Hsp100 Molecular Chaperone ClpB and Its Role in Virulence of Bacterial Pathogens

This review focuses on the molecular chaperone ClpB that belongs to the Hsp100/Clp subfamily of the AAA+ ATPases and its biological function in selected bacterial pathogens, causing a variety of human infectious diseases, including zoonoses. It has been established that ClpB disaggregates and reactivates aggregated cellular proteins. It has been postulated that ClpB’s protein disaggregation activity supports the survival of pathogenic bacteria under host-induced stresses (e.g., high temperature and oxidative stress), which allows them to rapidly adapt to the human host and establish infection. Interestingly, ClpB may also perform other functions in pathogenic bacteria, which are required for their virulence. Since ClpB is not found in human cells, this chaperone emerges as an attractive target for novel antimicrobial therapies in combating bacterial infections.     

Novel inorganic precursors [Co4.32Zn1.68(HCO2)18(C2H8N)6]/SiO2 and Co4.32Zn1.68(HCO2)18(C2H8N)6]/Al2O3 for Fischer–Tropsch synthesis

The silica- and alumina-supported Co–Zn catalysts were synthesized by thermal decomposition of new inorganic precursors [Co_4.32Zn_1.68(HCO₂)₁₈(C₂H₈N)₆]/SiO₂ or Al₂O₃. A novel coordination polymer formulated as [Co_4.32Zn_1.68(HCO₂)₁₈(C₂H₈N)₆] (1) was prepared using the solvothermal technique and characterized by elemental analysis, FT-infrared spectroscopy. Thermal stability of the complex 1 was investigated by thermogravimetric analysis and differential scanning calorimetry, and its structure was determined by single-crystal X-ray diffraction. Characterization of catalysts was carried out using powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and BET specific surface area. The catalysts were evaluated for Fischer–Tropsch synthesis (FTS) in the temperature range 200–300 °C. The results revealed that the synthesized catalysts have higher selectivity to the desired products at 260 °C. The performance of the catalysts was compared to those of catalysts constructed via impregnation method and the fabricated catalysts show higher activity and selectivity than the reference catalysts.     

Synthesis of trimethylene carbonate/ϵ‐caprolactone copolymers initiated with zinc alkoxide: influence of copolymer chain microstructure on thermal and mechanical properties

Ethylzinc(II ) ethoxide is a highly active and efficient initiator for the bulk polymerization of 1,3‐trimethylene carbonate and its copolymerization with ? ‐caprolactone. This initiator allows one to obtain (co)polymers with high molar masses in quite a short time. Significant difference in co‐monomer reactivity and relatively low participation of intermolecular transesterification processes lead to the obtained copolymers being characterized by a gradient chain microstructure. In ¹³C NMR spectra, in all regions, we observed the presence of triads which were distinctly represented by four peaks for the carbonyl signal. Mechanical tests showed that copolymers containing 70% and more of ? ‐caprolactone presented a relatively high Young's modulus and a very high maximum elongation factor; therefore these materials are promising in many biomedical applications. Due to the high reaction rate, we also made an attempt at copolymerization using reactive extrusion which gave promising results. © 2017 Society of Chemical Industry     

The pin power distribution in theVVER-1000 mock-up on the LR-0 research reactor

The pin power density distribution in reactor is an important quantity, necessary for the adequate assessment of fuel conditions and of core structures and pressure vessel radiation embrittlement as well.The paper shows the detailed comparison of calculated and experimentally determined pin by pin power distribution. To verify the reliability of measured data used for comparison with calculated data, the symmetrically located pins were measured. The calculations have been done with deterministic and Monte Carlo approach. The effect of different data libraries used for calculations are discussed as well.     

Insulating and Other Physical Properties of CoO‐Doped Zinc Oxyfluoride‐Borate Glass‐Ceramics

Zinc oxy fluoro borate glasses mixed with different concentrations of CoO (ranging from 0 to 2.0 mol%) are synthesized and subsequently crystallized. The scanning electron microscopy pictures have exhibited crystallinity. Differential scanning calorimetric studies have indicated that the prepared samples consist of multiple crystal phases. The X‐ray diffraction patterns have indicated that the glass‐ceramic samples are composed of αZn(BO₂)_2, (Zn)₃(BO₃)_2, CoF₂, CoF₃, Co₃FB₇O₁₃, ZnCo₂O₄, Co₃O₄ crystalline phases. The optical absorption and photoluminescence studies have indicated that there is a gradual increase of tetrahedral cobalt ion concentration with increase of CoO concentration in the glass network. IR spectroscopic studies have pointed out increased degree of polymerization of the zinc oxy fluoro borate glass network with increase of CoO content. The analysis of results of dielectric properties indicated increase of insulating strength of the glass‐ceramics with increase of CoO content. Finally, the dielectric breakdown strength of the samples is measured at room temperature in air medium and it is found to increase from 12.9 to 19.2 kV/cm with increase of CoO from 0.2 to 2.0 mol%. The reasons for such increase of breakdown strength are discussed quantitatively in terms of dielectric parameters with aid of data on spectroscopic properties.     

