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Wyniki wyszukiwania dla: BRCA1 GENE MUTATIONS
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Graphene Production and Biomedical Applications: A Review
PublikacjaGraphene is a two-dimensional nanomaterial composed of carbon atoms with sp2 hybrid orbitals. Both graphene and graphene-based composite have gained broad interest among researchers because of their outstanding physiochemical, mechanical, and biological properties. Graphene production techniques are divided into top-down and bottom-up synthesis methods, of which chemical vapor deposition (CVD) is the most popular. The biomedical...
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Jerzy H. Czembor Prof. dr hab.
OsobyYear of birth: 1965, Poland, Work address: Plant Breeding and Acclimatization Institute –National research Institute (IHAR-PIB), Radzikow, 05-870 Blonie, Poland. Scientific disciplines: agricultural sciences, plant pathology, plant physiology, genetics. Specialization: phytopathology, mycology, plant genetics, molecular genetics, plant breeding, breeding for disease resistance, biotechnology, evaluation of genetic resources,...
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Anticancer imidazoacridinone C-1311 inhibits hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiogenesis
PublikacjaAntitumor imidazoacridinone C-1311 is a DNA-reactive topoisomerase II and FLT3 receptor tyrosine kinase inhibitor. Here, we demonstrate the mechanism of C-1311 inhibitory action on novel targets: hypoxia-inducible factor-1α (HIF-1α), vascular-endothelial growth factor (VEGF), and angiogenesis. In a cell-free system, C-1311 prevented HIF-1α binding to an oligonucleotide encompassing a canonical hypoxia-responsive element (HRE),...
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Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife
PublikacjaA study of 269 children enrolled into a National Registry for children with persistent glomerular hematuria identified 131 individuals with genetically confirmed X-linked Alport Syndrome. A single variant c.1871G>A p.Gly624Asp (G624D) in COL4A5 was predominant and accounted for 39% of Xlinked Alport Syndrome in unrelated Polish families (44 of 113). To evaluate its origins, the genetic variation in a 2.79 Mb segment encompassing...
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Enhanced susceptibility of SARS-CoV-2 spike RBD protein assay targeted by cellular receptors ACE2 and CD147: Multivariate data analysis of multisine impedimetric response
PublikacjaSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of spike protein to the host cell surface-expressing angiotensin-converting enzyme 2 (ACE2) or by endocytosis mediated by extracellular matrix metalloproteinase inducer (CD147). We present extended statistical studies of the multisine dynamic electrochemical impedance spectroscopy (DEIS) revealing interactions between Spike RBD and...
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Catalytic Mechanism of Non-Target DNA Cleavage in CRISPR-Cas9 Revealed by Ab Initio Molecular Dynamics
PublikacjaCRISPR-Cas9 is a cutting-edge genome editing technology, which uses the endonuclease Cas9 to introduce mutations at desired sites of the genome. This revolutionary tool is promising to treat a myriad of human genetic diseases. Nevertheless, the molecular basis of DNA cleavage, which is a fundamental step for genome editing, has not been established. Here, quantum–classical molecular dynamics (MD) and free energy methods are used...
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Comparing Phylogenetic Trees by Matching Nodes Using the Transfer Distance Between Partitions
PublikacjaAbility to quantify dissimilarity of different phylogenetic trees describing the relationship between the same group of taxa is required in various types of phylogenetic studies. For example, such metrics are used to assess the quality of phylogeny construction methods, to define optimization criteria in supertree building algorithms, or to find horizontal gene transfer (HGT) events. Among the set of metrics described so far in...
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Fusion of DNA-binding domain of Pyrococcus furiosus ligase with TaqStoffel DNA polymerase as a useful tool in PCR with difficult targets
PublikacjaThe DNA coding sequence of TaqStoffel polymer- ase was fused with the DNA-binding domain of Pyrococcus furiosus ligase. The resulting novel recombinant gene was cloned and expressed in E. coli. The recombinant enzyme was purified and its enzymatic features were studied. The fusion protein (PfuDBDlig-TaqS) was found to have enhanced processivity as a result of the conversion of the Taq DNA polymerase from a relatively low processive...
