scholarly journals Association of partially folded lens βB2-crystallins with the α-crystallin molecular chaperone

2008 ◽  
Vol 409 (3) ◽  
pp. 691-699 ◽  
Author(s):  
Paul Evans ◽  
Christine Slingsby ◽  
B. A. Wallace
Keyword(s):  
Light Scattering ◽  
Molecular Chaperone ◽  
Structural Model ◽  
High Efficiency ◽  
Elevated Temperatures ◽  
Quaternary Structure ◽  
Low Protein ◽  
Age Related ◽  
Partially Folded Intermediate

Age-related cataract is a result of crystallins, the predominant lens proteins, forming light-scattering aggregates. In the low protein turnover environment of the eye lens, the crystallins are susceptible to modifications that can reduce stability, increasing the probability of unfolding and aggregation events occurring. It is hypothesized that the α-crystallin molecular chaperone system recognizes and binds these proteins before they can form the light-scattering centres that result in cataract, thus maintaining the long-term transparency of the lens. In the present study, we investigated the unfolding and aggregation of (wild-type) human and calf βB2-crystallins and the formation of a complex between α-crystallin and βB2-crystallins under destabilizing conditions. Human and calf βB2-crystallin unfold through a structurally similar pathway, but the increased stability of the C-terminal domain of human βB2-crystallin relative to calf βB2-crystallin results in the increased population of a partially folded intermediate during unfolding. This intermediate is aggregation-prone and prevents constructive refolding of human βB2-crystallin, while calf βB2-crystallin can refold with high efficiency. α-Crystallin can effectively chaperone both human and calf βB2-crystallins from thermal aggregation, although chaperone-bound βB2-crystallins are unable to refold once returned to native conditions. Ordered secondary structure is seen to increase in α-crystallin with elevated temperatures up to 60 °C; structure is rapidly lost at temperatures of 70 °C and above. Our experimental results combined with previously reported observations of α-crystallin quaternary structure have led us to propose a structural model of how activated α-crystallin chaperones unfolded βB2-crystallin.

Stacking of Bi2Te3 and FeSi2 for Thermoelectric Applications

2005 ◽  
Vol 492-493 ◽  
pp. 273-280 ◽  
Author(s):  
Cestmir Drasar ◽  
Eckhard Müller
Keyword(s):  
High Efficiency ◽  
Elevated Temperatures ◽  
Mechanical Stability ◽  
Negative Impact ◽  
Coefficient Of Thermal Expansion ◽  
Thermal Contact ◽  
Dissimilar Materials ◽  
Thermoelectric Device ◽  
High Electrical Resistivity

Recently, there is a strong interest in developing superior thermoelectric materials with the aim to improve the performance of a thermoelectric device. However, the performance of a thermoelectric generator (TEG) can be considerably improved also by applying a graded composition along the temperature gradient inside the thermoelectric device so that at each position the respective material achieves its maximum thermoelectric performance (TE FGM principle). Combining the high efficiency of Bi2Te3 (used at low temperatures) and general durability of FeSi2 (applied up to high temperatures) will result in a thermoelectric device with enhanced efficiency operating in air at a wide temperature range. The challenge is to contact these dissimilar materials without any negative impact on the performance of TEG. Besides providing a good electrical and thermal contact between Bi2Te3 and FeSi2 the junctions have to remain mechanically and chemically stable over long term. A Bi2Te3-SiO2 composite interlayer was used to adjust the different coefficient of thermal expansion (CTE) of FeSi2 (≈ 7·10-6 K-1) and Bi2Te3 (≈ 19·10-6 K-1). Due to low chemical stability of the Bi2Te3/FeSi2 contact at elevated temperatures (1000 h @ 300°C) a contacting material (diffusion barrier) based on Ni, Zn, Ti, and ZnTe was tested. Some contacts show excellent chemical and mechanical stability, though the electrical properties of the contacts do not meet the requirements (e.g. ZnTe is a wide gap semiconductor with high electrical resistivity). According to very recent studies at the Zn-based diffusion barriers a very thin layer of undoped ZnTe growing at the Bi2Te3/Zn interface causes the deterioration of the contact resistance. Ideas solving this problem are outlined and discussed.

