Expression and involvement of c-fos and c-jun protooncogenes in programmed cell death induced by growth factor deprivation in lymphoid cell lines

Cell death induced by growth factor withdrawal is a programed event in which gene transcription and translation are required. Thus, it is likely that genes encoding for transcriptional factors can play an important role in this process. We have tested this hypothesis by analyzing c-fos and c-jun protooncogene expression and involvement in lymphoid cells deprived of growth factors. Interleukin (IL)-6- and IL-2-dependent mouse cell lines undergo programmed cell death after growth factor deprivation. Northern blot analysis shows that c-fos and c-jun protooncogenes are rapidly induced (within 60 min) after growth factor deprivation in IL-6- and IL-2-dependent mouse cells. Induction is transient, being undetectable at 120 min after deprivation. Induction of these protooncogenes is at the transcriptional level, as demonstrated by actinomycin D and nuclear run-off experiments. Antisense oligonucleotides directed against c-fos and c-jun mRNAs consistently reduced the expression of these genes in treated cells. This reduction was associated with increased survival of growth factor-deprived lymphoid cells, thus suggesting that the expression of c-fos and c-jun protooncogenes may represent an important early event in the activation of the genetic program of cell death

Effect of pressure on octahedral distortions in RCrO3 (R = Lu, Tb, Gd, Eu, Sm): The role of R-ion size and its implications

The effect of rare-earth ion size on the octahedral distortions in rare-earth chromites (RCrO3, R = Lu, Tb, Gd, Eu, Sm) crystallizing in the orthorhombic structure has been studied using Raman scattering and synchrotron powder x-ray diffraction up to 20 GPa. From our studies on RCrO3 we found that the octahedral tilts (distortions) increase with pressure. This is contrary to the earlier report which suggests that in LaCrO3, the distortions decrease with pressure leading to a more ordered phase at high pressure. Here we observe that the rate of increase in distortion decreases with the increase in R-ion radii. This occurs due to the reduction in the compression of RO12 polyhedra with a corresponding increase in the compression of the CrO6 octahedra with increasing R-ion radii. From the Raman studies, we predict a critical R-ion radii, above which we expect the distortions in RCrO3 to reduce with increasing pressure leading to what is observed in the case of LaCrO3. These Raman results are consistent with our pressure dependent structural studies on RCrO3 (R = Gd, Eu, Sm). Also, our results suggest that the pressure dependence of N\'eel temperature, TNCr, (where the Cr3+ spin orders) in RCrO3 is mostly affected by the compressions of Cr-O bonds rather than the alteration of octahedral tilts.Comment: 17 pages, 8 figures This manuscript has been published in Material Research Expres

Self-Assembly and Gelation Study of Dipeptide Isomers with Norvaline and Phenylalanine

Dipeptides have emerged as attractive building blocks for supramolecular materials thanks to their low-cost, inherent biocompatibility, ease of preparation, and environmental friendliness as they do not persist in the environment. In particular, hydrophobic amino acids are ideal candidates for self-assembly in polar and green solvents, as a certain level of hydrophobicity is required to favor their aggregation and reduce the peptide solubility. In this work, we analyzed the ability to self-assemble and the gel of dipeptides based on the amino acids norvaline (Nva) and phenylalanine (Phe), studying all their combinations and not yielding to enantiomers, which display the same physicochemical properties, and hence the same self-assembly behavior in achiral environments as those studied herein. A single-crystal X-ray diffraction of all the compounds revealed fine details over their molecular packing and non-covalent interactions

Interleukin-13 induces expression and release of interleukin-1 decoy receptor in human polymorphonuclear cells.

The aim of this study was to examine whether interleukin-13 (IL-13), a cytokine with anti-inflammatory activities, affected expression of interleukin-1 (IL-1) receptors (R) in human polymorphonuclear cells (PMN). Treatment with IL-13 augmented both type I and type II (decoy) R transcripts, with the latter being by far the most represented. The transcriptional inhibitor actinomycin D blocked the induction of IL-1 R mRNAs by IL-13. Nuclear run-off experiments demonstrated an augmented transcriptional rate of IL-1 decoy R in IL-13-treated B lymphoblastoid cells. The protein synthesis inhibitor cycloheximide blocked type I R expression but superinduced decoy R expression. IL-13 augmented the binding of radiolabeled IL-1 beta on the PMN surface with an increased number of IL-1 receptors and no change in Kd values. IL-13 induced the surface expression of IL-1 decoy R and the release by PMN of an IL-1-binding protein identified as a soluble version of the IL-1 decoy R. These results show that PMN is an important target for IL-13 and that induction of expression and release of the IL-1 decoy R, in concert with inhibition of cytokine synthesis, may represent an important mechanism by which IL-13 blocks IL-1, a central mediator of inflammatory reactions

