2 (IPO) and photochemical quenching (q(P)) in the course of the day, whereas, a significant increase in C(i)/C(a) and NPQ was observed. Contrary to RL, UL had higher photosynthetic performance that was maintained at elevated levels throughout the day. In the late afternoon, A(n), g(sH2O), PhiPSII and q(P) of RL showed a tendency to recovery, as compared to 15:00 hours, even if the values remained lower than those measured at 10:00 hours and in UL. In addition, contrary to UL, no recovery was found in F(v)/F(m) at the end of the study period in RL. Data presented suggest that in R. pseudoacacia, leaf movements, by reducing light interception, represent an efficient, fast and reversible strategy to overcome environmental stresses such as high light and temperature. Moreover, paraheliotropism was able to protect photosystems, avoiding photoinhibitory damage, leading to a carbon gain for the plant.
Hyaluronan (HA) is a component of the extracellular matrix (ECM) it is the main non‐sulfated glycosaminoglycan able to modulate cell behavior in the healthy and tumor context. Sulfated hyaluronan ...(sHA) is a biomaterial derived from chemical modifications of HA, since this molecule is not naturally sulfated. The HA sulfation modifies several properties of the native molecule, acquiring antitumor properties in different cancers. In this study, we evaluated the action of sHA of ~30–60 kDa with different degrees of sulfation (0.7 sHA1 and 2.5 sHA3) on tumor cells of a breast, lung, and colorectal cancer model and its action on other cells of the tumor microenvironment, such as endothelial and monocytes/macrophage cells. Our data showed that in breast and lung tumor cells, sHA3 is able to modulate cell viability, cytotoxicity, and proliferation, but no effects were observed on colorectal cancer cells. In 3D cultures of breast and lung cancer cells, sHA3 diminished the size of the tumorsphere and modulated total HA levels. In these tumor models, treatment of monocytes/macrophages with sHA3 showed a downregulation of the expression of angiogenic factors. We also observed a decrease in endothelial cell migration and modulation of the hyaluronan‐binding protein TSG‐6. In the breast in vivo xenograft model, monocytes/macrophages preincubated with sHA1 or sHA3 decreased tumor vasculature, TSG‐6 and HA levels. Besides, in silico analysis showed an association of TSG‐6, HAS2, and IL‐8 with biological processes implicated in the progression of the tumor. Taken together, our data indicate that sHA in a breast and lung tumor context is able to induce an antiangiogenic action on tumor cells as well as in monocytes/macrophages (Mo/MØ) by modulation of endothelial migration, angiogenic factors, and vessel formation.
The global climate is predicted to change in the next century; for the Mediterranean Basin, an increase in air temperature more than 4°C and a higher frequency of extreme climatic events such as ...drought and heat waves are expected. In this work, the response of Cistus salvifolius L. to the rise in winter temperature has been studied. Plants acclimated to winter conditions outdoor (OUT) were moved into a greenhouse indoor (IND) at higher temperature and eco-physiological behaviour was analysed on leaves after 15 days from plant transferring (IND ₁₅d) and on leaves developed IND. IND leaves were characterized by reduced thickness, higher specific leaf area, higher CO ₂ mesophyll conductance and photosynthetic rate, and lower respiratory rate than leaves grown OUT upon current winter conditions. In IND ₁₅d leaves, no improvement of photochemical activity was found. When IND leaves were subjected to a rapid increase in air temperature, the CO ₂ fixation was not limited indicating a high thermotolerance of photosynthetic machinery. The results for IND leaves indicate the occurrence of a strategy that merging changes in leaf structure as well as in photosynthetic regulation allow C. salvifolius to maintain an elevated carbon gain in response to temperature increase.
Hyaluronan is the major glycosaminoglycan present in the extracellular matrix of several cell types; its synthesis occurs on the cellular plasma membrane. Variations in its expression are related to ...alterations in cell proliferation, adhesion, and migration. It is able to interact with different binding proteins called hyaladherins, which can be conjugated to different fluorochromes and analyzed by flow cytometry.
The performance of niobium pentoxide (Nb
2
O
5
) as photoanodes in dye-sensitized solar cells (DSSCs) and as catalysts in the photocatalytic degradation of Rhodamine B (RhB) was investigated. Four ...samples of Nb
2
O
5
(Nb
2
O
5
_SG, Nb
2
O
5
_CR, Nb
2
O
5
_PP, and Nb
2
O
5
_MA) were synthesized by four different methods, respectively, entailing the sol-gel, combustion, polymeric precursors, and a microwave-assisted hydrothermal reaction. In all these samples, the orthorhombic phase of Nb
2
O
5
was obtained, which resulted in different shapes and assemblies, which is very relevant because the surface area, shape, and size distribution of the nanoparticles significantly contribute to the optical process. The bandgap remained constant at 3.0 eV for all the samples, even for the sample prepared by the combustion method. An additional phase, which is related to local distortions, was revealed by Raman spectroscopy within the vibration range of 688–260 cm
−1
. DSSCs using photoanodes with smaller and more dispersed Nb
2
O
5
particles showed better results than those with inhomogeneities. For comparison, DSSCs were assembled using two different counter electrodes, platinum and graphite. The DSSC with platinum showed better photovoltaic results, mainly with photocurrents from 1.17 mA.cm
−2
for Nb
2
O
5
_CR to 1.64 mA.cm
−2
for Nb
2
O
5
_SG. The same trend was observed for the photocatalytic degradation of RhB, where the smaller and dispersed particles of Nb
2
O
5
_CR and Nb
2
O
5
_SG exhibited the best performance and, respectively, degraded approximately 75% and 61% of the RhB dye over 180 min. Therefore, the results of this study established a correlation between the synthesis methods and photonic behavior.
Graphical abstract
This research aimed to investigate the physiological strategies that allow Phillyrea angustifolia, a sclerophyllous shrub widespread in the Mediterranean maquis, to cope successfully with the most ...stressful conditions of the Mediterranean climate i.e. summer drought and winter cold. Gas exchange and chlorophyll a fluorescence measurements as well as pigment content determinations were performed periodically throughout one whole year (spring 2004–spring 2005) on plants growing outdoor in the Botanical Garden of the Naples University. In June and July 2004 and in February 2005 the light-saturated net photosynthetic rate (PN) and stomatal conductance (gH₂O) were lower compared to May and October 2004. Carboxylation rate (vc) was negatively affected by summer drought and low temperature. The quantum yield (ΦPSII) and maximum photochemical efficiency of PSII (Fᵥ/Fₘ) significantly declined in February. All monitored parameters increased after each stressful period. The highest carotenoid content was detected in July whereas total pigment content was lower both in July and in February as compared to May and October, respectively. The photosynthetic apparatus of P. angustifolia is able to cope with summer drought and winter cold by different strategies: in summer, efficient stomatal control reduces water loss whereas in winter, PSII efficiency is down-regulated to avoid irreversible damage.
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