The P2Y2 Receptor C-Terminal Tail Modulates but Is Dispensable for β-Arrestin Recruitment

The P2Y₂ receptor (P2Y₂R) is a G protein-coupled receptor that is activated by extracellular ATP and UTP, to a similar extent. This allows it to play roles in the cell’s response to the (increased) release of these nucleotides, e.g., in response to stress situations, including mechanical stress and oxygen deprivation. However, despite its involvement in important (patho)physiological processes, the intracellular signaling induced by the P2Y₂R remains incompletely described. Therefore, this study implemented a NanoBiT^® functional complementation assay to shed more light on the recruitment of β-arrestins (βarr1 and βarr2) upon receptor activation. More specifically, upon determination of the optimal configuration in this assay system, the effect of different (receptor) residues/regions on βarr recruitment to the receptor in response to ATP or UTP was estimated. To this end, the linker was shortened, the C-terminal tail was truncated, and phosphorylatable residues in the third intracellular loop of the receptor were mutated, in either singly or multiply adapted constructs. The results showed that none of the introduced adaptations entirely abolished the recruitment of either βarr, although EC₅₀ values differed and time-luminescence profiles appeared to be qualitatively altered. The results hint at the C-terminal tail modulating the interaction with βarr, while not being indispensable.     

Induction of Oxidative Stress by Sunflower Phytotoxins in Germinating Mustard Seeds

The aim of this study was to investigate the phytotoxic effect of sunflower on physiological and biochemical processes during germination of mustard seeds (Sinapis alba L. cv. Nakielska). To exclude the involvement of osmotic stress in seed reaction to phytotoxic compounds, we compared the effect of 10% (w/v) water extract from sunflower (Helianthus annuus L. cv. Ogrodowy) leaves and 28.4% (w/v) polyethylene glycol (PEG) 8000 solution characterized by an equal Ψ = −1 MPa. We evaluated (1) the amount of hydrogen peroxide (H₂O₂); (2) activities of antioxidant enzymes: superoxide dismutase, catalase, and glutathione reductase; (3) membrane permeability; and (4) level of malondialdehyde (MDA). Both, sunflower compounds and PEG solutions inhibited mustard seed germination, but only phytotoxins caused an increase in the cell membrane permeability, MDA level, H₂O₂ concentration, and alterations in activities of antioxidant enzymes. Our results demonstrate that despite the activation of the antioxidant system by sunflower phytotoxins, reactive oxygen species accumulation caused cellular damage, which resulted in the decrease of germinability and gradual loss of seed vigor. It seems that the negative effect of sunflower on germination of mustard seeds is mostly because of its toxicity and not to its contribution to osmotic potential.     

Defining Dry Eye from a Clinical Perspective

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.     

Synthesis,Chiral Separation,Absolute Configuration Assignment,and Biological Activity of Enantiomers of Retro‐1 as Potent Inhibitors of Shiga Toxin

The Shiga toxin (Stx) family is composed of related protein toxins produced by the bacteria Shigella dysenteriae and certain pathogenic strains of E. coli. No effective therapies for Stx intoxication have been developed yet. However, inhibitors that act on the intracellular trafficking of these toxins may provide new options for the development of therapeutic strategies. This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of Retro‐1, a compound active against Stx and other such protein toxins. Retro‐1 works by inhibiting retrograde transport of these toxins inside cells. In vitro experiments proved that the configuration of the stereocenter at position 5 is not crucial for the activity of this compound. X‐ray diffraction data revealed (S)‐Retro‐1 to be slightly more active than (R)‐Retro‐1.     

Transparent ZnS Ceramics by Sintering of High Purity Monodisperse Nanopowders

We report an efficient way of preparing transparent ZnS ceramics using the hot‐pressing technique. It has been found that the transparency is highly dependent on the purity and the grain size distribution of the starting ZnS powders. Highly pure and monodisperse ZnS powders have been obtained by posttreatment of the precipitated powders in a H₂S/N₂ flow for 2 h at 600°C. The obtained ZnS ceramics show fully dense and homogeneous microstructure with average grain size of ~1 μm and smooth grain boundaries, leading to an excellent transmission of around 70% in the mid‐ and far‐ IR regions. The preparation technique described in this study is highly reproducible.     

The effect of aluminum alkyls and BHT‐H on reaction kinetics of silica supported metallocenes and polymer properties in slurry phase ethylene polymerization

In slurry and gas phase catalytic ethylene polymerization processes, aluminum alkyl (AlR₃) compounds are usually present inside the reactor and their role either as co‐catalyst or scavenger is of considerable importance. Silica supported metallocene/methyl aluminoxane (MAO) catalysts show specific interactions with AlR₃ compounds. Therefore, this study shows an attempt to analyze and compare the effect of concentration as well as type of commonly used AlR₃ on slurry phase ethylene homopolymerization kinetics of silica supported (n‐BuCp)₂ZrCl₂/MAO catalyst. The obtained results indicate that the lower the concentration of smaller AlR₃ compounds, the higher the instantaneous catalytic activity. Concerning the polymer particle size distributions, a rise in fines generation has been observed with increasing AlR₃ content inside the reactor. Finally, it has been shown that the addition of 2,6‐di‐tert‐butyl‐4‐methylphenol (a substituted phenol) into the reactor containing AlR₃ reduces the influence of AlR₃ compounds on the reaction kinetics of silica supported metallocene/MAO catalysts. Polyethylene properties remain similar in all the studied scenarios. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45670.     

