Activity Of Complexes Research Articles

Mechanisms Mediating the Combined Toxicity of Paraquat and Maneb in SH-SY5Y Neuroblastoma Cells.

Epidemiological and experimental studies have demonstrated that combined exposure to the pesticides paraquat (PQ) and maneb (MB) increases the risk of developing Parkinson's disease. However, the mechanisms mediating the toxicity induced by combined exposure to these pesticides are not well understood. The aim of this study was to investigate the mechanism(s) of neurotoxicity induced by exposure to the pesticides PQ and MB isolated or in association (PQ + MB) in SH-SY5Y neuroblastoma cells. PQ + MB exposure for 24 and 48 h decreased cell viability and disrupted cell membrane integrity. In addition, PQ + MB exposure for 12 h decreased the mitochondrial membrane potential. PQ alone increased reactive oxygen species (ROS) and superoxide anion generation and decreased the activity of mitochondrial complexes I and II at 12 h of exposure. MB alone increased ROS generation and depleted intracellular glutathione (GSH) within 6 h of exposure. In contrast, MB exposure for 12 h increased the GSH levels, the glutamate cysteine ligase (GCL, the rate-limiting enzyme in the GSH synthesis pathway) activity, and increased nuclear Nrf2 staining. Pretreatment with buthionine sulfoximine (BSO, a GCL inhibitor) abolished the MB-mediated GSH increase, indicating that MB increases GSH synthesis by upregulating GCL, probably by the activation of the Nrf2/ARE pathway. BSO pretreatment, which did not modify cell viability per se, rendered cells more sensitive to MB-induced toxicity. In contrast, treatment with the antioxidant N-acetylcysteine protected cells from MB-induced toxicity. These findings show that the combined exposure of SH-SY5Y cells to PQ and MB induced a cytotoxic effect higher than that observed when cells were subjected to individual exposures. Such a higher effect seems to be related to additive toxic events resulting from PQ and MB exposures. Thus, our study contributes to a better understanding of the toxicity of PQ and MB in combined exposures.

CKIP-1 mediates CK2 translocation to regulate Nav1.5 and Kir2.1 channel complexes in cardiomyocytes.

Sodium and potassium channels, especially Nav1.5 and Kir2.1, play key roles in the formation of action potentials in cardiomyocytes. These channels interact with, and are regulated by, synapse-associated protein 97 (SAP97). However, the regulatory role of SAP97 in myocyte remains incompletely understood. Here, we investigate the function of SAP97 phosphorylation in the regulation of Nav1.5 and Kir2.1 channel complexes and the upstream regulation of SAP97. We found that SAP97 is phosphorylated by casein kinase II (CK2) in vitro. In addition, transfection of casein kinase 2 interacting protein-1 (CKIP-1) into cardiomyocytes to drive CK2 from the nucleus to the cytoplasm, increased SAP97 phosphorylation and Nav1.5 and Kir2.1 current activity. These findings demonstrated that CKIP-1 modulates the subcellular translocation of CK2, which regulates Nav1.5 and Kir2.1 channel complex formation and activity in cardiomyocytes.

DNA cleaver with improved phosphatase and cytotoxic activity of a series of N2O‐based zinc(II) complexes

Three new Zn(II) Schiff base complexes, [ZnLCl2] (1), [ZnLBr2] (2) and [ZnL(SCN)2] (3), have been synthesized by adding Zn(II) salts of chloride and bromide to a compartmental ligand with NNO donor prepared through the simple condensation of pyridine‐2‐carboxaldehyde and a substituted aniline. The complexes have been identified using standard physicochemical methods, and their solid‐state structures have been determined through single‐crystal X‐ray analysis. The phosphatase‐like activity of all three complexes has been investigated using 4‐NPP as the model substrate in a DMSO/water medium. Complex 1 exhibits the highest level of phosphatase activity. The reactivity trend shows that complex 1 > complex 2 > complex 3. A plausible mechanism and the causes underlying the activity trend have been explored through DFT study, ESI‐mass spectra and 31P experiments. Complex 1 shows promising potential for use in gene‐targeted therapeutics due to its remarkable performance in DNA digestion. The excellent DNA cleavage result of complex 1 has led to the investigation of its molecular docking interaction with the liver cancer 2 receptor to study its anti‐liver cancer activity. Furthermore, in vitro anticancer activity of complex 1 also shows excellent antiproliferative activity against hepatocellular carcinoma.

