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Edible insects offer opportunities for food production, as they are an interesting source of many nutrients. In this study, the effect of pulsed electric field (PEF) and convective drying on the chemical composition with emphasizing the fat properties as well as physical, techno-functional, and thermal properties of yellow mealworm powders was investigated. The chemical composition of the yellow mealworm powders differed by PEF. When PEF was applied at 20 and 40 kJ/kg, the moisture, ash, and protein content were significantly lower, while the fat extraction yield significantly increased compared to the control sample. Furthermore, the fat extracted from these samples was characterized by a higher proportion of saturated and monounsaturated fatty acids as well as a higher thrombogenicity index, which is not beneficial from a nutritional point of view. After treatment with PEF at 5 kJ/kg, the powder was the lightest, redness and yellowness. Moreover, the highest hygroscopicity, water activity, and water and oil binding capacity for this powder were determined. The results revealed that yellow mealworm powders are a good source of macronutrients and exhibit beneficial techno-functional properties, nevertheless, the drawback is their high cohesiveness (1.27–1.44), which can be difficult to apply under industrial conditions. [ABSTRACT FROM AUTHOR]

In this work the design and development of a power processing unit for a vacuum arc thruster is presented. The thruster is part of the Seamless Radio Access Networks for Internet of Space (SeRANIS) mission of the University of the Bundeswehr Munich, which will work as first multifunctional laboratory in orbit with public access. In addition to the basic functionality of generating a voltage peak for igniting the thruster, the power processing unit is equipped with techniques for controlling the ignition sequence and monitoring desired key values. The ignition procedure starts with generating the first trigger signal up to the point where a full-blown plasma is established. The PPU guarantees reliable performance by blocking every additional incoming signal while the ignition sequence is under way and the separation of the satellite's power bus before the thruster discharges. The status of the power processing unit is constantly controlled and information is provided whether ignition was successful or not. The functionality of this circuit is based on simulation before assembly and testing. In addition, the presented system was designed to pass a test cycle of mechanical, thermal and electrical tests before being declared ready for the space mission. [ABSTRACT FROM AUTHOR]

This study was dedicated to the detailed characterization of the microstructural changes and the phase analysis of the interfaces formed in explosive welding of multilayered Ti Gr.1/A1050 clads. The significant effect of the detonation source localization on the microstructure of the welded materials interfaces after collision, and consequently on the diffusion processes induced by the elevated temperature was showed. Annealing process at 550 °C for series of time intervals of the Ti/Al clad allowed to determine the growth mechanism of the Al3Ti phase formed along particular interfaces. Moreover, the microstructure observations and calculations evidenced different growth mechanisms related to the localization of the Ti/Al interface in respect to the detonation source. [ABSTRACT FROM AUTHOR]

We numerically study the spin-wave dynamics in an antidot lattice based on a Co/Pd multilayer structure with reduced perpendicular magnetic anisotropy at the edges of the antidots. This structure forms a magnonic crystal with a periodic antidot pattern and a periodic magnetization configuration consisting of out-of-plane magnetized bulk and in-plane magnetized rims. Our results show a different behavior of spin waves in the bulk and in the rims under varying out-of-plane external magnetic field strength, revealing complex spin-wave spectra and hybridizations between the modes of these two subsystems. A particularly strong magnon–magnon coupling, due to exchange interactions, is found between the fundamental bulk spin-wave mode and the second-order radial rim modes. However, the dynamical coupling between the spin-wave modes at low frequencies, involving the first-order radial rim modes, is masked by the changes in the static magnetization at the bulk–rim interface with magnetic field changes. The study expands the horizons of magnonic-crystal research by combining periodic structural patterning and non-collinear magnetization texture to achieve strong magnon–magnon coupling, highlighting the significant role of exchange interactions in the hybridization. [ABSTRACT FROM AUTHOR]

Infectious diseases are influenced by interactions between host and pathogen, and the number of infected hosts is rarely homogenous across the landscape. Areas with elevated pathogen prevalence can maintain a high force of infection and may indicate areas with disease impacts on host populations. However, isolating the ecological processes that result in increases in infection prevalence and intensity remains a challenge. Here we elucidate the contribution of pathogen clade and host species in disease hotspots caused by Ophidiomyces ophidiicola, the pathogen responsible for snake fungal disease, in 21 species of snakes infected with multiple pathogen strains across 10 countries in Europe. We found isolated areas of disease hotspots in a landscape where infections were otherwise low. O. ophidiicola clade had important effects on transmission, and areas with multiple pathogen clades had higher host infection prevalence. Snake species further influenced infection, with most positive detections coming from species within the Natrix genus. Our results suggest that both host and pathogen identity are essential components contributing to increased pathogen prevalence. A large-scale study in Europe elucidating the contribution of pathogen clade and host species in disease hotspots caused by Ophidiomyces ophidiicola, the pathogen responsible for snake fungal disease. [ABSTRACT FROM AUTHOR]

Pure Ti (Grade 1) and Ni (type Ni201) were used to produce the Ti/Ni welds employing the explosive welding process. Thermal expansion of the welded plates was determined using dilatometric measurements from room temperature up to 600 °C. The results showed that the thermal expansion coefficient of Ti/Ni welded plates is closer to that of pure nickel than would be suggested by the Timoshenko’s model for bimetallic strip. The microstructure of the Ti/Ni interface after exposure to high temperatures revealed the presence of extensive interface porosity (Kirkendall porosity). This may cause a catastrophic disintegration of the weld during working or essential forming. The welded plates were annealed at the temperature of 650 °C under different applied compressive loads, and the applied load was shown to alter the microstructure of the NixTiy phases present at the Ti/Ni interface. Based on the obtained interface microstructural data, the strategy to suppress the Kirkendall porosity at the interface was proposed. [ABSTRACT FROM AUTHOR]

Global economic development and efforts to enhance overall quality of life yielded growth in the construction and building sector, increasing not only the demand for materials but also waste generation. Its efficient management should take full advantage of the exceptional properties of building materials. The presented work is the first reported study on possibly using waste rigid polyurethane (PUR) foam, commonly applied as thermal insulation, as particle-shaped low-density filler for manufacturing hybrid epoxy-basalt composites. It investigated the potential management of waste PUR foam by applying it as a functional filler to hybridize epoxy-basalt composites. Herein, 1, 2, 5, and 10 wt% PUR powder were introduced into the thermoset-based composites prepared using the vacuum bag method. A comprehensive analysis of mechanical and thermomechanical properties correlated with changes in the composite structure revealed the beneficial aspects of the waste filler addition associated with increased heat deflection temperature and mechanical damping ability. Introducing micrometric domains of the waste filler changed the composites' fracture character. It enabled maintaining the impact strength of composites containing up to 5 wt% of PUR powder at the level of unfilled epoxy resin. However, despite that, the incorporation of PUR powder unfavorably affected tensile and flexural performance, yielding a significant drop in moduli and strength. [ABSTRACT FROM AUTHOR]