The effect of polyethylene crystallinity and polarity on thermal stability and controlled release of essential oils in antimicrobial films

Antimicrobial packaging can preserve and increase shelf life of free preservatives food products. Active materials present in the packaging material can migrate, in a controlled manner, to the food surface, avoiding bacterial and fungal proliferation and keeping the food product edible for longer periods of time. Essential oils (EO) are natural antimicrobial agents that can be released to the headspace with no direct contact between the package and the food. To minimize loses of EO during high heat melt processing, a three stages process was implemented and tested. Antimicrobial films were prepared by melt mixing a variety of polyethylene copolymers in the presence of organo‐modified montmorillonite nano clay (NC) and thymol, an EO present in oregano and thyme. A controlled EO desorption from films can be achieved by changing the polymer crystallinity and polarity. As the crystallinity increased, the thermal stability of the EO during the extrusion process improved. The addition of NC affects the structure and homogeneity of the crystals. The combination of high polymer crystallinity and chemical affinity between EO and NC increased the thermal stability of the EO during film processing, enabling to control the desorption rate. The effect of multilayer structure based on varied densities and polarities was also studied. Increasing the polarity of the outer layers in multilayered film reduced the EO desorption rate as a result of chemical interactions between the polymer and the EO. The final antimicrobial activity of the films was also found to be dependent on the EO partitioning. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40309.     

The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy

Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.     

Gaucher Disease Diagnosis Using Lyso-Gb1 on Dry Blood Spot Samples: Time to Change the Paradigm?

For years, the gold standard for diagnosing Gaucher disease (GD) has been detecting reduced β-glucocerebrosidase (GCase) activity in peripheral blood cells combined with GBA1 mutation analysis. The use of dried blood spot (DBS) specimens offers many advantages, including easy collection, the need for a small amount of blood, and simpler transportation. However, DBS has limitations for measuring GCase activity. In this paper, we recount our cross-sectional study and publish seven years of experience using DBS samples and levels of the deacylated form of glucocerebroside, glucosylsphingosine (lyso-Gb1), for GD diagnosis. Of 444 screened subjects, 99 (22.3%) were diagnosed with GD at a median (range) age of 21 (1–78) years. Lyso-Gb levels for genetically confirmed GD patients vs. subjects negative to GD diagnosis were 252 (9–1340) ng/mL and 5.4 (1.5–16) ng/mL, respectively. Patients diagnosed with GD1 and mild GBA1 variants had lower median (range) lyso-Gb1, 194 (9–1050), compared to GD1 and severe GBA1 variants, 447 (38–1340) ng/mL, and neuronopathic GD, 325 (116–1270) ng/mL (p = 0.001). Subjects with heterozygous GBA1 variants (carrier) had higher lyso-Gb1 levels, 5.8 (2.5–15.3) ng/mL, compared to wild-type GBA1, 4.9 (1.5–16), ng/mL (p = 0.001). Lyso-Gb1 levels, median (range), were 5 (2.7–10.7) in heterozygous GBA1 carriers with Parkinson’s disease (PD), similar to lyso-Gb1 levels in subjects without PD. We call for a paradigm change for the diagnosis of GD based on lyso-Gb1 measurements and confirmatory GBA1 mutation analyses in DBS. Lyso-Gb1 levels could not be used to differentiate between heterozygous GBA1 carriers and wild type.     

Existing Drugs Considered as Promising in COVID-19 Therapy

COVID-19 is a respiratory disease caused by newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease at first was identified in the city of Wuhan, China in December 2019. Being a human infectious disease, it causes high fever, cough, breathing problems. In some cases it can be fatal, especially in people with comorbidities like heart or kidney problems and diabetes. The current COVID-19 treatment is based on symptomatic therapy, so finding an appropriate drug against COVID-19 remains an immediate and crucial target for the global scientific community. Two main processes are thought to be responsible for the COVID-19 pathogenesis. In the early stages of infection, disease is determined mainly by virus replication. In the later stages of infection, by an excessive immune/inflammatory response, leading to tissue damage. Therefore, the main treatment options are antiviral and immunomodulatory/anti-inflammatory agents. Many clinical trials have been conducted concerning the use of various drugs in COVID-19 therapy, and many are still ongoing. The majority of trials examine drug reposition (repurposing), which seems to be a good and effective option. Many drugs have been repurposed in COVID-19 therapy including remdesivir, favipiravir, tocilizumab and baricitinib. The aim of this review is to highlight (based on existing and accessible clinical evidence on ongoing trials) the current and available promising drugs for COVID-19 and outline their characteristics.