Synchrotron soft X-ray imaging and fluorescence microscopy reveal novel features of asbestos body morphology and composition in human lung tissues

Background: Occupational or environmental exposure to asbestos fibres is associated with pleural and parenchymal lung diseases. A histopathologic hallmark of exposure to asbestos is the presence in lung parenchyma of the so-called asbestos bodies. They are the final product of biomineralization processes resulting in deposition of endogenous iron and organic matter (mainly proteins) around the inhaled asbestos fibres. For shedding light on the formation mechanisms of asbestos bodies it is of fundamental importance to characterize at the same length scales not only their structural morphology and chemical composition but also to correlate them to the possible alterations in the local composition of the surrounding tissues. Here we report the first correlative morphological and chemical characterization of untreated paraffinated histological lung tissue samples with asbestos bodies by means of soft X-ray imaging and X-Ray Fluorescence (XRF) microscopy, which reveals new features in the elemental lateral distribution. Results: The X-ray absorption and phase contrast images and the simultaneously monitored XRF maps of tissue samples have revealed the location, distribution and elemental composition of asbestos bodies and associated nanometric structures. The observed specific morphology and differences in the local Si, Fe, O and Mg content provide distinct fingerprints characteristic for the core asbestos fibre and the ferruginous body. The highest Si content is found in the asbestos fibre, while the shell and ferruginous bodies are characterized by strongly increased content of Mg, Fe and O compared to the adjacent tissue. The XRF and SEM-EDX analyses of the extracted asbestos bodies confirmed an enhanced Mg deposition in the organic asbestos coating. Conclusions: The present report demonstrates the potential of the advanced synchrotron-based X-ray imaging and microspectroscopy techniques for studying the response of the lung tissue to the presence of asbestos fibres. The new results obtained by simultaneous structural and chemical analysis of tissue specimen have provided clear evidence that Mg, in addition to Fe, is also involved in the formation mechanisms of asbestos bodies. This is the first important step to further thorough investigations that will shed light on the physiopathological role of Mg in tissue response to the asbestos toxicity

Bacterial Lipopolysaccharide Rapidly Inhibits Expression of C–C Chemokine Receptors in Human Monocytes

The present study was designed to investigate the effect of bacterial lipopolysaccharide (LPS) on C–C chemokine receptors (CCR) expressed in human mononuclear phagocytes. LPS caused a rapid and drastic reduction of CCR2 mRNA levels, which binds MCP-1 and -3. CCR1 and CCR5 mRNAs were also reduced, though to a lesser extent, whereas CXCR2 was unaffected. The rate of nuclear transcription of CCR2 was not affected by LPS, whereas the mRNA half life was reduced from 1.5 h to 45 min. As expected, LPS-induced inhibition of CCR2 mRNA expression was associated with a reduction of both MCP-1 binding and chemotactic responsiveness. The capacity to inhibit CCR2 expression in monocytes was shared by other microbial agents and cytokines (inactivated Streptococci, Propionibacterium acnes, and to a lesser extent, IL-1 and TNF-α). In contrast, IL-2 augmented CCR2 expression and MCP-1 itself had no effect. These results suggest that, regulation of receptor expression in addition to agonist production is likely a crucial point in the regulation of the chemokine system

Self-Assembly of Homo- and Hetero-Chiral Cyclodipeptides into Supramolecular Polymers towards Antimicrobial Gels

There is an increasing interest towards the development of new antimicrobial coatings, especially in light of the emergence of antimicrobial resistance (AMR) towards common antibiotics. Cyclodipeptides (CDPs) or diketopiperazines (DKPs) are attractive candidates for their ability to self-assemble into supramolecular polymers and yield gel coatings that do not persist in the environment. In this work, we compare the antimicrobial cyclo(Leu-Phe) with its heterochiral analogs cyclo(D-Leu-L-Phe) and cyclo(L-Leu-D-Phe), as well as cyclo(L-Phe-D-Phe), for their ability to gel. The compounds were synthesized, purified by HPLC, and characterized by 1H-NMR, 13C-NMR, and ESI-MS. Single-crystal X-ray diffraction (XRD) revealed details of the intermolecular interactions within the supramolecular polymers. The DKPs were then tested for their cytocompatibility on fibroblast cells and for their antimicrobial activity on S. aureus. Overall, DKPs displayed good cytocompatibility and very mild antimicrobial activity, which requires improvement towards applications