Abstract Human papillomavirus (HPV) infection is linked to improved survival in response to chemo‐radiotherapy for patients with oropharynx head and neck squamous cell carcinoma (HNSCC). However, mechanisms involved in increased HNSCC cell death by HPV signaling in response to therapy are largely unknown. Here, using molecular, pharmacologic and genetic tools, we show that HPV early protein 7 (E7) enhances ceramide‐mediated lethal mitophagy in response to chemotherapy‐induced cellular stress in HPV‐positive HNSCC cells by selectively targeting retinoblastoma protein (RB). Inhibition of RB by HPV‐E7 relieves E2F5, which then associates with DRP1, providing a scaffolding platform for Drp1 activation and mitochondrial translocation, leading to mitochondrial fission and increased lethal mitophagy. Ectopic expression of a constitutively active mutant RB, which is not inhibited by HPV‐E7, attenuated ceramide‐dependent mitophagy and cell death in HPV(+) HNSCC cells. Moreover, mutation of E2F5 to prevent Drp1 activation inhibited mitophagy in HPV(+) cells. Activation of Drp1 with E2F5‐mimetic peptide for inducing Drp1 mitochondrial localization enhanced ceramide‐mediated mitophagy and led to tumor suppression in HPV‐negative HNSCC‐derived xenograft tumors in response to cisplatin in SCID mice.

Gastric and colorectal cancer are among the most frequently diagnosed malignancies of the gastrointestinal tract. Searching for methods of therapy that complements treatment or has a preventive effect is desirable. Bacterial metabolites safe for human health, which have postbiotic effect, are of interest recently. The study aimed to preliminary assessment of the safety, antimicrobial, and anti-cancer activity of cell-free metabolites of Gluconobacter oxydans strains isolated from Kombucha beverages as an example of the potential postbiotic activity of acetic acid bacteria (AAB). The study material consisted of five AAB strains of Kombucha origin and three human cell lines (gastric adenoma—AGS, colorectal adenoma—HT-29, and healthy cells derived from the endothelium of the human umbilical vein—HUVEC). Results of the study confirms the health safety and functional properties of selected AAB strains, including their potential postbiotic properties. The best potential anticancer activity of the AAB cell-free supernatants was demonstrated against AGS gastric adenoma cells. The conducted research proves the postbiotic potential of selected acetic acid bacteria, especially the KNS30 strain. Key points: •The beneficial and application properties of acetic acid bacteria are poorly studied. •Gluconobacter oxydans from Kombucha show a postbiotic activity. •The best anticancer activity of the G. oxydans showed against gastric adenoma. [ABSTRACT FROM AUTHOR]

Gastric and colorectal cancer are among the most frequently diagnosed malignancies of the gastrointestinal tract. Searching for methods of therapy that complements treatment or has a preventive effect is desirable. Bacterial metabolites safe for human health, which have postbiotic effect, are of interest recently. The study aimed to preliminary assessment of the safety, antimicrobial, and anti-cancer activity of cell-free metabolites of Gluconobacter oxydans strains isolated from Kombucha beverages as an example of the potential postbiotic activity of acetic acid bacteria (AAB). The study material consisted of five AAB strains of Kombucha origin and three human cell lines (gastric adenoma—AGS, colorectal adenoma—HT-29, and healthy cells derived from the endothelium of the human umbilical vein—HUVEC). Results of the study confirms the health safety and functional properties of selected AAB strains, including their potential postbiotic properties. The best potential anticancer activity of the AAB cell-free supernatants was demonstrated against AGS gastric adenoma cells. The conducted research proves the postbiotic potential of selected acetic acid bacteria, especially the KNS30 strain. Key points: •The beneficial and application properties of acetic acid bacteria are poorly studied. •Gluconobacter oxydans from Kombucha show a postbiotic activity. •The best anticancer activity of the G. oxydans showed against gastric adenoma. [ABSTRACT FROM AUTHOR]

Amyloid proteins are often associated with the onset of diseases, including Alzheimer's, Parkinson's and many others. However, there is a wide class of functional amyloids that are involved in physiological functions, e.g., formation of microbial biofilms or storage of hormones. Recent studies showed that an amyloid fibril could affect the aggregation of another protein, even from a different species. This may result in amplification or attenuation of the aggregation process. Insight into amyloid cross-interactions may be crucial for better understanding of amyloid diseases and the potential influence of microbial amyloids on human proteins. However, due to the demanding nature of the needed experiments, knowledge of such interactions is still limited. Here, we present PACT (Prediction of Amyloid Cross-interaction by Threading) - the computational method for the prediction of amyloid cross-interactions. The method is based on modeling of a heterogeneous fibril formed by two amyloidogenic peptides. The resulting structure is assessed by the structural statistical potential that approximates its plausibility and energetic stability. PACT was developed and first evaluated mostly on data collected in the AmyloGraph database of interacting amyloids and achieved high values of Area Under ROC (AUC=0.88) and F1 (0.82). Then, we applied our method to study the interactions of CsgA - a bacterial biofilm protein that was not used in our in-reference datasets, which is expressed in several bacterial species that inhabit the human intestines - with two human proteins. The study included alpha-synuclein, a human protein that is involved in Parkinson's disease, and human islet amyloid polypeptide (hIAPP), which is involved in type 2 diabetes. In both cases, PACT predicted the appearance of cross-interactions. Importantly, the method indicated specific regions of the proteins, which were shown to play a central role in both interactions. We experimentally confirmed the novel results of the indicated CsgA fragments interacting with hIAPP based on the kinetic characteristics obtained with the ThT assay. PACT opens the possibility of high-throughput studies of amyloid interactions. Importantly, it can work with fairly long protein fragments, and as a purely physicochemical approach, it relies very little on scarce training data. The tool is available as a web server at https://pact.e-science.pl/pact/. The local version can be downloaded from https://github.com/KubaWojciechowski/PACT. [ABSTRACT FROM AUTHOR]

Abstract Mechanisms that alter protein phosphatase 2A (PP2A)‐dependent lung tumour suppression via the I2PP2A/SET oncoprotein are unknown. We show here that the tumour suppressor ceramide binds I2PP2A/SET selectively in the nucleus and including its K209 and Y122 residues as determined by molecular modelling/simulations and site‐directed mutagenesis. Because I2PP2A/SET was found overexpressed, whereas ceramide was downregulated in lung tumours, a sphingolipid analogue drug, FTY720, was identified to mimick ceramide for binding and targeting I2PP2A/SET, leading to PP2A reactivation, lung cancer cell death, and tumour suppression in vivo. Accordingly, while molecular targeting of I2PP2A/SET by stable knockdown prevented further tumour suppression by FTY720, reconstitution of WT‐I2PP2A/SET expression restored this process. Mechanistically, targeting I2PP2A/SET by FTY720 mediated PP2A/RIPK1‐dependent programmed necrosis (necroptosis), but not by apoptosis. The RIPK1 inhibitor necrostatin and knockdown or genetic loss of RIPK1 prevented growth inhibition by FTY720. Expression of WT‐ or death‐domain‐deleted (DDD)‐RIPK1, but not the kinase‐domain‐deleted (KDD)‐RIPK1, restored FTY720‐mediated necroptosis in RIPK1−/− MEFs. Thus, these data suggest that targeting I2PP2A/SET by FTY720 suppresses lung tumour growth, at least in part, via PP2A activation and necroptosis mediated by the kinase domain of RIPK1.

