α-Crystallin B (CRYAB or HspB5) is a chaperone member of the small heat-shock protein family that prevents aggregation of many cytosolic client proteins by means of its ATP-independent holdase ...activity. Surprisingly, several reports show that CRYAB exerts a protective role also extracellularly, and it has been recently demonstrated that CRYAB is secreted from human retinal pigment epithelial cells by an unconventional secretion pathway that involves multi-vesicular bodies. Here we show that autophagy is crucial for this unconventional secretion pathway and that phosphorylation at serine 59 residue regulates CRYAB secretion by inhibiting its recruitment to the autophagosomes. In addition, we found that autophagosomes containing CRYAB are not able to fuse with lysosomes. Therefore, CRYAB is capable to highjack and divert autophagosomes toward the exocytic pathway, inhibiting their canonical route leading to the lysosomal compartment. Potential implications of these findings in the context of disease-associated mutant proteins turn-over are discussed.
Powder metallurgy stands out as a preferred manufacturing method across various industries due to its advantages in design flexibility, material efficiency, and cost-effective production. In this ...work, we study the influence of different compaction directions on the strength characteristics of parts produced using powder metallurgy. Al–4 wt.%Cu alloys are used due to their recyclability. We use three distinctive compaction pressures. After sintering, samples are either air-cooled or water-quenched and naturally aged (T4 temper). Both the compressive and tensile strengths are characterized and thoroughly analyzed. This research highlights the significant impact of both heat treatments and compaction directions on anisotropic strengths. The novelty of this research lies in the use of powders that can be reclaimed from machining, turning, or foundry rejections. By eliminating or minimizing the melting stage and employing powder metallurgy, we achieve cost-effective and environmentally friendly processes. Furthermore, we underscore the critical role played by careful planning of compaction loads, compaction directions, and heat treatments in determining the final mechanical performance. This approach is not only economically viable but also aligns with the growing adoption of environmental, social, and governance (ESG) practices in industry.
This investigation focuses on the effects of the compaction directions (i.e., transversal and longitudinal) and microstructural arrays (inside the powder utilized to constitute the specimens) on the ...anisotropic strengths. The initial powders are obtained from the as-cast Al-4 wt.% Cu alloys solidified in two distinct cooling rates, i.e., ~0.5 and 2.5 °C/s. The powder particles are compacted by using 300, 400 and 600 MPa and sintered at 540 °C for 1 h. The compressive and tensile strengths are carried out and the anisotropic strengths are determined. It is found that transverse samples exhibit higher UCS (ultimate compressive strength) and UTS (ultimate tensile strength) than the longitudinal samples. It is also found that the powder compacted in the transversal direction and utilizing powder with finer dendritic arm spacing provides better UCS and UTS results. The novelty in the study concerns the fact that is evidenced in the role of the dendrite spacings concatenated with the compaction pressure and direction upon the mechanical behavior. It is concluded that depending on the compaction level intended or demanded mechanical behavior, the planning in the compaction direction is preprogrammed. Since recycled powder particles from conventional machining, drilling and turning can potentially be utilized to constitute parts and components, the environmentally friendly aspects are associated, and hazardous stages in a manufacturing process are substantially reduced or eliminated.
The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration ...(APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 ± 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 ± 0.5 μmol/L vs 0.53 ± 0.14 μmol/L; p < 0.01), HCys (15 ± 7.6 μmol/L vs 6.8 ± 3 μmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson‘s R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This experimental investigation is focused on the evaluation of the compressive strength and corrosion behavior of Al-5Cu/xCu composites with Cu content, varying of 0, 1, 3, and 5 wt.% Cu. Powder of ...an as-cast Al-5Cu alloy is used to constitute Al-5Cu/xCu composites. EIS parameters and potentiodynamic polarization curves in a stagnant 0.5 M NaCl solution at 25 °C are discussed. It is found that Cu content significantly affects the resulting mechanical and corrosion properties. The increase of Cu content decreases the compressive strength. The highest corrosion resistance and mechanical-to-corrosion ratio are that of the Al-5Cu/3Cu composite.
This paper is focused on the effect of distinctive compaction pressures and Si content on the resulting morphologies and compressive strengths (CS) of the sintered and quenched composites. The powder ...particles from the as-cast Al-9wt.%Si and Al-5wt.%Cu alloys constituting recycled powders are used. A mixture 1:1 wt ratio between aforementioned casting alloys is also examined. With the applied compaction pressure, the resulting microstructural array has no modified. After heat-treating, the chemical content has important role on the mechanical behavior. It is found that the CS increases with the increase of the compaction pressure. Also, when the Al–5Cu alloy powder is used, the highest CS is attained. The intermediate CS is that of the mixture composite (1:1) and the lowest is obtained when the Al–9Si sample powder is used. The specific strengths are also determined, which favor the composite constituted by the Al–5Cu alloy powder. This induces both the economical and environmental-friendly aspects intending to produce engineering components using as-recycled powders.
