Amyloid management by chaperones: The mystery underlying protein oligomers' dual functions.

Protein oligomerization has two notable aspects: it is crucial for the performing cellular and molecular processes accurately, and it produces amyloid fibril precursors. Although a clear explanation for amyloidosis as a whole is lacking, most studies have emphasized the importance of protein misfolding followed by formation of cytotoxic oligomer structures, which are responsible for disorders as diverse as neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and metabolic disorders, such as type 2 diabetes. Constant surveillance by oligomeric protein structures known as molecular chaperones enables cells to overcome the challenge of misfolded proteins and their harmful assemblies. These molecular chaperones encounter proteins in cells, and benefit cell survival as long as they perform correctly. Thus, this review highlights the roles of structural aspects of chaperone protein oligomers in determining cell fate-either succumbing to amyloid oligomers or survival-as well as experimental approaches used to investigate these entities.

The Effect of Single-Anastomosis Sleeve Ileal (SASI) Bypass on Patients with Severe Obesity in Three Consecutive Years.

BACKGROUND: Sparse data are available regarding the efficacy and safety of single anastomosis sleeve ileal (SASI) bypass surgery, where most available studies utilized short-term follow-ups. Therefore, this study was conducted to evaluate the safety and outcomes of this procedure in three consecutive years after the surgery. MATERIALS AND METHODS: This retrospective study was carried out with 116 patients who underwent SASI from October 2016 to September 2021. Anthropometric, clinical, and biochemical data were recorded before, 1, 2, and 3 years after surgery. RESULTS: The 1, 2, and 3-year percentage of excess weight loss (%EWL) were 87.37%, 90.7%, and 80.6%, respectively. Remission or improvement was recorded for diabetes mellitus in 90.9%, hypertension in 80.0%, hyperlipidemia in 100%, sleep apnea in 100%, and irregular menstruation in 58.06 at 3 years after surgery. No mortality and 5.1% early major postoperative complications were recorded. Eight patients (6.8%) had reversal surgery due to EWL > 100%. CONCLUSIONS: The SASI bypass is an effective bariatric surgery that achieved sequential weight loss and improvement in medical comorbidities three years after the surgery; however, standardization of SASI procedure technique is needed to ameliorate nutritional deficiencies.

Lipid-driven condensation and interfacial ordering of FUS.

Protein condensation into liquid-like structures is critical for cellular compartmentalization, RNA processing, and stress response. Research on protein condensation has primarily focused on membraneless organelles in the absence of lipids. However, the cellular cytoplasm is full of lipid interfaces, yet comparatively little is known about how lipids affect protein condensation. Here, we show that nonspecific interactions between lipids and the disordered fused in sarcoma low-complexity (FUS LC) domain strongly affect protein condensation. In the presence of anionic lipids, FUS LC formed lipid-protein clusters at concentrations more than 30-fold lower than required for pure FUS LC. Lipid-triggered FUS LC clusters showed less dynamic protein organization than canonical, lipid-free FUS LC condensates. Lastly, we found that phosphatidylserine membranes promoted FUS LC condensates having ß sheet structures, while phosphatidylglycerol membranes initiated unstructured condensates. Our results show that lipids strongly influence FUS LC condensation, suggesting that protein-lipid interactions modulate condensate formation in cells.

Effect of type of fatty acid attached to chitosan on walnut oil-in-water Pickering emulsion properties.

The effect of fatty acid type bonded to chitosan on the emulsifying properties of chitosan-based particles was investigated. Capric acid, myristic acid, and stearic acid were attached to chitosan chains. Longer fatty acids in the structure of chitosan lead to the better and more uniform formation of chitosan nanogels. The contact angle of chitosan, chitosan-capric acid, chitosan-myristic acid and chitosan-stearic acid were found to be 52.5°, 60.0°, 65.1° and 72.5°, respectively. Different chitosan nanogels were used to stabilize walnut oil emulsions, and the emulsion stabilized with chitosan-stearic acid nanogels had the lowest creaming index (15.2%). Stabilized emulsions with chitosans attached to longer chain acids were more adapted to the mechanism of Pickering emulsions, in addition to having higher viscosity as well as more gel-like behavior. In general, this study showed that emulsifying properties of chitosan could be improved by increasing the number of fatty acid carbons bonded to chitosan.

The Trend of Interpersonal Violence Mortality at National and Provincial Levels in Iran From 1990 to 2015.