To evaluate the prevalence of probable, confirmed, and severe sarcopenia in spondyloarthritis (SpA), according to the European Working Group on Sarcopenia in Older People 2019 (EWGSOP2) definition. A total of 103 patients (51% women) with SpA, mean age 47.1 ± 13.7 years, were included and compared to 103 age- and sex-matched controls. Grip strength was measured by dynamometry. Body composition was assessed by whole-body densitometry. In SpA patients gait speed was measured by the 4-m-distance walk test and quality of life was evaluated with a specific health-related questionnaire for sarcopenia (SaRQoL®). Twenty-two SpA patients (21%) versus 7 controls (7%) had a low grip strength, i.e., probable sarcopenia (p < 0.01), 15 SpA (15%) patients and 7 controls (7%) had low Skeletal Muscle mass Index (SMI) (ns), respectively, and 5 and 2% of SpA patients and controls had low grip strength and low SMI, i.e., confirmed sarcopenia (ns). All the sarcopenic SpA patients had a low gait speed, i.e., severe sarcopenia. Finally, probable sarcopenic SpA patients had significantly higher C-Reactive Protein (CRP, p < 0.001) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI score, p < 0.01), lower gait speed (p < 0.001), and SarQoL® score (p < 0.001) than SpA patients with normal grip strength. According to EWGSOP2 definition, the prevalence of probable sarcopenia was significantly higher in SpA patients compared to controls. Probable sarcopenia was associated with higher inflammation and disease activity, impaired muscle performance, and quality of life. These results suggest that muscle strength may be a salient hallmark in SpA. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) affects human health worldwide as a high-risk disease. It can neither be easily controlled by current vaccines and nor be treated by conventional drugs. Gemini surfactants (GS) have shown several properties including antiviral activity. In this study, the antiviral capacity of some GS compounds with different levels of hydrophobicity was examined. The 50% cytotoxic (CC50) and non-cytotoxic (NCTC) concentrations of the compounds were determined by MTT method. The NCTCs, the same as effective concentrations (EC50s), were tested for the antiviral capacity against IAV in different combination treatments for 1 h incubation on MDCK cells. The HA and MTT assays were used to evaluate the virus titer and cell viabilities, respectively. The hemolytic activity of the compounds was also assessed using an HA inhibition assay. To evaluate the apoptotic effect of GS compounds, Annexin V-PI kit was used. The HA titers decreased between 1–6.5 logs, 1–4.5 logs, and 1–5.5 logs in simultaneous, pre- and post-penetration combination treatments, respectively. The cell viability values in all combination treatments were favorable. The HI assay indicated the hemolytic potential of GSs and their physical interaction with viral HA. The apoptosis test results highlighted anti-apoptotic capacity of the GS compounds alone and in the presence of influenza virus especially for the hydrophobic ones. Gemini surfactants were generally more efficacious in simultaneous treatment. Their antiviral potential may be attributed to their physical interaction with viral membrane or HA glycoprotein that disrupts viral particle or blocks viral entry to the cell and inhibits its propagation. [ABSTRACT FROM AUTHOR]

Summary: In older men, higher high-sensitivity C-reactive protein (hsCRP) concentrations were associated with faster prospectively assessed endocortical expansion (distal radius, distal tibia) and slightly higher cortical bone loss at distal tibia, but not with the fracture risk. High hsCRP level has a limited impact on bone decline in older men. Purpose: Data on the link of the high-sensitivity C-reactive protein (hsCRP) with bone loss and fracture risk are discordant. We studied the association of the hsCRP with the prospectively assessed decrease in areal bone mineral density (aBMD), bone microarchitecture decline, and fracture risk in older men. Methods: At baseline, hsCRP was measured in 823 men aged 60–88. Areal BMD and bone microarchitecture (distal radius, distal tibia) were assessed by dual-energy X-ray absorptiometry and high-resolution peripheral QCT, respectively, at baseline and after 4 and 8 years. Data on incident fractures were collected for 8 years. Results: Higher hsCRP concentration was associated with faster increase in aBMD at the whole body and lumbar spine, but not other sites. Higher hsCRP levels were associated with faster decrease in cortical area and more rapid increase in trabecular area at the distal radius (0.048 mm2/year/SD, p < 0.05) and distal tibia (0.123 mm2/year/SD, p < 0.001). At the distal tibia, high hsCRP level was associated with greater decrease in total and cortical volumetric BMD (vBMD) and in failure load. The hsCRP levels were not associated with the fracture risk, even after accounting for competing risk of death. Conclusion: Higher hsCRP levels were associated with greater endocortical expansion at the distal radius and tibia. Higher hsCRP was associated with slightly faster decrease in total and cortical vBMD and failure load at distal tibia, but not with the fracture risk. Thus, high hsCRP levels are associated with faster cortical bone loss, but not with fracture risk in older men. [ABSTRACT FROM AUTHOR]

The INTENSE project, supported by the EU Era-Net Facce Surplus, aimed at increasing crop production on marginal land, including those with contaminated soils. A field trial was set up at a former wood preservation site to phytomanage a Cu/PAH-contaminated sandy soil. The novelty was to assess the influence of five organic amendments differing in their composition and production process, i.e. solid fractions before and after biodigestion of pig manure, compost and compost pellets (produced from spent mushroom substrate, biogas digestate and straw), and greenwaste compost, on Cu availability, soil properties, nutrient supply, and plant growth. Organic amendments were incorporated into the soil at 2.3% and 5% soil w/w. Total soil Cu varied from 179 to 1520 mg kg−1, and 1 M NH4NO3-extractable soil Cu ranged from 4.7 to 104 mg kg−1 across the 25 plots. Spring barley (Hordeum vulgare cv. Ella) was cultivated in plots. Changes in physico-chemical soil properties, shoot DW yield, shoot ionome, and shoot Cu uptake depending on extractable soil Cu and the soil treatments are reported. Shoot Cu concentration varied from 45 ± 24 to 140 ± 193 mg kg DW−1 and generally increased with extractable soil Cu. Shoot DW yield, shoot Cu concentration, and shoot Cu uptake of barley plants did not significantly differ across the soil treatments in year 1. Based on soil and plant parameters, the effects of the compost and pig manure treatments were globally discriminated from those of the untreated, greenwaste compost and digested pig manure treatments. Compost and its pellets at the 5% addition rate promoted soil functions related to primary production, water purification, and soil fertility, and the soil quality index. [ABSTRACT FROM AUTHOR]