scholarly journals Augmentation of Bri2 molecular chaperone activity against amyloid-β reduces neurotoxicity in mouse hippocampus in vitro

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Gefei Chen ◽  
Yuniesky Andrade-Talavera ◽  
Simone Tambaro ◽  
Axel Leppert ◽  
Harriet E. Nilsson ◽  
...  
Keyword(s):  
Molecular Chaperone ◽  
Molecular Chaperones ◽  
Quaternary Structure ◽  
Therapeutic Potential ◽  
Amyloid Β ◽  
Network Activity ◽  
Amyloid Β Peptide ◽  
Neuronal Network Activity ◽  
Age Related

AbstractMolecular chaperones play important roles in preventing protein misfolding and its potentially harmful consequences. Deterioration of molecular chaperone systems upon ageing are thought to underlie age-related neurodegenerative diseases, and augmenting their activities could have therapeutic potential. The dementia relevant domain BRICHOS from the Bri2 protein shows qualitatively different chaperone activities depending on quaternary structure, and assembly of monomers into high-molecular weight oligomers reduces the ability to prevent neurotoxicity induced by the Alzheimer-associated amyloid-β peptide 1-42 (Aβ42). Here we design a Bri2 BRICHOS mutant (R221E) that forms stable monomers and selectively blocks a main source of toxic species during Aβ42 aggregation. Wild type Bri2 BRICHOS oligomers are partly disassembled into monomers in the presence of the R221E mutant, which leads to potentiated ability to prevent Aβ42 toxicity to neuronal network activity. These results suggest that the activity of endogenous molecular chaperones may be modulated to enhance anti-Aβ42 neurotoxic effects.

To the 70th anniversary of World Meteorological Organization. Scientific and technical cooperation of Hydrometeorological Center of the USSR/Russia in the Programs of World Meteorological Organization

2020 ◽  
pp. 117-138
Author(s):  
S.V. Borshch ◽  
◽  
R.M. Vil’fand ◽  
D.B. Kiktev ◽  
V.M. Khan ◽  
...  
Keyword(s):  
Environmental Monitoring ◽  
High Efficiency ◽  
World Meteorological Organization ◽  
70Th Anniversary ◽  
Technical Level ◽  
Technical Cooperation ◽  
Wide Range

The paper presents the summary and results of long-term and multi-faceted experience of international scientific and technical cooperation of Hydrometeorological Center of Russia in the field of hydrometeorology and environmental monitoring within the framework of WMO programs, which indicates its high efficiency in performing a wide range of works at a high scientific and technical level. Keywords: World Meteorological Organization, major WMO programs, representatives of Hydrometeorological Center of Russia in WMO

Recent advances in the analysis full/empty capsid ratio and genome integrity of adeno-associated virus (AAV) gene delivery vectors

2020 ◽  
Vol 20 ◽  
Author(s):  
L. Hajba ◽  
A. Guttman
Keyword(s):  
Gene Delivery ◽  
High Efficiency ◽  
Analytical Techniques ◽  
Viral Gene ◽  
Adeno Associated Virus ◽  
Gene Delivery Vectors ◽  
Empty Capsid ◽  
Purification Methods ◽  
Viral Gene Delivery

: Adeno-associated virus (AAV) is one of the most promising viral gene delivery vectors with long-term gene expression and disease correction featuring high efficiency and excellent safety in human clinical trials. During the production of AAV vectors,there are several quality control (QC)parameters that should be rigorously monitored to comply with clini-cal safety and efficacy. This review gives a short summary of the most frequently used AVV production and purification methods,focusing on the analytical techniques applied to determine the full/empty capsid ratio and the integrity of the encapsidated therapeutic DNA of the products.