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Triazoloacridone C-1305 impairs XBP1 splicing by acting as a potential IRE1α endoribonuclease inhibitor
PublikacjaInositol requiring enzyme 1 alpha (IRE1α) is one of three signaling sensors in the unfolding protein response (UPR) that alleviates endoplasmic reticulum (ER) stress in cells and functions to promote cell survival. During conditions of irrevocable stress, proapoptotic gene expression is induced to promote cell death. One of the three signaling stressors, IRE1α is an serine/threonine-protein kinase/endoribonuclease (RNase) that...
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Polylysine for Skin Regeneration: A Review of Recent Advances and Perspectives
PublikacjaThere have been several attempts to find promising biomaterials for skin regeneration, among which polylysine (a homopolypeptide) has shown benefits in the regeneration and treatment of skin disorders. This class of biomaterials has shown exceptional abilities due to their macromolecular structure. Polylysine-based biomaterials can not only be used as tissue engineering scaffolds for skin regeneration, but also as drug carriers...
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HDAC Inhibitors: Innovative Strategies for Their Design and Applications
PublikacjaHistone deacetylases (HDACs) are a large family of epigenetic metalloenzymes that are involved in gene transcription and regulation, cell proliferation, differentiation, migration, and death, as well as angiogenesis. Particularly, disorders of the HDACs expression are linked to the development of many types of cancer and neurodegenerative diseases, making them interesting molecular targets for the design of new efficient drugs...
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Karaś P., Kochanowicz K., Pitek M., Domański P., Obuchowski I., Tomiczek B., Liberek K.: Evolution towards simplicity in bacterial small heat shock protein system// eLife -, (2023), s.1-21
PublikacjaEvolution can tinker with multi-protein machines and replace them with simpler single-protein systems performing equivalent functions in an equally efficient manner. It is unclear how, on a molecular level, such simplification can arise. With ancestral reconstruction and biochemical analysis, we have traced the evolution of bacterial small heat shock proteins (sHsp), which help to refold proteins from aggregates using either...
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Evolution towards simplicity in bacterial small heat shock protein system
PublikacjaEvolution can tinker with multi-protein machines and replace them with simpler single-protein systems performing equivalent functions in an equally efficient manner. It is unclear how, on a molecular level, such simplification can arise. With ancestral reconstruction and biochemical analysis, we have traced the evolution of bacterial small heat shock proteins (sHsp), which help to refold proteins from aggregates using either two...
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Sequence-dependent structural properties of B-DNA: what have we learned in 40 years?
PublikacjaThe structure of B-DNA, the physiological form of the DNA molecule, has been a central topic in biology, chemistry and physics. Far from uniform and rigid, the double helix was revealed as a flexible and structurally polymorphic molecule. Conformational changes that lead to local and global changes in the helix geometry are mediated by a complex choreography of base and backbone rearrangements affecting the ability of the B-DNA...
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Poloxamer: A versatile tri-block copolymer for biomedical applications
PublikacjaPoloxamers, also called Pluronic, belong to a unique class of synthetic tri-block copolymers containing central hydrophobic chains of poly(propylene oxide) sandwiched between two hydrophilic chains of poly(ethylene oxide). Some chemical characteristics of poloxamers such as temperature-dependent self-assembly and thermo-reversible behavior along with biocompatibility and physiochemical properties make poloxamer-based biomaterials...
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Drug-resistant and hospital-associated Enterococcus faecium from wastewater, riverine estuary and anthropogenically impacted marine catchment basin.