This study is dedicated to the Cu/P265GH steel interface zone produced by explosive welding subjected to stress relief annealing followed by the complex microstructure characterization. The analysis was carried out with aim of the variety of scanning and transmission electron microscopy techniques. Presented characteristics showed that the interface zone was continuous and of wavy morphology with locally visible melted zones under the wave vortices consisting of the joined materials. On the other hand, chemical compositions changes across the apparently sharp interface (metal/metal bond) in-between the waves showed copper-iron diffusion across the bonding interface. High-magnification observations of this interface confirmed the formation of a thin nanocrystalline interlayer of about 150 nm in thickness, composed of Cu and Fe mixed grains. Electron backscattered diffraction analysis evidenced the presence of annealing twins within the copper grains and also slight texturing of the copper grains toward <111>, being perpendicular to the plane of the weld. Moreover, for the first time, dilatometric measurements of Cu/P265GH steel clads were performed in the temperature range of 25–600 °C, revealing that the thermal expansion values were within the range of the reference materials—copper and steel. These preliminary studies showed that the obtained thermal expansion values of the investigated platers were exactly between the values for the reference materials Cu and P265GH steel. [ABSTRACT FROM AUTHOR]

This study presents a detailed analysis of the interface zone microstructure formed during explosive welding of aluminum alloy A1050 with S355J2N steel. The A1050 flyer plate was shot onto the base material carbon steel plate of improved strength and weldability. Aluminum alloy is characterized by very good resistance to atmospheric corrosion and high thermal and heat conductivity. Therefore, their combination brings about very good mechanical properties, especially high strength as well as improved corrosion resistance, which makes these materials potential candidates as an anode for active electrochemical corrosion protection applications. To characterize the microstructure of the welds, the observations were carried out by means of scanning and transmission electron microscopy techniques. Investigations performed on the cross sections allowed to study the interface morphology, as well as the microstructural changes of the joined materials in the vicinity of the bonding zone both at the micro- and nanoscale. The analysis of the results presented in the paper shows that within the wavy interface characteristic zones can be identified-melted regions and apparently sharp interface. The examined complex microstructures were composed of solid solutions, intermetallic phases, and quasicrystals. Moreover, for the first time, the thermal expansion measurements of A1050/S355J2N explosively welded platers were carried out. [ABSTRACT FROM AUTHOR]

This study presents the microstructure and physicochemical properties of explosively welded Inconel 625 and Ti6Al4V platers, which were investigated by scanning electron microscopy, corrosion resistance, and dilatometric measurements. Firstly, the corrosion behavior of Ti6Al4V was tested in sodium sulfate and sodium chloride solutions using potentiodynamic polarization and electrochemical impedance spectroscopy techniques. The experimental results were compared with the data obtained from computer simulation. The investigated corrosion resistance of the explosively welded Inconel 625/Ti6Al4V system in different solutions showed that this system exhibited significantly higher corrosion resistance in NaCl solution than in sodium sulfate. In addition, the corrosion potential of the Ti6Al4V surface tested in sodium chloride is slightly higher compared to the value obtained for the second solution. Moreover, the pioneering dilatometric measurements have been carried out in the temperature range of 298-873 K to determine the linear coefficient values of thermal expansion (α) of investigated samples cut along and perpendicular to the direction of the explosion. They showed close values regardless of the cutting direction. Additionally, α possessed the linear character in the whole investigated temperature range, excluding the phase transitions within the bonded plates. [ABSTRACT FROM AUTHOR]

CHIP (C‐terminus of Hsc70‐interacting protein) and its worm ortholog CHN‐1 are E3 ubiquitin ligases that link the chaperone system with the ubiquitin‐proteasome system (UPS). CHN‐1 can cooperate with UFD‐2, another E3 ligase, to accelerate ubiquitin chain formation; however, the basis for the high processivity of this E3s set has remained obscure. Here, we studied the molecular mechanism and function of the CHN‐1–UFD‐2 complex in Caenorhabditis elegans. Our data show that UFD‐2 binding promotes the cooperation between CHN‐1 and ubiquitin‐conjugating E2 enzymes by stabilizing the CHN‐1 U‐box dimer. However, HSP70/HSP‐1 chaperone outcompetes UFD‐2 for CHN‐1 binding, thereby promoting a shift to the autoinhibited CHN‐1 state by acting on a conserved residue in its U‐box domain. The interaction with UFD‐2 enables CHN‐1 to efficiently ubiquitylate and regulate S‐adenosylhomocysteinase (AHCY‐1), a key enzyme in the S‐adenosylmethionine (SAM) regeneration cycle, which is essential for SAM‐dependent methylation. Our results define the molecular mechanism underlying the synergistic cooperation of CHN‐1 and UFD‐2 in substrate ubiquitylation. Synopsis: The regulation of CHIP quality control ubiquitin ligase activity and its substrate selectivity is largely unclear. Here, biochemical, computational, proteomic, and lipidomic data unravel the regulatory mechanism of CHIP processivity, and reveal its role in lipid metabolism. The E3 ligase UFD‐2 stimulates the ubiquitylation activity of CHIP/CHN‐1UFD‐2 binding promotes dimerization of the CHIP/CHN‐1 U‐box domains and E2 enzyme discharging capacityHSP70/HSP‐1, by latching the U‐box and TPR domains, stabilizes the autoinhibitory state of CHIP/CHN‐1, thus limiting its interactions with E2s and UFD‐2Assembly with UFD‐2 enables CHIP/CHN‐1 to regulate lipid metabolism via S‐adenosylhomocysteinase (AHCY‐1) ubiquitylation [ABSTRACT FROM AUTHOR]