Insights into Co (II)-based hybrid materials for photocatalytic and antioxidant applications

Metal-organic materials are widely used as scaffolds to create porous materials for various applications. However, research on solid compositions from hybrid materials (HB) is limited. This study examines two hybrid components using spectroscopic techniques and single crystal X-ray diffraction. The crystal structure analysis reveals a monoclinic system for compounds Co(HCO2)2·2H2O (I) and (C6H10N2)2[CoCl4]Cl2 (II) in the P21/c space group. Compound I features cobalt octahedra with coordinated formate ions and water molecules, while compound II contains organic cations, anions, and free chlorides with interconnected structural motifs. UV light at 400 nm induces high photocatalytic activity in both complexes, leading to significant degradation rates within 80 minutes. Trapping experiments identify activated species as h+ and •O2−. Antioxidant activity assessments highlight their antioxidative potentials.

АНАЛИЗ КЛЮЧЕВЫХ ОСОБЕННОСТЕЙ ЗЕМЛЕУСТРОИТЕЛЬНОГО ПРОЦЕССА В АГРОПРОМЫШЛЕННОМ КОМПЛЕКСЕ РОССИИ

The article discusses the key features of the land management process in the agro-industrial complex of the Russian Federation. The most important sources of features are identified, the structure of land relations, the specifics of the activities of economic entities in the field of agriculture, as well as the legal regulation of land relations, the role of technological innovation, geological and geographical features of the territory, and economic aspects are analyzed. The basic directions of the strategic initiative for the digitalization of agriculture are highlighted. The role of agrotechnoparks in the conditions of digital transformation of the land management process is determined. The priorities for resource support for land management activities in the agro-industrial complex are determined, taking into account modern technological conditions and the innovative activity of the scientific environment.

Neuroprotective effect of Orostachys spinose dry extract in cholinergic insufficiency

Background. Orostachys spinosa (L.) Sweet. – a perennial plant of a wide habitat and contains various metabolites (amino acids, flavonoids, polysaccharides, etc.). Extracts from the aerial part of the plant are used in traditional medicine as an anticonvulsant and sedative.The aim of the work. To study the neuroprotective effect of O. spinosa in cholinergic deficiency.Materials and methods. The studies were carried out on 52 Wistar rats. The animals were administered scopolamine (1 mg/kg) daily for 21 days, followed by O. spinosa dry extract per os at a dose of 100 mg/kg for 14 days. On the day 32, the animals developed a conditioned passive avoidance reflex (CPAR), the integrity of which was checked after 1, 24 and 72 hours; on the day 35 they were tested in an “open field”. On the day 36, biochemical and histological studies of the brain were carried out.Results. It has been established that O. spinosa, against the background of scopolamine intoxication, reduces the anxiety of animals, stimulates exploratory activity in the open field test, improves the production and preservation of the CPAR, and also reduces the number of functionally inactive neurons (pyknotic and shadow cells) in the cerebral cortex. The extract reduces the lactate/pyruvate ratio by 47 %, intensifies the activity of mitochondrial complexes I and II by 54–64 %, and increases the concentration of adenosine triphosphate by 1.6 times compared to the control. O. spinosa exhibits antioxidant properties by reducing malondialdehyde and increasing the activity of catalase, glutathione peroxidase and glutathione reductase in the brain.Conclusion. O. spinosa dry extract has a neuroprotective effect in cholinergic deficiency. The studied extract exhibits antioxidant properties and stimulates energy processes in the brain

Interference with PLA2G16 promotes cell cycle arrest and apoptosis and inhibits the reprogramming of glucose metabolism in multiple myeloma cells by modulating the Hippo/YAP signaling pathway.