PublikacjaEnterococci, ubiquitous colonizers of humans and other animals, play an increasingly important role in health-care associated infections (HAIs). Acquisition of resistance determinants not only seriously limits available therapeutic options but also increases available gene pool for other species. It is believed that the recent evolution of two clinically relevant species, Enterococcus faecalis and Enterococcus faecium occurred...
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Phylogenetic trees of genus Oncidium Sw. based on analysis of DNA sequences
Dane BadawczeGenus Oncidium Sw. is widely regarded as a polyphiletic, and the taxonomic boundaries between him and such genera as Odontoglossum Kunth. or Miltonia Lindley remain blurred. The goal of the study was to determine the phylogenetic relationships within the genus Oncidium s.lato based on the DNA sequences analysis. The correlation between molecular data...
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Molecularly targeted nanoparticles: an emerging tool for evaluation of expression of the receptor for advanced glycation end products in a murine model of peripheral artery disease
PublikacjaAbstract Background: Molecular imaging with molecularly targeted probes is a powerful tool for studying the spatio-temporal interactions between complex biological processes. The pivotal role of the receptor for advanced glycation end products (RAGE) in numerous pathological processes, aroused the demand for RAGE targeted imaging in various diseases. In the study, we evaluated the use of a diagnostic imaging agent for RAGE quantification...
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Reverse vaccinology-based prediction of a multi-epitope SARS-CoV-2 vaccine and its tailoring to new coronavirus variants
PublikacjaThe genome feature of SARS-CoV-2 leads the virus to mutate and creates new variants of concern. Tackling viral mutations is also an important challenge for the development of a new vaccine. Accordingly, in the present study, we undertook to identify B- and T-cell epitopes with immunogenic potential for eliciting responses to SARS-CoV-2, using computational approaches and its tailoring to coronavirus variants. A total of 47 novel...
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c-Myc inhibition and p21 modulation contribute to unsymmetrical bisacridines-induced apoptosis and senescence in pancreatic cancer cells
PublikacjaBackground Pancreatic cancer (PC) is one of the most aggressive cancers and is the seventh leading cause of cancer-related death worldwide. PC is characterized by rapid progression and resistance to conventional treatments. Mutations in KRAS, CDKN2A, TP53, SMAD4/DPC4, and MYC are major genetic alterations associated with poor treatment outcomes in patients with PC. Therefore, optimizing PC therapy is a tremendous challenge. Unsymmetrical...
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Pathogenesis of psoriasis in the “omic” era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis
PublikacjaPsoriasis is a systemic disease that is strictly connected with metabolic disorders (insulin resistance, atherogenic dyslipidemia, arterial hypertension, and cardiovascular diseases). It occurs more often in patients with a more severe course of the disease. Obesity is specially an independent risk factor and it is associated with a worse treatment outcome because of the high inflammatory activity of visceral fatty tissue and...
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Why Are Left-Handed G-Quadruplexes Scarce?
PublikacjaG-quadruplexes (G4s) are nucleic acid structures crucial for the regulation of gene expression and genome maintenance. While they hold promise as nanodevice components, achieving desired G4 folds requires understanding the interplay between stability and structural properties, like helicity. Although right-handed G4 structures dominate the experimental data, the molecular basis for this preference over left-handed helicity is unclear....
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Customizing nano-chitosan for sustainable drug delivery
PublikacjaChitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, various...
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PCR and real-time PCR assays to detect fungi of Alternaria alternata species
PublikacjaFungi of the Alternaria genus are mostly associated with allergic diseases. However, with a growing number of immunocompromised patients, these fungi, with A. alternata being the most prevalent one, are increasingly recognized as etiological agents of infections (phaeohyphomycoses) in humans. Nowadays, identification of Alternaria spp. requires their pure culture and is solely based on morphological criteria. Clinically, Alternaria...