Klinefelter Syndrome (KS) patients, defined by a 47 XXY karyotype, have increased risk of fragility fractures. We have assessed bone microarchitecture by high resolution peripheral quantitative CT (HR-pQCT) at the radius and tibia in young KS patients, naïve from testosterone replacement therapy (TRT). Areal bone mineral density (BMD) and body composition were assessed by dual X-ray absorptiometry (DXA). Total testosterone (tT) was measured at baseline. Bone measurements have been repeated after 30 months of TRT. We enrolled 24 KS patients and 72 age-matched controls. KS patients were (mean ± SD) 23.7 ± 7.8 year-old. KS patients had significantly lower relative appendicular lean mass index (RALM) and lower aBMD at spine and hip than controls. Ten patients (42%) had low tT level (≤ 10.4 nmol/L). At baseline, we observed at radius a marked cortical (Ct) impairment reflected by lower Ct.area, Ct.perimeter, and Ct.vBMD than controls. At tibia, in addition to cortical fragility, we also found significant alterations of trabecular (Tb) compartment with lower trabecular bone volume (BV/TV) and Tb.vBMD as compared to controls. After 30 months of TRT, 18 (75%) KS patients were reassessed. Spine aBMD and RALM significantly increased. At radius, both cortical (Ct.Pm, Ct.Ar, Ct.vBMD, Ct.Th) and trabecular (Tb.vBMD) parameters significantly improved. At tibia, the improvement was found only in the cortical compartment. Young TRT naïve KS patients have inadequate bone microarchitecture at both the radius and tibia, which can improve on TRT. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is a type of diet in which the intake of fats significantly increases at the cost of carbohydrates while maintaining an adequate amount of proteins. This kind of diet has been successfully used in clinical therapies of drug-resistant epilepsy, but there is still insufficient evidence on its safety when used in pregnancy. To assess KD effects on the course of gestation and fetal development, pregnant females were fed with: (i) KD during pregnancy and lactation periods (KD group), (ii) KD during pregnancy replaced with ND from the day 2 postpartum (KDND group) and (iii) normal diet alone (ND group). The body mass, ketone and glucose blood levels, and food intake were monitored. In brains of KD-fed females, FTIR biochemical analyses revealed increased concentrations of lipids and ketone groups containing molecules. In offspring of these females, significant reduction of the body mass and delays in neurological development were detected. However, replacement of KD with ND in these females at the beginning of lactation period led to regainment of the body mass in their pups as early as on the postnatal day 14. Moreover, the vast majority of our neurological tests detected functional recovery up to the normal level. It could be concluded that the ketogenic diet undoubtedly affects the brain of pregnant females and impairs the somatic and neurological development of their offspring. However, early postnatal withdrawal of this diet may initiate compensatory processes and considerable functional restitution of the nervous system based on still unrecognized mechanisms. [ABSTRACT FROM AUTHOR]

Risk factors of physical performance decline in older men remain uncertain. We assessed risk factors of incident physical performance deterioration in older men followed up prospectively. In a cohort of 821 men aged 60–87, physical performance was assessed by four tests (five chair stands, standing with closed eyes, forward and backward tandem walk) at baseline, 4 and 8 years. Various predictive biological measurements were performed at baseline. Serum creatinine/ cystatin C (Cr/CysC) ratio was used as an index of muscle mass. In multivariate models, higher age, higher fat mass index (FMI = fat mass/height2), low physical activity, prior stroke and fracture were associated with poor physical performance at baseline. Higher age, low physical activity, low calcium intake, prior non-vertebral fractures, low apparent free testosterone concentration and poor health status were associated with higher risk of loss to follow-up. Low grip strength, Parkinson's disease and stroke were associated with higher risk of incident inability to do five chair stands. Low Cr/CysC ratio and high FMI were associated with high risk of incident inability to perform forward and backward tandem walk. Sarcopenic obesity (co-occurrence of lower tertile of Cr/CysC and upper tertile of FMI) was associated with higher risk of incident inability to perform forward (OR = 3.31, 95% CI 1.88–5.84, p < 0.001) and backward tandem walk and of incident inability to perform more than one test (OR = 5.82, 95% CI 1.29–26.27, p < 0.001). In conclusion, sarcopenic obesity and poor health are associated with higher risk of incident severe decline of physical performance. [ABSTRACT FROM AUTHOR]

Introduction : Recent technological advances with dual-energy quantitative computed tomography (DEQCT) allow to combine two images of different level of energy to obtain simulated mono-energetic images at 60 keV (SIM60KeV-QCT) with improved image contrast in clinical practice. This study includes three topics: (1) compare bone mineral content (BMC), areal and volumetric bone mineral density (aBMD, vBMD) obtained with SIM60KeV-QCT, single-energy QCT (SEQCT), and dual X-ray absorptiometry (DXA); (2) compare ash density and weight with respective vBMD and BMC assessed on SIM60KeV-QCT, SEQCT, and DXA; and (3) compare the influence of reconstruction kernels on the accuracy of vBMD and BMC using ash density and ash weight as the reference values. Methods: DXA, SEQCT, and DEQCT acquisitions were performed ex vivo on 42 human femurs. Standard kernel (SK) and bone kernel (BK) were applied to each stack of images. Ten diaphyses and 10 femoral necks were cut, scanned, and reconstructed using the techniques described above. Finally, the bone specimens were calcined to obtain the ash weight. Results: QCT analysis (SEQCT, SIM60KeV-QCT) underestimated BMC value compared to DXA. For femoral necks, all QCT analyses provided an unbiased estimate of ash weight but underestimated ash density regardless of the kernel used. For femoral diaphysis, SEQCT BK, SIM60KeV-QCT BK, and SK underestimated ash weight but not ash density. Conclusion: BMC and vBMD quantifications with the SIM60KeV-QCT gave similar results as the SEQCT. Further studies are needed to optimize the use of SIM60KeV-QCT in clinical situations. SK should be used given the effect of kernels on QCT assessment. [ABSTRACT FROM AUTHOR]

Ubiquitin ligases control the degradation of core clock proteins to govern the speed and resetting properties of the circadian pacemaker. However, few studies have addressed their potential to regulate other cellular events within clock neurons beyond clock protein turnover. Here, we report that the ubiquitin ligase, UBR4/POE, strengthens the central pacemaker by facilitating neuropeptide trafficking in clock neurons and promoting network synchrony. Ubr4-deficient mice are resistant to jetlag, whereas poe knockdown flies are prone to arrhythmicity, behaviors reflective of the reduced axonal trafficking of circadian neuropeptides. At the cellular level, Ubr4 ablation impairs the export of secreted proteins from the Golgi apparatus by reducing the expression of Coronin 7, which is required for budding of Golgi-derived transport vesicles. In summary, UBR4/POE fulfills a conserved and unexpected role in the vesicular trafficking of neuropeptides, a function that has important implications for circadian clock synchrony and circuit-level signal processing. Although ubiquitin ligases are known to control clock protein degradation, their other roles in clock neurons are unclear. Here the authors report that UBR4 promotes export of neuropeptides from the Golgi for axonal trafficking, which is important for circadian clock synchrony in mice and flies. [ABSTRACT FROM AUTHOR]

The present paper discusses the impact of land use and seasons on the concentration of nutrients in the waters of the Utrata River (Pruszków Poviat, Mazowieckie Voivodeship) from April 2018 to March 2019. The pollution of rivers by nutrients is a major problem for society. Surface water is a source of drinking water, water used for industrial and agricultural purposes. With the increasing pollution of rivers, the purification process for these purposes becomes more expensive and more challenging. To assist in carrying out activities aimed at reducing the inflow of biogenic substances into large river systems and then down to the Baltic Sea, we analyzed the spatial and temporal dynamics of loads from the entire Utrata River catchment area. We divided the entire catchment area into three impact zones: grasslands and wastelands, urbanized areas, and agricultural land and examined changes in nutrient concentrations (total phosphorus, nitrate nitrogen, ammonium nitrogen) in each of the zones. The results were statistically processed using the 1-factor ANOVA method with the p-value of significance below 0.05. Research indicates an increase in the concentration of total phosphorus and nitrogen forms down the course of the river in urban and agricultural areas with persistently low concentrations of these biogenic substances in grasslands. [ABSTRACT FROM AUTHOR]