scholarly journals High-efficiency CO2 separation using hybrid LDH-polymer membranes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaozhi Xu ◽  
Jiajie Wang ◽  
Awu Zhou ◽  
Siyuan Dong ◽  
Kaiqiang Shi ◽  
...  
Keyword(s):  
Self Assembly ◽  
High Efficiency ◽  
Transmission Rate ◽  
Spray Coating ◽  
Separation Performance ◽  
Pdms Layer ◽  
Operational Testing ◽  
Enhanced Solubility ◽  
Double Hydroxide

AbstractMembrane-based gas separation exhibits many advantages over other conventional techniques; however, the construction of membranes with simultaneous high selectivity and permeability remains a major challenge. Herein, (LDH/FAS)n-PDMS hybrid membranes, containing two-dimensional sub-nanometre channels were fabricated via self-assembly of unilamellar layered double hydroxide (LDH) nanosheets and formamidine sulfinic acid (FAS), followed by spray-coating with a poly(dimethylsiloxane) (PDMS) layer. A CO2 transmission rate for (LDH/FAS)25-PDMS of 7748 GPU together with CO2 selectivity factors (SF) for SF(CO2/H2), SF(CO2/N2) and SF(CO2/CH4) mixtures as high as 43, 86 and 62 respectively are observed. The CO2 permselectivity outperforms most reported systems and is higher than the Robeson or Freeman upper bound limits. These (LDH/FAS)n-PDMS membranes are both thermally and mechanically robust maintaining their highly selective CO2 separation performance during long-term operational testing. We believe this highly-efficient CO2 separation performance is based on the synergy of enhanced solubility, diffusivity and chemical affinity for CO2 in the sub-nanometre channels.

scholarly journals Automatic detection of 39 fundus diseases and conditions in retinal photographs using deep neural networks

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ling-Ping Cen ◽  
Jie Ji ◽  
Jian-Wei Lin ◽  
Si-Tong Ju ◽  
Hong-Jie Lin ◽  
...  
Keyword(s):  
Deep Learning ◽  
High Efficiency ◽  
Characteristic Curve ◽  
Weighted Average ◽  
Age Related Macular Degeneration ◽  
Learning Platform ◽  
Age Related ◽  
Public Data ◽  
Primary Test ◽  
Retinal Fundus

AbstractRetinal fundus diseases can lead to irreversible visual impairment without timely diagnoses and appropriate treatments. Single disease-based deep learning algorithms had been developed for the detection of diabetic retinopathy, age-related macular degeneration, and glaucoma. Here, we developed a deep learning platform (DLP) capable of detecting multiple common referable fundus diseases and conditions (39 classes) by using 249,620 fundus images marked with 275,543 labels from heterogenous sources. Our DLP achieved a frequency-weighted average F1 score of 0.923, sensitivity of 0.978, specificity of 0.996 and area under the receiver operating characteristic curve (AUC) of 0.9984 for multi-label classification in the primary test dataset and reached the average level of retina specialists. External multihospital test, public data test and tele-reading application also showed high efficiency for multiple retinal diseases and conditions detection. These results indicate that our DLP can be applied for retinal fundus disease triage, especially in remote areas around the world.

scholarly journals The Hsp60 Protein of Helicobacter Pylori Exhibits Chaperone and ATPase Activities at Elevated Temperatures

BioChem ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 19-25
Author(s):  
Jose A. Mendoza ◽  
Julian L. Ignacio ◽  
Christopher M. Buckley
Keyword(s):  
Helicobacter Pylori ◽  
Heat Stress ◽  
Molecular Chaperone ◽  
Elevated Temperatures ◽  
Citrate Synthase ◽  
Gastric Epithelium ◽  
Acidic Conditions ◽  
H Pylori ◽  
Induced Aggregation ◽  
Hydrolysis Of

