contact inhibition

Phosphatidylinositol (PI) is the precursor lipid for the minor phosphoinositides (PPIns), which are critical for multiple functions in all eukaryotic cells. It is poorly understood how phosphatidylinositol, which is synthesized in the ER, reaches those membranes where PPIns are formed. Here, we used VT01454, a recently identified inhibitor of class I PI transfer proteins (PITPs), to unravel their roles in lipid metabolism, and solved the structure of inhibitor-bound PITPNA to gain insight into the mode of inhibition...

Neuronal endosomal and lysosomal abnormalities are among the early changes observed in Alzheimer's disease (AD) before plaques appear. However, it is unclear whether distinct endolysosomal defects are temporally organized and how altered γ-secretase function or amyloid precursor protein (APP) metabolism contribute to these changes. Inhibiting γ-secretase chronically, in mouse embryonic fibroblast and hippocampal neurons, led to a gradual endolysosomal collapse initiated by decreased lysosomal calcium and increased cholesterol, causing downstream defects in endosomal recycling and maturation...

UNLABELLED: Fungal phytopathogens cause significant reductions in agricultural yields annually, and overusing chemical fungicides for their control leads to environmental pollution and the emergence of resistant pathogens. Exploring natural isolates with strong antagonistic effects against pathogens can improve our understanding of their ecology and develop new treatments for the future. We isolated and characterized a novel bacterial strain associated with the species Burkholderia cenocepacia , termed APO9, which strongly inhibits Zymoseptoria tritici , a commercially important pathogenic fungus causing Septoria tritici blotch in wheat...

Sludge biochar loaded with Fe-Mn oxides (FMBC) was prepared and employed to remove Cr(vi) from wastewater. The influences of solution pH, co-existing ion, contact time, adsorption temperature and Cd(vi) concentrations on removing Cr(vi) by FMBC were investigated. The Cr(vi) adsorption on FMBC had strong pH dependence. Additionally, Na+ , Mg2+ , Ca2+ , SiO3 2- , NO3 - and Cl- ions exhibited no influence on Cr(vi) removal efficiency for FMBC, whereas there were inhibition effects of Pb2+ , Cu2+ , Ni2+ , CO3 2- , SO4 2- , and PO4 3- on removing Cr(vi)...

Blood-contacting medical devices often succumb to thrombosis, limiting their durability and safety in clinical applications. Thrombosis is fundamentally initiated by the nonspecific adsorption of proteins to the material surface, which is strongly governed by thermodynamic factors established by the nature of the interaction between the material surface, surrounding water molecules, and the protein itself. Along these lines, different surface materials (such as polymeric, metallic, ceramic, or composite) induce different entropic and enthalpic changes at the surface-protein interface, with material wettability significantly impacting this behavior...

The aggregation of transactive response deoxyribonucleic acid (DNA) binding protein of 43 kDa (TDP-43) into ubiquitin-positive inclusions is closely associated with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and chronic traumatic encephalopathy. The 370-375 fragment of TDP-43 (370 GNNSYS375 , TDP-43370-375 ), the amyloidogenic hexapeptides, can be prone to forming pathogenic amyloid fibrils with the characteristic of steric zippers. Previous experiments reported the ALS-associated mutation, serine 375 substituted by glycine (S375G) is linked to early onset disease and protein aggregation of TDP-43...

Poly(ethylene furanoate) (PEF)-based nanocomposites were fabricated with silver (Ag) and titanium dioxide (TiO2 ) nanoparticles by the in-situ polymerization method. The importance of this research work is to extend the usage of PEF-based nanocomposites with improved material properties. The PEF-Ag and PEF-TiO2 nanocomposites showed a significant improvement in color concentration, as determined by the color colorimeter. Scanning electron microscopy (SEM) photographs revealed the appearance of small aggregates on the surface of nanocomposites...

SARS-CoV-2 is the virus responsible for a respiratory disease called COVID-19 that devastated global public health. Since 2020, there has been an intense effort by the scientific community to develop safe and effective prophylactic and therapeutic agents against this disease. In this context, peptides have emerged as an alternative for inhibiting the causative agent. However, designing peptides that bind efficiently is still an open challenge. Here, we show an algorithm for peptide engineering. Our strategy consists of starting with a peptide whose structure is similar to the interaction region of the human ACE2 protein with the SPIKE protein, which is important for SARS-COV-2 infection...

In this study, the α-glucosidase (maltase-glucoamylase: MGAM) and α-amylase inhibitory properties elicited by xylooligosaccharides (XOSs) prepared from dulse xylan were analysed as a potential mechanism to control postprandial hyperglycaemia for type-2 diabetes prevention and treatment. Xylan was purified from red alga dulse powder and used for enzymatic hydrolysis using Sucrase X to produce XOSs. Fractionation of XOSs produced xylobiose (X2), β-(1→3)-xylosyl xylobiose (DX3), xylotriose (X3), β-(1→3)-xylosyl-xylotriose (DX4), and a dulse XOS mixture with n ≥ 4 xylose units (DXM)...