Objectives: Assessment of the progression of abdominal aortic calcification (AAC) may be a surrogate marker of the impact of physical function on cardiovascular risk. Our aim was to assess the risk of rapid AAC progression in older men with low relative appendicular lean mass (RALM) and poor physical function. Design: Prospective cohort study. Setting: Community-dwelling older men. Participants: 621 men aged 50–85 followed prospectively (baseline, 3 and 7.5 years). Measurements: Body composition was assessed by DXA. Poor physical function was defined as incapacity to perform ≥1 of 5 clinical tests (balance, muscle strength). AAC was assessed using Kauppila's semiquantitative score. Reclassification improvement was assessed by comparing the areas under the curve (AUC) using DeLong's method. Results: Rapid AAC progression (>0.6 point/year) was found in 168 men (27.1%). After adjustment for confounders including baseline AAC, the risk of rapid AAC progression increased with lower RALM (OR=1.42/SD, 95%CI: 1.09–1.86, p<0.01) and was higher in the lowest (<7.5kg/m2) vs. highest (>8.6kg/m2) quartile (OR=2.15, 95%CI: 1.17–3.95, p<0.01). Poor physical performance was associated with rapid AAC progression (OR=2.76, 95%CI: 1.48–5.91, p<0.005). Low RALM (<7.84kg/m2 defined using Youden's index) and poor physical function contributed to the risk of rapid AAC progression jointly. Men who had low RALM and poor physical function had higher risk of rapid AAC progression vs. men without these traits (OR=4.66, 95%CI: 1.72–12.62, p<0.05). RALM and physical function improved the identification of men with rapid AAC progression (AAUC=0.026, 95%CI: 0.005–0.046, p<0.05) after adjustment for confounders including baseline AAC score. Conclusions: Low RALM and poor physical function are associated with higher risk of rapid AAC progression and possibly represent another measure of cardiovascular risk. [ABSTRACT FROM AUTHOR]

In this paper, the authors propose, investigate, and discuss a concept of novel type of deployable helium-filled aerostat as a low-cost mean of transport. Internal construction of the aerostat is based on ultra-light tensegrity structure equipped with prestressed tensioned elements of controllable lengths. Such tensegrity structure allows for adaptive morphing of the aerostat understood as simultaneous controllable modifications of aerostat volume and shape during the flight. The controlled volume changes enable influencing buoyancy force and obtaining desired vertical motion during the ascending and descending process. In turn, external shape changes allow for lowering the aerodynamic drag and energy usage needed to uphold stable horizontal position or maintain the desired flight path. Moreover, such internal structure allows for convenient storage, transportation and deployment of the aerostat construction on the ground or in required point at the atmosphere. The article presents an analysis of the exemplary operational mission of the aerostat. The authors introduce the mechanical model capturing interaction of the internal tensegrity structure and aerostat envelope based on the finite-element method, as well as dynamic model allowing for simulation of the aerostat's vertical and horizontal motion influenced by buoyancy and drag forces. Both these models are used to positively verify the feasibility of the proposed concept of deployable tensegrity-based aerostat with adaptive morphing and its efficiency in realization of the assumed flight mission. [ABSTRACT FROM AUTHOR]

High-resolution peripheral computed tomography (HR-pQCT) was developed to image bone microarchitecture in vivo at peripheral skeletal sites. Since the introduction of HR-pQCT in 2005, clinical research to gain insight into pathophysiology of skeletal fragility and to improve prediction of fractures has grown. Meanwhile, the second-generation HR-pQCT device has been introduced, allowing novel applications such as hand joint imaging, assessment of subchondral bone and cartilage thickness in the knee, and distal radius fracture healing. This article provides an overview of the current clinical applications and guidance on interpretation of results, as well as future directions. Specifically, we provide an overview of (1) the differences and reference data for HR-pQCT variables by age, sex, and race/ethnicity; (2) fracture risk prediction using HR-pQCT; (3) the ability to monitor response of anti-osteoporosis therapy with HR-pQCT; (4) the use of HR-pQCT in patients with metabolic bone disorders and diseases leading to secondary osteoporosis; and (5) novel applications of HR-pQCT imaging. Finally, we summarize the status of the application of HR-pQCT in clinical practice and discuss future directions. From the clinical perspective, there are both challenges and opportunities for more widespread use of HR-pQCT. Assessment of bone microarchitecture by HR-pQCT improves fracture prediction in mostly normal or osteopenic elderly subjects beyond DXA of the hip, but the added value is marginal. The prospects of HR-pQCT in clinical practice need further study with respect to medication effects, metabolic bone disorders, rare bone diseases, and other applications such as hand joint imaging and fracture healing. The mostly unexplored potential may be the differentiation of patients with only moderately low BMD but severe microstructural deterioration, which would have important implications for the decision on therapeutical interventions. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "A heterotypic assembly mechanism regulates CHIP E3 ligase activity" published in the EMBO Journal. The authors contacted the journal to inform them of errors in the graphical abstract, results section, and figure legend of Figure 5A. The corrections have been made to the graphical abstract, results section, and figure legend. These changes do not impact the text or conclusions of the article. The authors of the article are listed at the end of the correction notice. [Extracted from the article]

This work presents a detailed description of a bonding zone of explosively welded Ti/steel clads subjected to stress relief annealing, applied in order to improve the plasticity of the final product. The typical joint formed by the welding process possesses a characteristic wavy interface with melted regions observed mainly at the crest regions of waves. The interface of Ti/steel clads before and after annealing was previously investigated mostly in respect to the melted regions. Here, a sharp interface between the waves was analyzed in detail. The obtained results indicate that the microstructure of a transition zone of that area is different along the width. After the heat treatment at 600 °C for 1.5 hours, titanium carbide (TiC) together with α-Fe phase forms at the interface in local areas of relatively wide interlayer (~ 1 µm), while for most of the sharp interface, a much thinner zone up to about 400 nm, formed by four sublayers containing intermetallic phase and carbides, is present. This confirms that carbon diffusion induced by applied heat treatment significantly influences the final microstructure of the Ti/steel interface zone. Side bending tests confirmed high plasticity of welds after applied heat treatment; however, the microhardness measurements indicated that the strengthening of the steel in the vicinity of the interface had not been removed completely. [ABSTRACT FROM AUTHOR]

Several disorders are related to amyloid aggregation of proteins, for example Alzheimer's or Parkinson's diseases. Amyloid proteins form fibrils of aggregated beta structures. This is preceded by formation of oligomers—the most cytotoxic species. Determining amyloidogenicity is tedious and costly. The most reliable identification of amyloids is obtained with high resolution microscopies, such as electron microscopy or atomic force microscopy (AFM). More frequently, less expensive and faster methods are used, especially infrared (IR) spectroscopy or Thioflavin T staining. Different experimental methods are not always concurrent, especially when amyloid peptides do not readily form fibrils but oligomers. This may lead to peptide misclassification and mislabeling. Several bioinformatics methods have been proposed for in-silico identification of amyloids, many of them based on machine learning. The effectiveness of these methods heavily depends on accurate annotation of the reference training data obtained from in-vitro experiments. We study how robust are bioinformatics methods to weak supervision, encountering imperfect training data. AmyloGram and three other amyloid predictors were applied. The results proved that a certain degree of misannotation in the reference data can be eliminated by the bioinformatics tools, even if they belonged to their training set. The computational results are supported by new experiments with IR and AFM methods. [ABSTRACT FROM AUTHOR]