KCNQ2 and KCNQ3 K+ channel subunits underlie the muscarinic-regulated K+ current (IKM), a widespread regulator of neuronal excitability. Mutations in KCNQ2- or KCNQ3-encoding genes cause benign ...familiar neonatal convulsions (BFNCs), a rare autosomal-dominant idiopathic epilepsy of the newborn. In the present study, we have investigated, by means of electrophysiological, biochemical, and immunocytochemical techniques in transiently transfected cells, the consequences prompted by a BFNC-causing 1-bp deletion (2043ΔT) in the KCNQ2 gene; this frameshift mutation caused the substitution of the last 163 amino acids of the KCNQ2 C terminus and the extension of the subunit by additional 56 residues. The 2043ΔT mutation abolished voltage-gated K+ currents produced upon homomeric expression of KCNQ2 subunits, dramatically reduced the steady-state cellular levels of KCNQ2 subunits, and prevented their delivery to the plasma membrane. Metabolic labeling experiments revealed that mutant KCNQ2 subunits underwent faster degradation; 10-h treatment with the proteasomal inhibitor MG132 (20 μm) at least partially reversed such enhanced degradation. Co-expression with KCNQ3 subunits reduced the degradation rate of mutant KCNQ2 subunits and led to their expression on the plasma membrane. Finally, co-expression of KCNQ2 2043ΔT together with KCNQ3 subunits generated functional voltage-gated K+ currents having pharmacological and biophysical properties of heteromeric channels. Collectively, the present results suggest that mutation-induced reduced stability of KCNQ2 subunits may cause epilepsy in neonates.
The aim of this investigation is focused on the evaluation of the effect of two distinctive sizes and morphologies of powder particles from the recycled as-cast Al-Si and Al-Cu alloys. Elemental ...powders from Al-9Si, Al-5Cu alloys and a mixture 1:1 weight ratio between aforementioned casting alloys to constitute alloy powder composites are used. It is found that the sintered densification of coarser powders provides slight higher densification than finer particles. It is also confirmed a strength anisotropic effect when the tensile and compressive are evaluated. Tensile strength reveals that finer particles provide better mechanical behavior. It is clearly evidenced that the solute content affects the compressive strengths, which favors the Al-5Cu alloy powder composite (∼140 MPa). The lowest compressive behavior is that of the Al-9Si sample (∼105 MPa), and the intermediate is that of the Al-4.5Si-2.5Cu composite (∼120 MPa). These results are intimately associated with the formed clusters of brittle Si particles inducing to microcracks at the Al-9Si alloy composite. Additionally, the specific strengths of the examined composites are determined, and the Al-5Cu composite demonstrates interesting economical and environmental-friendly characteristics.
•Composites from elemental powder particles from as-cast Al-Si and Al-Cu alloys are produced.•Green and sintered densifications of Al-Si, Al-Cu and a mixture 1:1 alloys composites are evaluated.•Distinctive powder sizes and morphologies are evaluated.•Recycled Al-based alloys can be reused to constitute automobile and aerospace components.
This investigation is focused on the characterization of distinct environmental-friendly Alp/Sip composites. Differently from the traditional Al/Si composites, which are produced with Al-based alloy ...castings, the investigated composites are elaborated using Al and Si powder particles, sequentially compacted and sintered. The green and sintered densifications are determined, which are affected by both Si content and the applied compaction load. The preprogramming of the compaction pressure and sintering time induce to similar ultimate tensile strength (UTS) of an Al-Si casting alloy. The specific strength per relative manufacturing cost comparing with Al/SiC composites is also shown. Since the restriction legislations have banned hazardous materials, the proposed Al composites have an environmental-friendly aspect associated with a low manufacturing cost and recycling aspect.
Display omitted
•Green and sintered densifications for three distinctive Al/Sip composites are evaluated.•Si content and sintered density have important role on the mechanical behavior.•Mechanical behavior similar to Al-Si casting alloy can be planned and attained.•Environmentally-friendly Al/Sip composites are produced by powder metallurgy route.
The present study was designed to establish the relationship between personality factors, socio-economic factors and acute life stress with development, spontaneous cardioversion and recurrences of ...acute lone atrial fibrillation.
The study group consisted of 116 patients with lone atrial fibrillation cardioverted within 48h of the onset of arrhythmia; they underwent a series of cognitive tests to evaluate acute psychological stress and personality type. The socio-economic status and other covariates (alcohol consumption, smoking, and body mass index) were investigated. A control group, age- and sex-matched, was selected and compared. In the logistic regression analysis, the presence of spontaneous conversion to sinus rhythm was used as the dependent variable. Independent variables were indicator variables representing categories of stress, Type A behaviour pattern, coffee consumption and body mass index. Variables considered for logistic analysis were only those with independent prognostic value.
Type A behaviour pattern was found in 23 (20%) patients with atrial fibrillation and in 11 (9%) controls (P<0.001). The mean score among patients with atrial fibrillation was 8+/-2.7, while in control subjects it was 5.5+/-2. The mean acute life stress score among patients with atrial fibrillation was 56+/-33, while in controls it was 34+/-27 (P<0.01). Spontaneous conversion of atrial fibrillation to sinus rhythm was observed in 72 patients (63%). In univariate analysis alcohol consumption, income, education and smoking habits did not affect spontaneous conversion. High coffee consumption (OR 0.3 95% CI 0.11-0.49; P<0.008) and high body mass index were associated with a significantly greater risk of atrial fibrillation (OR 1.5 95% CI 1.2-1.7).
Type A behaviour pattern and acute life stress affect the development and spontaneous conversion of atrial fibrillation. Patients with acute stress showed the highest probability of spontaneous conversion followed by patients with Type A behaviour. Other socio-economic factors affect spontaneous conversion and recurrences of lone atrial fibrillation to a lesser extent.
PDF