Shale hydration dispersion and swelling are primary causes of wellbore instability in oil and gas reservoir exploration. In this study, inulin, a fructo-oligosaccharide extracted from Jerusalem artichoke roots, was modified by acylation with three acyl chlorides, and the products (C10-, C12-, and C14-inulin) were investigated for their use as novel shale hydration inhibitors. The inhibition properties were evaluated through the shale cuttings hot-rolling dispersion test, the sodium-based bentonite hydration test, and capillary suction...

Currently, the application of solvent exchange-induced in situ gel is underway for drug delivery to the body target site. Nitrocellulose was attempted in this research as the matrix-forming agent in solvent exchange-induced in situ gel for acne and periodontitis treatments. The gel incorporated a combination of 1% w / w levofloxacin HCl and 2% w / w salicylic acid as the active compounds. In order to facilitate formulation development, the study explored the matrix-forming behavior of different concentrations of nitrocellulose in N -methyl pyrrolidone (NMP)...

The hydrophilic and low mechanical properties limited the application of starch-based films. In this work, a hydrophobic starch-based nanofiber mat was first successfully prepared from aqueous solution at room temperature by using electrospinning and glutaraldehyde (GTA) vapor phase crosslinking techniques for active packaging applications. Catechin (CAT) was immobilized in the nanofibers by electrospinning, resulting in higher thermal stability (Tdmax  = 315.23 °C), antioxidant (DPPH scavenging activity = 94...

Fine dust concentrations come in direct contact with the human respiratory system, thereby reducing lung function and causing respiratory diseases such as asthma and rhinitis. The aim of this study was to evaluate the efficacy of GHX02 (combination of four herbs [ Trichosanthes kirilowii, Prunus armeniaca, Coptis japonica , and Scutellaria baicalensis ]), a herbal extract with established efficacy against bronchitis and pulmonary disease, in the treatment of asthma accompanied by rhinitis aggravated by fine dust...

In healthcare facilities, infections caused by Staphylococcus aureus ( S. aureus ) from textile materials are a cause for concern, and nanomaterials are one of the solutions; however, their impact on safety and biocompatibility with the human body must not be neglected. This study aimed to develop a novel multilayer coating with poly(allylamine hydrochloride) (PAH) and immobilized ZnO nanoparticles (ZnO NPs) to make efficient antibacterial and biocompatible cotton, polyester, and nylon textiles. For this purpose, the coated textiles were characterized with profilometry, contact angles, and electrokinetic analyzer measurements...

In this study, the efficacy of the essential oil of Mentha longifolia, Achillea arabica and Artemisia absinthium plants were evaluated against important soil-borne fungal pathogens as Verticillium dahliae, Rhizoctonia solani, and Fusarium oxysporum. Essential oils were obtained from plants by hydrodistillation method and the chemical components of essential oils were determined by analyzing by gas chromatography-mass spectrometry. The main components found as piperitone oxide (13.61%), piperitenone oxide (15...

Long interspersed element-1 (LINE-1 or L1) comprises 17% of the human genome, continuously generates genetic variations, and causes disease in certain cases. However, the regulation and function of L1 remain poorly understood. Here, we uncover that L1 can enrich RNA polymerase IIs (RNA Pol IIs), express L1 chimeric transcripts, and create contact domain boundaries in human cells. This impact of L1 is restricted by a nuclear matrix protein scaffold attachment factor B (SAFB) that recognizes transcriptionally active L1s by binding L1 transcripts to inhibit RNA Pol II enrichment...

Aim This study involves synthesizing metal nanoparticles (NPs) via the green synthesis method using Millettia pinnata leaf, Acacia auriculiformis bark, and Citrus sinensis peel and comparatively evaluating their antibacterial activity in vitro through the analysis of cobalt oxide NPs (CoNPs), copper NPs (CuNPs), and selenium NPs (SeNPs). This research contributes to eco-friendly approaches for producing functional nanomaterials with potential applications in medicine and environmental remediation. Materials and methods The metal NPs were synthesized using M...

DNA methyltransferases DNMT3A- and DNMT3B-mediated DNA methylation critically regulate epigenomic and transcriptomic patterning during development. The hotspot DNMT3A mutations at the site of Arg822 (R882) promote polymerization, leading to aberrant DNA methylation that may contribute to the pathogenesis of acute myeloid leukemia (AML). However, the molecular basis underlying the mutation-induced functional misregulation of DNMT3A remains unclear. Here, we report the crystal structures of the DNMT3A methyltransferase domain, revealing a molecular basis for its oligomerization behavior distinct to DNMT3B, and the enhanced intermolecular contacts caused by the R882H or R882C mutation...

Androgen receptor (AR) is known to play a crucial role in the development and progression of prostate cancer, and compounds that inhibit its activity are regarded as promising for the development of drugs to treat the disease. This study aimed to investigate the AR-inhibiting potential of Citrullus lanatus fruit compounds for prostate cancer drug development. Following HPLC identification, the binding energies, molecular interactions, and pharmacological potentials of the compounds against AR were elucidated using in silico techniques such as, molecular docking, induced-fit docking, molecular dynamics simulation, and ADMET prediction...

Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine (4) . The novel conjugates 6 (a-o) were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy...