Immune parameters in female workers exposed to urban pollutants

Urban outside workers, such as traffic police, are daily exposed to air pollutants and psychosocial stressors: for these workers, the working environment corresponds to the living environment of the general population. Studies in the literature have shown that immune parameters could be affected by chronic exposure to various chemical pollutants. The aim of this study is to evaluate whether occupational exposure to urban pollutants can cause alterations in NK, IL-2, IFN-gamma and C3 plasma levels in female traffic police compared to a control group. After excluding subjects with the principal confounding factors, 86 female traffic police and 87 controls were matched by age, years of police work and habitual alcohol consumption. The distribution of NK values in female traffic police and controls was significantly different (p=0.000); NK values above the upper limit of the normal laboratory range were observed in 23 female traffic police and in 2 controls (p=0.000). IL-2 mean levels were higher in traffic police compared to controls, but the difference was not significant. The mean and the distribution of IFN-gamma values in female traffic police and controls were not different. C3 mean levels were higher in female traffic police versus controls, but the difference was not significant. Considering that the subjects with the principal confounding factors were excluded from the study and that female traffic police and controls were matched by the above-mentioned variables, our results suggest that chronic occupational exposure to low doses of chemical stressors, which may interact with and add to psychosocial ones, can affect both innate and adaptative immunity.     

A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation

The M1 zinc metalloproteases ERAP1, ERAP2, and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have also been entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes, one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents, wherein the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independent of the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic micro-environment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt us to reconsider the role of ERAP2, which might have been maintained in humans due to fulfilling a relevant function in its “short” form.     

Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization,In Vitro and In Vivo Studies

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.     

Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of “onco-channelopathy”. Here, we review the contribution of ion channels and transporters in multiple myeloma (MM), a hematological neoplasia characterized by the expansion of tumor plasma cells (MM cells) in the bone marrow (BM). Deregulation of ion channels sustains MM progression by modulating intracellular pathways that promote MM cells’ survival, proliferation, and drug resistance. Finally, we focus on the promising role of ion channels as therapeutic targets for the treatment of MM patients in a combination strategy with currently used anti-MM drugs to improve their cytotoxic activity and reduce adverse effects.     

Dual Escherichia coli DNA Gyrase A and B Inhibitors with Antibacterial Activity

The emergence of multidrug-resistant bacteria is a global health threat necessitating the discovery of new antibacterials and novel strategies for fighting bacterial infections. We report first-in-class DNA gyrase B (GyrB) inhibitor/ciprofloxacin hybrids that display antibacterial activity against Escherichia coli. Whereas DNA gyrase ATPase inhibition experiments, DNA gyrase supercoiling assays, and in vitro antibacterial assays suggest binding of the hybrids to the E. coli GyrA and GyrB subunits, an interaction with the GyrA fluoroquinolone-binding site seems to be solely responsible for their antibacterial activity. Our results provide a foundation for a new concept of facilitating entry of nonpermeating GyrB inhibitors into bacteria by conjugation with ciprofloxacin, a highly permeable GyrA inhibitor. A hybrid molecule containing GyrA and GyrB inhibitor parts entering the bacterial cell would then elicit a strong antibacterial effect by inhibition of both the GyrA and GyrB subunits of DNA gyrase and potentially slow bacterial resistance development.     

Tube flow of a particulate-filled thermosetting polymer

The conservation equations of momentum, energy, and mass are numerically solved for the flow of filled thermosets reacting In a tube. The flow is assumed to be laminar and adiabatic with a constant volumetric flow rate. The critical radii are parameters that define the processability limits. The lower one is the value of the radius where an undesirable advance in the reaction extent takes place at the wall or where viscous heating leads to degradation. The upper critical radius is the radius where wall velocity is low and gelation takes place. The effects of filler volumetric fraction, wall slip velocity, and different inlet conditions are taken into account. Increasing wall slip velocity or filler fraction and decreasing inlet temperature or tube length amplify the processability zone.     

Possible mechanisms involved in apoptosis of colon tumor cell lines induced by deoxycholic acid, short-chain fatty acids, and their mixtures

OBJECTIVE: To study the effects of cryopreservation on the quality of human testicular spermatozoa and the efficiency of intracytoplasmic sperm injection (ICSI) with frozen-thawed testicular sperm into metaphase II oocytes in vitro-matured from the germinal-vesicle stage oocyte. DESIGN: Preclinical freezing study on supernumarary testicular spermatozoa after ICSI. SETTING: Tertiary IVF center coupled with an institutional research environment. PATIENT(S): Twenty-nine patients undergoing excisional testicular biopsy for ICSI. INTERVENTION(S): Isolated testicular spermatozoa were cryopreserved and thawed; frozen-thawed motile testicular spermatozoa were microinjected. MAIN OUTCOME MEASURE(S): Prefreezing and post-thawing motility and viability, survival rate, fertilization rate, cleavage rate, and embryo quality after ICSI. RESULT(S): Mean percentage motility decreased from 21% before freezing to 6% after thawing. Vitality was impaired to a similar extent, decreasing from 68% to 22% (32% recovery rate). Injection of frozen-thawed testicular spermatozoa into in vitro-matured oocytes resulted in a fertilization rate of 50.9%. Cleavage rate was severely impaired. Half of the fertilized oocytes became arrested in the one-cell stage. CONCLUSION(S): Despite the low quality of the fresh testicular spermatozoa, a high percentage of prepared testicular sperm fractions showed survival and motility after the freezing and thawing process. Injection of frozen-thawed testicular sperm into matured oocytes resulted in fertilization rates comparable with these with fresh testicular sperm, but cleavage rates were severely impaired, which might be due to source of oocytes used for ICSI.     

Rubber-modified thermosets cured in heated molds: Experimental study of phase separation profiles

An epoxy-amine thermosetting polymer, modified by 15 wt% castor oil (CO) or by a commercial rubber (epoxy-terminated butadiene-acrylonitrile copolymer, ETBN), was cured in a mold at different heating rates. CO-modified materials cured at high heating rates exhibited a nonuniform phase separation profile, i.e. a single-phase transparent core surrounded by opaque layers containing dispersed domains. The resulting structure was explained by simulating conversion vs. temperature trajectories taking place during the cure. Thermal and mechanical properties of uniform and nonuniform materials were compared. These include glass transition temperature, microhardness, yield stress and yield strain in uniaxial compression, and fracture toughness. Some possibilities for further research in this area are discussed.     

Ada Tasking: From semantics to Efficient Implementation

Tasking is one of the strengths of Ada, and, contrary to some opinion, can be implemented for a single shared processor by simple, straightforward, and efficient algorithms.