Multiple myeloma, which is a clonal plasma cell tumor, derives from a postmitotic lymphoid B-cell lineage and remains untreatable. Group XVI phospholipase A2 (PLA2G16) can either be a tumor suppressor or an oncogene in different types of cancer. This study was intended to explore the role of PLA2G16 in multiple myeloma and to reveal the reaction mechanism. The mRNA and protein expressions of PLA2G16 in human bone marrow stromal cell line HS-5 and multiple myeloma cells were assessed using reverse transcription-quantitative PCR and western blot. The transfection efficacy of sh-PLA2G16 and oe-YAP was examined using reverse transcription-quantitative PCR and western blot. Through cell counting kit-8 assay and 5-ethynyl-2'- deoxyuridine staining, multiple myeloma cell viability and proliferation were detected. Flow cytometry was used to measure cell apoptosis and cell cycle distribution. Oxygen consumption rate, the activities of mitochondrial respiratory chain complexes I-V, and the activity of caspase-3 were estimated with Seahorse XF24 analyzer, oxidative phosphorylation activity assay kit, and caspase-3 assay kit, respectively. Lactate production and glucose consumption were evaluated usingcorresponding assay kits. Western blot was employed to meaure proteins associated with cell cycle, glycolysis, pentose phosphate pathway as well as Hippo/YAP signaling pathway. In this study, PLA2G16 expression was greatly increased in multiple myeloma cells and PLA2G16 silence inhibited cell proliferation, promoted cell apoptosis, facilitated cell cycle arrest, and suppressed the reprogramming of glucose metabolism in multiple myeloma. It was also identified that PLA2G16 depletion inhibited the Hippo/YAP signaling pathway. Further experiments revealed that the overexpression of YAP partially reversed the inhibitory effects of PLA2G16 silence on multiple myeloma cell malignant development and the reprogramming of glucose metabolism. Collectively, PLA2G16 silence impeded multiple myeloma progression and inhibited glucose metabolism reprogramming by blocking the Hippo/YAP signaling pathway.

Preparation and Performance Evaluation of Polysaccharide-Iron Complex of Eucommia ulmoides.

An innovative iron supplement crucial for treating iron-deficiency anemia was developed in this study. Polysaccharide was extracted from Eucommia ulmoides leaves using a microwave-assisted hot water method, and subsequently, the polysaccharide-iron complex was synthesized through co-thermal synthesis with FeCl3. The physicochemical properties, structure, and thermal stability of the complex were analyzed using FE-SEM, SEC-MALLS, FT-IR, XRD, and DSC techniques. Furthermore, the antioxidant activity of the polysaccharide-iron complex was evaluated through an experiment in vitro. The results revealed that the polysaccharide-iron complex had an iron content of 6.1% and an average particle size of 860.4 nm. The microstructure analysis indicated that the polysaccharide-iron complex possessed a flaky morphology with smooth and compact surfaces. Moreover, the formation of the Fe3+ complex did not alter the structural framework of the polysaccharide; instead, it enhanced the polysaccharide's thermal stability. Compared to traditional iron supplements, the E. ulmoides-derived polysaccharide-iron complex demonstrated significant antioxidant activity. Therefore, this novel compound exhibits significant potential as a viable iron supplement.

Enhancing sustainable supply chains through traceability, transparency and stakeholder collaboration: A quantitative analysis

AbstractTraceability and transparency are essential for sustainability in complex global supply chains (SCs), but they remain elusive goals in practice. Scholars and practitioners consistently advocate collaboration amongst SC stakeholders as a means of enhancing them, yet little is known regarding their interrelation and contribution to sustainability. We adopt the SC practice‐based view (SCPV) to propose and test an explanatory model elucidating how to deploy collaboration, traceability and transparency to achieve triple bottom line (TBL) performance within global SCs. Focusing on the paramount example of complex fashion‐apparel SCs, we analyse the insights gained from 139 suppliers—typically ignored in favour of focal firms—using Partial Least Squares Structural Equations Modelling. Our results provide a concrete battery of not‐necessarily complex or inimitable activities empirically proven to help put traceability and transparency into practice to achieve TBL performance. The SCPV approach contends that everyday practices, activities and relationships amongst SC stakeholders underpin TBL performance.

Molecular Mechanisms of Plant Extracts in Protecting Aging Blood Vessels.

Plant Extracts (PE) are natural substances extracted from plants, rich in various bioactive components. Exploring the molecular mechanisms and interactions involved in the vascular protective effects of PE is beneficial for the development of further strategies to protect aging blood vessels. For this review, the content was obtained from scientific databases such as PubMed, China National Knowledge Infrastructure (CNKI), and Google Scholar up to July 2024, using the search terms "Plant extracts", "oxidative stress", "vascular aging", "endothelial dysfunction", "ROS", and "inflammation". This review highlighted the effects of PE in protecting aging blood vessels. Through pathways such as scavenging reactive oxygen species, activating antioxidant signaling pathways, enhancing respiratory chain complex activity, inhibiting mitochondrial-reactive oxygen species generation, improving nitric oxide bioavailability, downregulating the secretion of inflammatory factors, and activating sirtuins 1 and Nrf2 signaling pathways, it can improve vascular structural and functional changes caused by age-related oxidative stress, mitochondrial dysfunction, and inflammation due to aging, thereby reducing the incidence of age-related cardiovascular diseases.