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Molecular dynamics simulations reveal the balance of forces governing the formation of a guanine tetrad—a common structural unit of G-quadruplex DNA
PublikacjaG-quadruplexes (G4) are nucleic acid conformations of guanine-rich sequences, in which guanines are arranged in the square-planar G-tetrads, stacked on one another. G4 motifs form in vivo and are implicated in regulation of such processes as gene expression and chromosome maintenance. The structure and stability of various G4 topologies were determined experimentally; however, the driving forces for their formation are not fully...
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Small regulatory bacterial RNAs regulating the envelope stress response
PublikacjaMost bacteria encode a large repertoire of RNA-based regulatory mechanisms. Recent discoveries have revealed that the expression of many genes is controlled by a plethora of base-pairing noncoding small regulatory RNAs (sRNAs), regulatory RNA-binding proteins and RNA-degrading enzymes. Some of these RNA-based regulated processes respond to stress conditions and are involved in the maintenance of cellular homeostasis. They achieve...
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Specific detection of Alternaria alternata by PCR and real-time PCR
PublikacjaFungi of Alternaria genus are cosmopolitan organisms, which spores can be found in the air, soil, water, clothing and food. They commonly occur as saprotrophs on the plant remains, contributing to the decomposition of organic matter. Additionally, they are components of the normal human and animal skin flora. Alternaria spp. are also known human allergens, causing hay fever and allergic reactions that can lead to the development...
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Molecular basis of lipopolysaccharide heterogeneity in Escherichia coli: envelope stress-responsive regulators control the incorporation of glycoforms with a third 3-deoxy-α-D-manno-oct-2-ulosonic acid and rhamnose.
PublikacjaMass spectrometric analyses of lipopolysaccharide (LPS) from isogenic Escherichia coli strains with nonpolar mutations in the waa locus or overexpression of their cognate genes revealed that waaZ and waaS are the structural genes required for the incorporation of the third 3-deoxy-α-D-manno-oct-2-ulosonic acid (Kdo) linked to Kdo disaccharide and rhamnose, respectively. The incorporation of rhamnose requires prior sequential incorporation...
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Structure of solvation water around the active and inactive regions of a type III antifreeze protein and its mutants of lowered activity
PublikacjaWater molecules from the solvation shell of the ice-binding surface are considered important for the antifreeze proteins to perform their function properly. Herein, we discuss the problem whether the extent of changes of the mean properties of solvation water can be connected with the antifreeze activity of the protein. To this aim, the structure of solvation water of a type III antifreeze protein from Macrozoarces americanus (eel...
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Chemical Aspects of Biological Activity of Isothiocyanates and Indoles, the Products of Glucosinolate Decomposition
PublikacjaThere is growing evidence that cancer chemoprevention employing natural, bioactive compounds may halt or at least slow down the different stages of carcinogenesis. A particularly advantageous effect is attributed to derivatives of sulfur-organic phytochemicals, such as glucosinolates (GLs) synthesized mainly in Brassicaceae plant family. GLs are hydrolysed enzymatically to bioactive isothiocyanates (ITC) and indoles, which exhibit strong...
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DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
PublikacjaThe human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization...
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Carbon Nanomaterials in Seed Priming: Current Possibilities
PublikacjaThe prevailing agricultural system has become deeply ingrained and insufficient due to outdated practices inherited from the Green Revolution, necessitating innovative approaches for sustainable agricultural development. Nanomaterials possess the potential to significantly improve the efficient utilization of resources while simultaneously encouraging sustainability. Among these, carbonaceous nanomaterials have found diverse applications...
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The New Klebsiella pneumoniae ST152 Variants with Hypermucoviscous Phenotype Isolated from Renal Transplant Recipients with Asymptomatic Bacteriuria-Genetic Characteristics by WGS.
PublikacjaKlebsiella pneumoniae (Kp) is one of the most important etiological factors of urinary tract infections in renal transplant (RTx) recipients. We described the antimicrobial susceptibility phenotypes and genomic features of two hypermucoviscous (HM) Kp isolates recovered from RTx recipients with asymptomatic bacteriuria (ABU). Using whole genome sequencing (WGS) data, we showed that the strains belong to the ST152 lineage with the...