10-Alkylthiocolchicines have been obtained and characterized by spectroscopic methods and their biological activities as: cytotoxic, anti-inflammatory and analgesic activities have been tested. Cytotoxic activity against SKOV-3 ovarian cell line for 10-alkylthiocolchicine analogues was reported and tested compounds showed to be more active than commonly used doxorubicin. Some of tested C-10 alkylthiolated colchicines have been found to exhibit cytotoxicity at levels comparable to that of the natural product—colchicine. 10-Methylthiocolchicine has IC50 = 8 nM and 10-ethylthiocolchicine has IC50 = 47 nM in comparison to colchicine IC50 = 37 nM. Moreover for 10-alkylthioderivatives apoptosis test, cyclin B1 and cell cycle tests were performed. 10-n-Butylthiocolchicine was tested for anti-inflammatory and analgesic activities it showed to produce analgesic rather than anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

The paper presents the effects of the dam reservoir in Komorów on the water quality in the Utrata river. The implementation of the adopted objective involved a comparison of water quality at two points, above and below the reservoir. The Utrata River is polluted with biogenic compounds throughout the whole section studied. COD content also indicates significant contamination exceeding permissible limits. A positive effect of the reservoir on water quality in the river was also observed in terms of the content of dissolved oxygen, with concentration increasing below the reservoir. The reservoir had a positive effect on reducing the concentration of total phosphorus in the water. Water in the Utrata below the reservoir showed higher values of chemical oxygen demand (CODMn) than above the reservoir. There were no differences in the concentration of NH4+ and NO3- ions in the water before and after the reservoir. [ABSTRACT FROM AUTHOR]

This study presents an analysis of the structure and properties of different types of lignocellulosic fillers modified by isophorone diisocyanate (IPDI) to provide insights into the possibility of their application to the manufacturing of wood polymer composites (WPCs). Moreover, it deals with the environmental aspects of modified fillers, by assessment of volatile organic compounds (VOCs) emitted during modification, as well as from final products. Three types of commercially available lignocellulosic fillers were modified with different content of IPDI (from 1 to 15 wt%) using the internal mixer. The main compounds detected in the air during modifications were terpenes and terpenoids. No IPDI was detected, which is very beneficial considering its toxicity. On the other hand, IPDI was emitted from modified fillers at a slightly elevated temperature of 40 °C, which was associated with a significant rise in its vapor pressure. Successful modification of fillers was confirmed by FTIR spectroscopy and thermogravimetric analysis. Performed modifications of lignocellulosic fillers with IPDI had a relatively small impact on their particle size and color properties. Such an effect can be considered beneficial for the mechanical performance and appearance of WPCs, which could be potentially manufactured using IPDI-modified lignocellulosic fillers. [ABSTRACT FROM AUTHOR]

Purpose of Review: Low muscle strength and poor physical performance are associated with high risk of fracture. Many studies assessed clinical and functional outcomes of fractures. Fewer studies analyzed the impact of fractures on muscle strength and physical performance. Recent Findings: Vertebral fractures (especially multiple and severe ones) are associated with back pain, back-related disability, lower grip strength, lower strength of lower limbs, lower gait speed, and poor balance. Patients with hip fracture have slower gait and lower quadriceps strength. Non-vertebral fractures were associated with lower strength of the muscles adjacent to the fracture site (e.g., grip strength in the case of distal radius fracture, knee extensors in the case of patellar fracture) and poor physical function dependent on the muscles adjacent to the fracture site (e.g., limited range of motion of the shoulder in the case of humerus fracture, gait disturbances in the case of the ankle fracture). Individuals with a fracture experience a substantial deterioration of muscle strength and physical performance which exceeds that related to aging and is focused on the period close to the fracture occurrence. After fracture, muscle strength increased and physical performance improved. The rate of normalization depended partly on the therapeutic approach and on the rehabilitation program. A subgroup of patients, mainly the elderly, never returns to the pre-fracture level of physical performance. Summary: The permanent decline of physical function after fracture may be related to the limitation of movements due to pain, low physical activity, poor health before the fracture, and reduced efficacy of retraining after immobilization. [ABSTRACT FROM AUTHOR]

The investigation is dedicated to the detailed microstructure characterization of explosively welded clads, in which, exceptionally and for cognitive purposes, a very high detonation speed of about 2800 m/s was used to manufacture bimetallic aluminum-nickel plates. The study involves detailed microstructural characteristics of the bonded zone at micro and nano level, especially focused on the expanded melted regions consisted mostly of Al3Ni, Al3Ni2 and AlNi phases. In situ heating experiment in transmission electron microscope allowed observing microstructure transformation revealing that additionally present metastable Al9Ni2 phase was transformed to Al3Ni and Al3Ni2. Microhardness measurements across the welded zone showed the increase of the microhardness of nickel alloy plate from 153 up to 170 HV when approaching to the Ni201/A1050 interface, while the value for aluminum plate was of 45 HV. Within the melted zones the microhardness was found to be 135 HV and it enormously increased to 850 HV after annealing of the sample at 500 °C. This change was due to the transformation of the interface region from the waves with the melted zones into the continuous layers of two intermetallic phases: Al3Ni and Al3Ni2. The second phase grew at the expense of the Al3Ni. [ABSTRACT FROM AUTHOR]

β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis. Herein, we identify two asparagine-linked glycosylation sites in B4GalT4. We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion. Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans. We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version. [ABSTRACT FROM AUTHOR]

Our recent investigation uncovered that the acid ceramidase inhibitor LCL521 enhances the direct tumor cell killing effect of photodynamic therapy (PDT) treatment. The present study aimed at elucidating the mechanisms underlying this effect. Exposing mouse squamous cell carcinoma SCCVII cells treated with temoporfin-based PDT to LCL521 (rising ceramide concentration) produced a much greater decrease in cell survival than comparable exposure to the sphingosine kinase-1 inhibitor PF543 (that reduces sphingosine-1-phosphate concentration). This is consistent with recognizing the rising levels of pro-apoptotic sphingolipid ceramide as being more critical in promoting the death of PDT-treated cells than the reduction in the availability of pro-survival acting sphingosine-1 phosphate. This pro-apoptotic impact of LCL521, which was suppressed by the apoptosis inhibitor bongkrekic acid, involves the interaction with the cellular stress signaling network. Hence, inhibiting the key elements of these pathways markedly influenced the adjuvant effect of LCL521 on the PDT response. Particularly effective was the inositol-requiring element-1 (IRE1) kinase inhibitor STF-083010 that dramatically enhanced the killing of cells treated with PDT plus LCL521. An important role in the survival of these cells was exhibited by master transcription factors STAT3 and HIF-1α. The STAT3 inhibitor NSC 74859 was especially effective in further reducing the cell survival rates, suggesting its possible exploitation for therapeutic gain. An additional finding in this study is that LCL521-promoted PDT-mediated cell killing through ceramide-mediated lethal effects is extended to the interaction with other cancer treatment modalities with a rapid cellular stress impact such as photothermal therapy (PTT) and cryoablation therapy (CAT). [ABSTRACT FROM AUTHOR]