The heat-shock protein, Hsp60, is one of the most abundant proteins in Helicobacter pylori. Given its sequence homology to the Escherichia coli Hsp60 or GroEL, Hsp60 from H. pylori would be expected to function as a molecular chaperone in this organism. H. pylori is a type of bacteria that grows on the gastric epithelium, where the pH can fluctuate between neutral and 4.5, and the intracellular pH can be as low as 5.0. We previously showed that Hsp60 functions as a chaperone under acidic conditions. However, no reports have been made on the ability of Hsp60 to function as a molecular chaperone under other stressful conditions, such as heat stress or elevated temperatures. We report here that Hsp60 could suppress the heat-induced aggregation of the enzymes rhodanese, malate dehydrogenase, citrate synthase, and lactate dehydrogenase. Moreover, Hsp60 was found to have a potassium and magnesium-dependent ATPase activity that was stimulated at elevated temperatures. Although, Hsp60 was found to bind GTP, the hydrolysis of this nucleotide could not be observed. Our results show that Hsp60 from H. pylori can function as a molecular chaperone under conditions of heat stress.

scholarly journals CO Detection Investigation at High Temperature by SiC MISFET Metal/Oxide Gas Sensors

Proceedings ◽  
2021 ◽  
Vol 56 (1) ◽  
pp. 41
Author(s):  
Lida Khajavizadeh ◽  
Anita Lloyd Spetz ◽  
Mike Andersson
Keyword(s):  
High Temperature ◽  
Gas Sensors ◽  
Elevated Temperatures ◽  
Long Term Stability ◽  
Stability Performance ◽  
Catalytic Metal ◽  
Co Detection ◽  
Effect Transistor ◽  
Metal Oxide Gas Sensors

In order to investigate the necessary device improvements for high-temperature CO sensing with SiC metal insulator semiconductor field effect transistor (MISFET)-based chemical gas sensors, devices employing, as the gas-sensitive gate contact, a film of co-deposited Pt/Al2O3 instead of the commonly used catalytic metal-based contacts were fabricated and characterized for CO detection at elevated temperatures and different CO and O2 levels. It can be concluded that the sensing mechanism at elevated temperatures correlates with oxygen removal from the sensor surface rather than the surface CO coverage as observed at lower temperatures. The long-term stability performance was also shown to be improved compared to that of previously studied devices.

scholarly journals Crosstalk between Long-Term Sublethal Oxidative Stress and Detrimental Inflammation as Potential Drivers for Age-Related Retinal Degeneration

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Lara Macchioni ◽  
Davide Chiasserini ◽  
Letizia Mezzasoma ◽  
Magdalena Davidescu ◽  
Pier Luigi Orvietani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Rpe Cells ◽  
Age Related ◽  
Oxidative Insult

Age-related retinal degenerations, including age-related macular degeneration (AMD), are caused by the loss of retinal pigmented epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD, deeply linked to the aging process, also involves oxidative stress and inflammatory responses. However, the molecular mechanisms contributing to the shift from healthy aging to AMD are still poorly understood. Since RPE cells in the retina are chronically exposed to a pro-oxidant microenvironment throughout life, we simulated in vivo conditions by growing ARPE-19 cells in the presence of 10 μM H2O2 for several passages. This long-term oxidative insult induced senescence in ARPE-19 cells without affecting cell proliferation. Global proteomic analysis revealed a dysregulated expression in proteins involved in antioxidant response, mitochondrial homeostasis, and extracellular matrix organization. The analyses of mitochondrial functionality showed increased mitochondrial biogenesis and ATP generation and improved response to oxidative stress. The latter, however, was linked to nuclear factor-κB (NF-κB) rather than nuclear factor erythroid 2–related factor 2 (Nrf2) activation. NF-κB hyperactivation also resulted in increased pro-inflammatory cytokines expression and inflammasome activation. Moreover, in response to additional pro-inflammatory insults, senescent ARPE-19 cells underwent an exaggerated inflammatory reaction. Our results indicate senescence as an important link between chronic oxidative insult and detrimental chronic inflammation, with possible future repercussions for therapeutic interventions.

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