Networks of superconducting nano-puddles in 1/8 doped YBa2Cu3O6.5+y controlled by thermal manipulation

While it is known that the nature and the arrangement of defects in complex oxides have an impact on the material functionalities little is known on control of superconductivity by oxygen interstitial organization in cuprates. Here we report direct compelling evidence for the control of Tc, by manipulation of the superconducting granular networks of nanoscale puddles, made of ordered oxygen stripes, in a single crystal of YBa2Cu3O6.5+y with average formal hole doping p close to 1/8. Upon thermal treatments we were able to switch from a first network of oxygen defects striped puddles with OVIII modulation (qOVIII(a*)=(h+3/8,k,0) and qOVIII(a*)=(h+5/8,k,0)), to second network characterized by OXVI modulation (qOXVI(a*)=(h+7/16,k,0) and qOXVI(a*)=(h+9/16,k,0)), and finally to a third network with puddles of OV periodicity (qOV(a*)=(4/10,1,0) and qOV(a*)=(6/10,1,0)). We map the microscopic spatial evolution of the out of plane OVIII, OXVI and OV puddles nano-size distribution via scanning micro-diffraction measurements. In particular, we calculated the number of oxygen chains (n) and the charge density (holes concentration p) inside each puddle, analyzing areas of 160x80 {\mu}m2, and recording 12800 diffraction patterns to reconstruct each spatial map. The high spatial inhomogeneity shown by all the reconstructed spatial maps reflects the intrinsic granular structure that characterizes cuprates and iron-chalcogenides, disclosing the presence of several complex networks of coexisting superconducting domains with different lattice modulations, charge density and different gaps like in the proposed multi-gaps scenario called superstripes.Comment: 5 figure

The high pressure diffraction beamline "XPRESS" at Elettra

The opening of the Xpress beamline [1] in 2016 has provided the high-pressure diffraction user community of the Elettra synchrotron facility a dedicated experimental set up at their disposal. This new beamline is part of a scientific partnership between India and Italy under a project administered through the Indian Institute of Sciences (IISc) Bangalore, for the development of a macromolecular and a high-pressure x-ray diffraction facilities, respectively XRD2 [2] and Xpress. A multipole superconducting wiggler (SCW) is the source of these two beamlines. A liquid nitrogen cooled silicon single crystal (cut along the (111) direction) hosted in the splitter chamber in the Front-End section intercepts the beam from the source (SCW) and directs it to the focusing mirror of the Xpress at a fixed energy of 25 keV. At this energy, the SCW provides a factor of 14 higher photon flux compared to the permanent magnet wiggler of XRD1, the existing diffraction beamline. The beam is focused using a toroidal mirror of 1.4 m long and 2.9 mrad grazing angle with a Pt coating to achieve 80% reflectivity at 25 keV. The focused beam from the mirror is further optimized by collimators (presently 80 micron diameter) to have intense and well defined monochromatic beam required for the high-pressure x-ray diffraction experiments. On-line pressure monitoring is achieved through a ruby fluorescence microscope connected side-by-side to the final beam collimator stage. The present experimental stage is equipped to host room temperature - high-pressure powder diffraction measurements using various kinds of Diamond Anvil Cells (DAC) in the pressure range 0-50 GPa. An image plate MAR345, with a controllable linear movement along the beam direction at two fixed vertical positions, is available for recording the diffraction pattern from both powder and single crystal samples. A Gas loading system is under commissioning, while variable temperature (300 \u2013 100 K) capillary powder diffraction stage and limited range low-temperature high-pressure measurements using a specialized DAC and liquid nitrogen cryocooler system are also planned to be added in the near future. [1] http://www.elettra.eu/elettra-beamlines/xpress.html [2] http://www.elettra.eu/elettra-beamlines/xrd2.htm

Electronic structure of MAPbI3 and MAPbCl3: importance of band alignment

Since their first appearance, organic-inorganic perovskite absorbers have been capturing the attention of the scientific community. While high efficiency devices highlight the importance of band level alignment, very little is known on the origin of the strong n-doping character observed in the perovskite. Here, by means of a highly accurate photoemission study, we shed light on the energy alignment in perovskite-based devices. Our results suggest that the interaction with the substrate may be the driver for the observed doping in the perovskite samples