Legionella pneumophila cell surface RtxA release by LapD/LapG and its role in virulence

BackgroundLegionella pneumophila is a Gram-negative intracellular bacillus and is the causative agent of a severe form of pneumonia called Legionnaires’ disease which accounts for 2-9% of cases of community acquired pneumonia. It produces an extremely large protein belonging to the RTX (Repeats in ToXin) family, called RtxA, and we previously reported that RtxA is transported by a dedicated type 1 secretion system (T1SS) to the cell surface. RTX proteins have been shown to participate in the virulence or biofilm formation of various bacteria, the most studied models being the pore forming hemolysin A (HlyA) of Escherichia coli and the biofilm associated protein LapA of P. fluorescens. LapA localization depends on the enzymatic release by LapD/LapG complex activity. This study aimed to elucidate the dual localization (cell surface associated or released state) of L. pneumophila RTX protein (RtxA) and whether this released versus sequestered state of RtxA plays a role in L. pneumophila virulence.ResultsThe hereby work reveals that, in vitro, LapG periplasmic protease cleaves RtxA N-terminus in the middle of a di-alanine motif (position 108–109). Consistently, a strain lacking LapG protease maintains RtxA on the cell surface, whereas a strain lacking the c-di-GMP receptor LapD does not exhibit cell surface RtxA because of its continuous cleavage and release, as in the LapA-D-G model of Pseudomonas fluorescens. Interestingly, our data point out a key role of RtxA in enhancing the infection process of amoeba cells, regardless of its location (embedded or released); therefore, this may be the result of a secondary role of this surface protein.ConclusionsThis is the first experimental identification of the cleavage site within the RTX protein family. The primary role of RtxA in Legionella is still questionable as in many other bacterial species, hence it sounds reasonable to propose a major function in biofilm formation, promoting cell aggregation when RtxA is embedded in the outer membrane and facilitating biofilm dispersion in case of RtxA release. The role of RtxA in enhancing the infection process may be a result of its action on host cells (i.e., PDI interaction or pore-formation), and independently of its status (embedded or released).

Diastolic dysfunction in Alzheimer’s disease model mice is associated with Aβ-amyloid aggregate formation and mitochondrial dysfunction

Alzheimer's Disease (AD) is a progressive neurodegenerative disease caused by the deposition of Aβ aggregates or neurofibrillary tangles. AD patients are primarily diagnosed with the concurrent development of several cardiovascular dysfunctions. While few studies have indicated the presence of intramyocardial Aβ aggregates, none of the studies have performed detailed analyses for pathomechanism of cardiac dysfunction in AD patients. This manuscript used aged APPSWE/PS1 Tg and littermate age-matched wildtype (Wt) mice to characterize cardiac dysfunction and analyze associated pathophysiology. Detailed assessment of cardiac functional parameters demonstrated the development of diastolic dysfunction in APPSWE/PS1 Tg hearts compared to Wt hearts. Muscle function evaluation showed functional impairment (decreased exercise tolerance and muscle strength) in APPSWE/PS1 Tg mice. Biochemical and histochemical analysis revealed Aβ aggregate accumulation in APPSWE/PS1 Tg mice myocardium. APPSWE/PS1 Tg mice hearts also demonstrated histopathological remodeling (increased collagen deposition and myocyte cross-sectional area). Additionally, APPSWE/PS1 Tg hearts showed altered mitochondrial dynamics, reduced antioxidant protein levels, and impaired mitochondrial proteostasis compared to Wt mice. APPSWE/PS1 Tg hearts also developed mitochondrial dysfunction with decreased OXPHOS and PDH protein complex expressions, altered ETC complex dynamics, decreased complex activities, and reduced mitochondrial respiration. Our results indicated that Aβ aggregates in APPSWE/PS1 Tg hearts are associated with defects in mitochondrial respiration and complex activities, which may collectively lead to cardiac diastolic dysfunction and myocardial pathological remodeling.