Dielectric features of two grades of bi‐oriented isotactic polypropylene

The dielectric properties of two grades of bi‐oriented isotactic polypropylene were studied with a variety of techniques: breakdown field measurements, dielectric spectroscopy, thermally stimulated depolarization currents (Is), and direct‐current (dc) conduction I values. Standard polypropylene (STPP) and high‐crystallinity polypropylene (HCPP) films were investigated. Measurements were carried out over a wide temperature range (?150°C/+125°C). The breakdown fields in both materials showed a very small difference. On the other hand, the dielectric losses and dc conduction I values were significantly lower in HCPP. Both materials showed a decrease in the dielectric loss versus temperature in the range 20–90°C; this is favorable for application in alternating‐current power capacitors. The analysis of the dc I value allowed us to find evidence of two main conduction mechanisms: (1) below 80°C in both materials, a hopping mechanism due to the motion of electrons occurred in the amorphous phase, and (2) above 80°C, ionic conduction occurred in HCPP, and hopping conduction occurred in STPP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42224.     

Hydrodynamic characteristics of gas–solid fluidization at high temperature

Effect of temperature on the hydrodynamics of bubbling gas–solid fluidized beds was investigated in this work. Experiments were carried out at different temperatures ranged of 25–600°C and different superficial gas velocities in the range of 0.17–0.78 m/s with sand particles. The time‐position trajectory of particles was obtained by the radioactive particle tracking technique at elevated temperature. These data were used for determination of some hydrodynamic parameters (mean velocity of upward and downward‐moving particles, jump frequency, cycle frequency, and axial/radial diffusivities) which are representative to solids mixing through the bed. It was shown that solids mixing and diffusivity of particles increases by increasing temperature up to around 300°C. However, these parameters decrease by further increasing the temperature to higher than 300°C. This could be attributed to the properties of bubble and emulsion phases. Results of this study indicated that the bubbles grow up to a maximum diameter by increasing the temperature up to 300°C, after which the bubbles become smaller. The results showed that due to the wall effect, there is no significant change in the mean velocity of downward‐moving clusters. In order to explain these trends, surface tension of emulsion between the rising bubble and the emulsion phase was introduced and evaluated in the bubbling fluidized bed. The results showed that surface tension between bubble and emulsion is increased by increasing temperature up to 300°C, however, after that it acts in oppositely.     

Synthesis and Antiviral Evaluation of 3′-Fluoro-4′-modified-5′-norcarbocyclic Nucleoside Phosphonates

The synthesis and anti-HIV evaluation of hitherto unknown 3′-fluoro-5′-norcarbocyclic nucleoside phosphonates bearing adenine with modifications at the 4′ position (ethynyl, vinyl, ethyl, hydroxymethyl) is described. One of the synthesized compounds was found to be an inhibitor of HIV-1 replication, but with moderate efficiency relative to (R)-9-(2-phosphonylmethoxypropyl)adenine ((R)-PMPA, tenofovir), with no concomitant cytotoxicity.     

Comparison of Urinary Scents of Two Related Mouse Species, <Emphasis Type="Italic">Mus spicilegus</Emphasis> and <Emphasis Type="Italic">Mus domesticus</Emphasis>

Whereas the house mouse (Mus domesticus) has been studied extensively in terms of physiology/behavior and pheromonal attributes, the evolutionarily related mound-building mouse (Mus spicilegus) has received attention only recently due to its divergent behavioral traits related to olfaction. To date, no chemical studies on urinary volatile compounds have been performed on M. spicilegus. The rationale for our investigations was to determine if there are differences in urinary volatiles of intact and castrated M. spicilegus males and to explore further whether this species could utilize the same or structurally similar pheromones as the male house mouse, M. domesticus. The use of capillary gas chromatography/mass spectrometry (GC-MS) together with sorptive stir bar extraction sampling enabled quantitative comparisons between the intact and castrated M. spicilegus urinary profiles. Additionally, through GC-MS and atomic emission (sulfur-selective) detection, we identified qualitative molecular differences between intact M. spicilegus and M. domesticus. A series of volatile and odoriferous lactones and the presence of coumarin were the unique features of M. spicilegus, as was the notable absence of 2-sec-butyl-4,5-dihydrothiazole (a prominent M. domesticus male pheromone) and other sulfur-containing compounds. Castration of M. spicilegus males eliminated several substances, including δ-hexalactone and γ-octalactone, and substantially decreased additional compounds, suggesting their possible role in chemical communication. Some other M. domesticus pheromone components were also found in M. spicilegus urine. These comparative chemical analyses support the notion of metabolic similarities as well as the uniqueness of some volatiles for M. spicilegus, which may have a distinct physiological function in reproduction and behavior.