Interpersonal violence (IPV) is a major public health concern with a significant impact on physical and mental health. This study was designed to evaluate age-sex-specific IPV mortality trends and the assault mechanisms (firearm, sharp objects, and other means), at national and provincial levels, in Iran. We used the Iranian Death Registration System (DRS) and the population and housing censuses in this analysis. Spatio-temporal and Gaussian Process Regression methods were used to adjust for inconsistencies at the provincial level and to integrate data from various sources. After assessing their validity, all records were reclassified according to the International Classification of Diseases, 10th Revision (ICD-10). All ICD-10 codes were then mapped to Global Burden of Disease (GBD) 2013 coding. More than 700 individuals died due to IPV in 1990 and more than twice this number in 2015. The IPV mortality age-standardized rate, per 100,000, increased from 1.62 (95% Uncertainty Interval [UI] = [0.96, 2.75]) in 1990 to 1.81 [1.15, 2.89] in 2015. Among females, the age-standardized mortality rate at national level per 100,000 due to IPV was 1.27 [0.66, 2.43] in 1990 and decreased to 1.08 [0.60, 1.96] in 2015. Among males, the age-standardized mortality rate was 1.96 [1.25, 3.09] in 1990 rising to 2.54 [1.70, 3.82] in 2015. Data from provinces revealed that during the period of our study, Hormozgan province had the largest increase of IPV among females, and Fars province had the largest increase of IPV among males. Conversely, the largest decrease was detected in West Azarbaijan and Qom provinces in females and males, respectively. This study showed a wide variation in the incidence and trends of IPV in Iran by age, sex, and location. The study has provided valuable information to reduce the burden of IPV in Iran and a means to monitor future progress through repeated analyses of the trends.

Mining of camel rumen metagenome to identify novel alkali-thermostable xylanase capable of enhancing the recalcitrant lignocellulosic biomass conversion.

The aim of this study was to isolate and characterize novel alkali-thermostable xylanase genes from the mixed genome DNA of camel rumen metagenome. In this study, a five-stage computational screening procedure was utilized to find the primary candidate enzyme with superior properties from the camel rumen metagenome. This enzyme was subjected to cloning, purification, and structural and functional characterization. It showed high thermal stability, high activity in a broad range of pH (6-11) and temperature (30-90 °C) and effectivity in recalcitrant lignocellulosic biomass degradation. Our results demonstrated the power of in silico analysis to discover novel alkali-thermostable xylanases, effective for the bioconversion of lignocellulosic biomass.

Identification and characterization of a novel thermostable xylanase from camel rumen metagenome.

Metagenomics has emerged to isolate novel enzymes from the uncultured microbiota in the environment. In this study, the metagenomic data obtained from camel rumen was considered as the potential source of microbial xylanase enzymes with proper activity in extreme conditions. The metagenomic data were assembled and contigs were used for in-silico identification of candidate thermostable enzyme. A novel thermostable xylanase enzyme, named PersiXyn1, with 1146 bp full-length gene which encodes a 381 amino acid protein was identified. Using the DNA template extracted from camel rumen metagenomic samples, the candidate enzyme genes were cloned and expressed in proper E. coli strains. The phylogenetic analysis showed the evolutionary position of PersiXyn1 among the known thermostable xylanases. The results of the CD analysis and determining the secondary structure of the enzyme, confirmed the presence of a high percentage of ß-sheets as an important characteristic of thermophilic xylanases. The PersiXyn1 was active at a broad range of pH (6-11) and temperature (25-90 °C). The optimum pH and temperature were 8 and 40 °C respectively, and the enzyme maintained 80% of its maximum activity in the pH 8 and temperature 40 °C for 1 h. The Scanning electron microscope (SEM) micrograph of enzyme treated pulp clearly showed that the effective use of enzymes in fiber separation may reduce the cost of carton paper production. The novelty of this enzyme lies in the fact that it is highly active and stable in a broad range of pH and temperature. This study highlights the potential importance of camel microbiome for discovering novel thermostable enzymes with applications in agriculture and industries.

Comparative molecular dynamic simulation study on the use of chitosan for temperature stabilization of interferon αII.

Carbohydrate biopolymer of biocompatible biodegradable chitosan, currently become one of the most usable polymer in medical and pharmaceutical sciences. In this regard a large number of protein and peptide drugs are used as therapeutic agents which can be exposed to temperature stresses either in transporting or storage. These stresses can make the protein structure unstable, change the active structure and disrupt its therapeutic function that limits their using as successful drug. In order to overcome these disadvantages associated with protein drugs, different materials such as natural or synthetic polymers are used to make protein loaded biocompatible nano and microspheres. In this research, molecular dynamics simulations were used to study the effects of chitosan with different degree of deacetylation on the stability of Interferon αII structure at high temperature and compare its results with those of commonly used biocompatible synthetic polymers of Poly Ethylene Glycol and Poly Lactic-Co-Glycolic Acid. In these simulations, the conformational changes at high temperatures (343 K) and in the presence and absence of polymers were compared to data related to protein in normal temperature (300 K). In brief, and according to the results, it can be said that low deacetylated chitosan and poly lactic co-glycolic acid are more successful in terms of protein stability at high-temperature. It is also observed that Poly Ethylene Glycol has penetrated into the protein and shows some instability of protein conformation. Eventually, according to the findings of this study, low deacetylated chitosan and Poly Lactic-Co-Glycolic Acid are the preferable copolymers for using in protein delivery systems of this drug.