Cordyceps sinensis ameliorates idiopathic pulmonary fibrosis in mice via inhibiting mitochondrion‐mediated oxidative stress

AbstractIdiopathic pulmonary fibrosis (IPF) represents a chronic interstitial lung disease with an unclear underlying mechanism and currently lacks a definitive treatment. Cordyceps sinensis (CS), renowned for its pharmacological properties in traditional Chinese medicine and extensive use in lung disease treatment, holds promise as a therapeutic agent for IPF. However, the specific role of CS in treating IPF remains unclear. In this study, we aimed to assess the efficacy of CS in treating IPF and unravel potential underlying mechanisms. Our results demonstrate that CS treatment effectively mitigated pulmonary inflammation and collagen deposition in bleomycin‐induced IPF mice. Proteomics analysis revealed that the regulation of mitochondrial oxidative phosphorylation may serve as a potential protective mechanism of CS against IPF in mice. Further investigation unveiled that CS could suppress the excessive production of mitochondrial reactive oxygen species in lung tissues induced by bleomycin through moderating the expression and activity of mitochondrial complexes, thus safeguarding the integrity and function of mitochondria. Overall, our findings not only underscore the effectiveness of CS in preventing bleomycin‐induced IPF but also highlight mitochondrial‐mediated oxidative stress as a promising therapeutic target for treating IPF.

DNA cytosine methyltransferases differentially regulate genome-wide hypermutation and interhomolog recombination in Trichoderma reesei meiosis.

Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type and spo11Δ meiosis. DNA methyltransferases (DNMTs) perform multiple tasks in meiosis. Three DNMT genes (rid1, dim2and dimX) differentially regulate genome-wide cytosine methylation and C:G-to-T:A hypermutations in different chromosomal regions. We have identified two types of DSBs: type I DSBs require spo11 or rid1 for initiation, whereas type II DSBs do not rely on spo11 and rid1 for initiation. rid1 (but not dim2) is essential for Rad51-mediated DSB repair and normal meiosis. rid1 and rad51 exhibit a locus heterogeneity (LH) relationship, in which LH-associated proteins often regulate interconnectivity in protein interaction networks. This LH relationship can be suppressed by deleting dim2 in a haploid rid1Δ (but not rad51Δ) parental strain, indicating that dim2 and rid1 share a redundant function that acts earlier than rad51 during early meiosis. In conclusion, our studies provide the first evidence of the involvement of DNMTs during meiotic initiation and recombination.

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer

Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC. Notably, chemical disruption of mSWI/SNF ATPase activity attenuates proliferation of all POU2F3-positive SCLCs, while disruption of non-canonical BAF (ncBAF) via BRD9 degradation is effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF targets to and maintains accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, clinical-grade pharmacologic disruption of SMARCA4/2 ATPases and BRD9 decreases POU2F3-SCLC tumor growth and increases survival invivo. These results demonstrate mSWI/SNF-mediated governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy for POU2F3-positive SCLCs.

An Integrated Neural Optrode with Modification of Polymer-Carbon Composite Films for Suppression of the Photoelectric Artifacts.

Optogenetics-based integrated photoelectrodes with high spatiotemporal resolution play an important role in studying complex neural activities. However, the photostimulation artifacts caused by the high level of integration and the high impedance of metal recording electrodes still hinder the application of photoelectrodes for optogenetic studies of neural circuits. In this study, a neural optrode fabricated on sapphire GaN material was proposed, and 4 μLEDs and 14 recording microelectrodes were monolithically integrated on a shank. Poly(3,4-ethylenedioxythiophene)/polystyrenesulfonate and multiwalled carbon nanotubes (PEDOT:PSS-MWCNT) and poly(3,4-ethylenedioxythiophene) and graphene oxide (PEDOT-GO) composite films were deposited on the surface of the recording microelectrode by electrochemical deposition. The results demonstrate that compared with the gold microelectrode, the impedances of both composite films reduced by more than 98%, and the noise amplitudes decreased by 70.73 and 87.15%, respectively, when exposed to light stimulation. Adjusting the high and low levels, we further reduced the noise amplitude by 48.3%. These results indicate that modifying the electrode surface by a polymer composite film can effectively enhance the performance of the microelectrode and further promote the application of the optrode in the field of neuroscience.