Explosive welding is a joining method suitable for materials difficult or impossible to connect using traditional welding techniques. In this work, the microstructure details occurring in the neighborhood of the aluminum (A1050) and nickel (Ni201) alloys' interfaces in explosive welds were described. It was shown that using appropriate welding conditions, although the mutual localization of the colliding plates was different, the microstructure of the bonded zone did not change. Moreover, further annealing of the samples at 500 °C revealed the microstructure transformation occurring as a result of the diffusion phenomena. This in turn provides the details essential in proper designing of the multilayers of metallic–intermetallic Al/Ni composites. [ABSTRACT FROM AUTHOR]

A careful substrate preparation and the physical properties of the coating particles are decisive for the quality and envisaged properties of the deposited layer. Temperature, size, rate and velocity represent the classical quantities, which can be measured in situ using various diagnostics. Nonetheless, another quality-determining parameter is the degree of oxidation which could not be measured in situ (up to now) by established diagnostics and must therefore be qualitatively derived from the above-mentioned quantities or subsequently be measured by means of destructive methods. Within this work, a diagnostic approach to determine in-flight particle oxidation has been outlined and tested. The presented measurement method detects the entire particle plume from different directions using a 2D two-color pyrometry and allows for the calculation of spatially resolved 3D temperature and intensity distributions based on a tomographic evaluation method. By additionally using measurements of the particle velocities and particle sizes, the surface emissivity of the particles along the spraying direction can be calculated, which in turn allows quantitative conclusions on the degree of particle oxidation. Investigations on the wire arc spraying process have shown that particle oxidation degrees could be determined and tend to correlate well with oxide contents in finished coatings. [ABSTRACT FROM AUTHOR]

Diagnostic methods using a tomographic reconstruction allow for three-dimensional characterization of spraying processes. Since in many spraying applications, non-rotationally symmetric phenomena occur, the application of emission tomography methods seems most reasonable. Yet, to be able to apply this method the observed object has to be luminous and optically thin. Hence, to investigate a particle stream, the optical thickness of such a stream has to be estimated beforehand. Within this paper, a method to determine this parameter, based on particle rate, size and velocity measurements is presented and applied to a wire arc spray process, proving that it is possible to perform a tomographic investigation of a particle beam. [ABSTRACT FROM AUTHOR]

Studies designed to examine effects of fat mass reduction (including lipodystrophy and lipectomy) on human serum total and LDL-cholesterol concentrations are inconsistent. The purpose of this study was to examine effect of partial lipectomy in rats (as an experimental model of fat mass reduction in humans) on (1) circulating total cholesterol, LDL-cholesterol + VLDL-cholesterol and HDL-cholesterol concentrations, and (2) factors which may affect serum cholesterol concentrations such as: (a) liver LDL-receptor level, (b) expression of liver PCSK9 and (c) circulating PCSK9 concentration. Reduction of rat adipose tissue mass resulted in an increase in circulating total and LDL + VLDL—cholesterol concentrations, which was associated with (a) decrease in liver LDL-R level, (b) increase in liver PCSK9 expression, and (c) increase in circulating PCSK9 concentration as compared with sham controls. These changes were accompanied by elevated liver HNF1α (and HNF4α) mRNA levels. Silencing HNF1α in HepG2 cells by siRNA led to decrease in PCSK9 mRNA levels. This suggests that overexpression of HNF1α gene in liver of lipectomized rats can lead to overproduction of PCSK9. In conclusion, up-regulation of PCSK9, due to overexpression of HNF1α gene in liver of lipectomized rats and subsequently increase in circulating PCSK9 concentration lead to decrease in liver LDL-R level. This may contribute, at least in part, to an increase in the concentration of circulating cholesterol in rats with reduced fat mass. These findings provide a possible explanation for the molecular mechanism of hypercholesterolemia observed sometimes after reduction of fat mass in human. [ABSTRACT FROM AUTHOR]

The procedure of numerical identification of thermophysical properties of concrete during its hardening is presented. Heat of cement hydration, thermal conductivity and specific heat are determined for purpose of modelling temperature evolution in massive concrete elements. The developed method is based on point temperature measurements in a cylindrical mould and the numerical solution of the inverse heat transfer problem by means of direct search optimization algorithm. The determined thermal characteristics of concrete are not constant and depend on the maturity of concrete. The procedure was verified on set of concrete mixes designed with Portland cement CEM I 42.5R and Portland-slag cement CEM II/B-S 32.5 N. Calcareous fly ash was also used for partial replacement of cement in the mixtures. The obtained results have been compared with experimentally measured temperature in concrete and a fair agreement has been found. [ABSTRACT FROM AUTHOR]

Ectromelia virus (ECTV) is an orthopoxvirus that productively replicates in dendritic cells (DCs), but its influence on the microtubule (MT) cytoskeleton in DCs is not known. Here, we show that ECTV infection of primary murine granulocyte-macrophage colony stimulating factor-derived bone marrow cells (GM-BM) downregulates numerous genes engaged in MT cytoskeleton organization and dynamics. In infected cells, the MT cytoskeleton undergoes dramatic rearrangement and relaxation, accompanied by disappearance of the microtubule organizing centre (MTOC) and increased acetylation and stabilization of MTs, which are exploited by progeny virions for intracellular transport. This indicates a strong ability of ECTV to subvert the MT cytoskeleton of highly specialized immune cells. [ABSTRACT FROM AUTHOR]

Ceramides are important participants of signal transduction, regulating fundamental cellular processes. Here we report the mechanism for activation of p53 tumor suppressor by C16-ceramide. C16-ceramide tightly binds within the p53 DNA-binding domain (Kd ~ 60 nM), in close vicinity to the Box V motif. This interaction is highly selective toward the ceramide acyl chain length with its C10 atom being proximal to Ser240 and Ser241. Ceramide binding stabilizes p53 and disrupts its complex with E3 ligase MDM2 leading to the p53 accumulation, nuclear translocation and activation of the downstream targets. This mechanism of p53 activation is fundamentally different from the canonical p53 regulation through protein–protein interactions or posttranslational modifications. The discovered mechanism is triggered by serum or folate deprivation implicating it in the cellular response to nutrient/metabolic stress. Our study establishes C16-ceramide as a natural small molecule activating p53 through the direct binding. [ABSTRACT FROM AUTHOR]