Synthesis, characterization, and investigation of catalytic properties of RuII complexes with Schiff bases based on 2-hydroxybenzaldehyde and 5-bromo-2-hydroxybenzaldehyde

Pursuing our recent interest concerning the catalytic activity of half-sandwich RuII complexes containing Schiff base ligands (L1 and L2), in this study new Schiff bases and their half-sandwich RuII complexes were prepared. The structures of these compounds were confirmed by a variety of spectral and physical methods such as microanalysis, FT-IR, electronic spectra, proton and carbon NMR, TGA and mass spectra. The catalytic activities of the RuII complexes toward the transfer hydrogenation of ketones to their corresponding alcohols were investigated using i-PrOH as a hydrogen source and solvent. The complexes showed high catalytic activities at catalyst concentrations of 0.01 mmol and were able to carry out transfer hydrogenation (TH) to a wide range of ketones in the presence of KOH. In general, Schiff bases recognition, the coordination chemistry, and the ketone substrates were found to influence the catalytic performance of these complexes.

Disturbance in communication between mitochondrial redox processes and the AMPK/PGC-1α/SIRT-1 axis influences diverse organ symptoms in lupus-affected mice

BackgroundMechanisms behind multiple organ involvement in lupus, is still an enigma for researchers. Mitochondrial dysfunction and oxidative stress are known to be important aspects in lupus etiology however, their role in lupus organ manifestation is yet to be understood. The present study is based on the understanding of interplay between AMPK/PGC-1α/SIRT-1 axis, mitochondrial complexes, and anti-oxidants levels, which might be involved in lupus organ pathology. MethodologyPristane-induced Balb/c mice lupus model (PIL) was utilised and evaluation of anti-oxidants, mitochondrial complexes, pro-inflammatory cytokines levels, biochemical parameters were performed by standard procedures. Tissues were studied by haematoxylin and eosin staining followed by immunohistochemistry. The AMPK/PGC-1α/SIRT-1 expression was analysed by using qPCR and flowcytometry. Analysis of reactive oxygen species (ROS) among WBCs was performed by using various dyes (DCFDA, Mitosox, JC-1) on flowcytometry. ResultSignificant presence of immune complexes (Tissue sections), ANA (Serum), and pro-inflammatory cytokines (plasma), diminished anti-oxidants and altered biochemical parameters depict the altered pathology in PIL which was accompanied by dysregulated mitochondrial complex activity. Differential expression of the AMPK/PGC-1α/SIRT-1 axis was detected in tissue and correlation with mitochondrial and antioxidant activity emerged as negative in PIL group while positive in controls. Close association was observed between ROS, mitochondrial membrane potential, and AMPK/PGC-1α/SIRT-1 axis in WBCs. ConclusionThis study concludes that mitochondria play a dual role in lupus organ pathology, contributing to organ damage while also potentially protecting against damage through the regulation of interactions between antioxidants and the AMPK axis expression.

Acceptors stability modulates the efficiency of post-translational protein N-glycosylation.

N-glycosylation is the most common protein modification in the eukaryotic secretory pathway. It involves the attachment a high mannose glycan to Asn residues in the context of Asn-X-Ser/Thr/Cys, a motif known as N-glycosylation sequon. This process is mediated by STT3A and STT3B, the catalytic subunits of the oligosaccharyltransferase complexes. STT3A forms part of complexes associated with the SEC61 translocon and functions co-translationally. Vacant sequons have another opportunity for glycosylation by complexes carrying STT3B. Local sequence information plays an important role in determining N-glycosylation efficiency, but non-local factors can also have a significant impact. For instance, certain proteins associated with human genetic diseases exhibit abnormal N-glycosylation levels despite having wild-type acceptor sites. Here, we investigated the effect of protein stability on this process. To this end, we generated a family of 40 N-glycan acceptors based on superfolder GFP, and we measured their efficiency in HEK293 cells and in two derived cell lines lacking STT3B or STT3A. Sequon occupancy was highly dependent on protein stability, improving as the thermodynamic stability of the acceptor proteins decreases. This effect is mainly due to the activity of the STT3B-based OST complex. These findings can be integrated into a simple kinetic model that distinguishes local information within sequons from global information of the acceptor proteins.

An AI-Based System Utilizing IoT-Enabled Ambient Sensors and LLMs for Complex Activity Tracking

An AI-Based System Utilizing IoT-Enabled Ambient Sensors and LLMs for Complex Activity Tracking