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Tailor-Made Polysaccharides for Biomedical Applications
PublikacjaPolysaccharides (PSAs) are carbohydrate-based macromolecules widely used in the biomedical field, either in their pure form or in blends/nanocomposites with other materials. The relationship between structure, properties, and functions has inspired scientists to design multifunctional PSAs for various biomedical applications by incorporating unique molecular structures and targeted bulk properties. Multiple strategies, such as...
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Interactions between polyphenolic antioxidants quercetin and naringenin dictate the distinctive redox-related chemical and biological behaviour of their mixtures
PublikacjaFood synergy concept is suggested to explain observations that isolated antioxidants are less bioactive than real foods containing them. However, mechanisms behind this discrepancy were hardly studied. Here, we demonstrate the profound impact of interactions between two common food flavonoids (individual: aglycones quercetin—Q and naringenin—N− or their glycosides rutin—R and naringin—N+ vs. mixed: QN− and RN+) on their electrochemical...
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Changes in Epigenetic Patterns Related to DNA Replication in Vicia faba Root Meristem Cells under Cadmium-Induced Stress Conditions
PublikacjaExperiments on Vicia faba root meristem cells exposed to 150 µM cadmium chloride (CdCl2) were undertaken to analyse epigenetic changes, mainly with respect to DNA replication stress. Histone modifications examined by means of immunofluorescence labeling included: (1) acetylation of histone H3 on lysine 56 (H3K56Ac), involved in transcription, S phase, and response to DNA damage during DNA biosynthesis; (2) dimethylation of histone...
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Identification and properties of the psychrophilic bacterium Desulfolatea psychrophila single-stranded DNA binding proteins
PublikacjaTo study the biochemical properties of SSB from Desulfolatea psychrophila (DpsSSB), we have cloned the ssb genes obtained by PCR and have developed Escherichia coli overexpression systems. The gene consists of an open reading frame of 426 nucleotides encoding SSB protein of 142 amino acids with a calculated molecular mass of 15.6 kDa and it is the smallest known bacterial SSB protein indentified to date. The amino-acid sequence...
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Why do G-quadruplexes dimerize through the 5’-ends? Driving forces for G4 DNA dimerization examined in atomic detail
PublikacjaG-quadruplexes (G4) are secondary structures formed by guanine-rich nucleic acid sequences and shown to exist in living cells where they participate in regulation of gene expression and chromosome maintenance. G-quadruplexes with solvent-exposed guanine tetrads show the tendency to associate together through cofacial stacking, which may be important for packaging of G4-forming sequences and allows for the design of higher-order...
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Antibiotic resistance and prevalence of class 1 and 2 integrons in Escherichia coli isolated from two wastewater treatment plants, and their receiving waters (Gulf of Gdansk, Baltic Sea, Poland)
PublikacjaIn this study, antimicrobial-resistance patterns were analyzed in Escherichia coli isolates from raw (RW) and treated wastewater (TW) of two wastewater treatment plants (WWTPs), their marine outfalls (MOut), and mouth of the Vistula River (VR). Susceptibility of E. coli was tested against different classes of antibiotics. Isolates resistant to at least one antimicrobial agent were PCR tested for the presence of integrons. Ampicillin-resistant...
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A new assay for the simultaneous identification and differentiation of Klebsiella oxytoca strains.
PublikacjaKlebsiella oxytoca is the second most frequently identified species of Klebsiella isolated from hospitalized patients. Klebsiella spp. is difficult to identify using conventional methods and is often misclassified in clinical microbiology laboratories. K. oxytoca is responsible for an increasing number of multi-resistant infections in hospitals because of insufficient detection and identification. In this study, we propose a new...
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Examination of epigenetic inhibitor zebularine in treatment of skin wounds in healthy and diabetic mice
PublikacjaDNA methyltransferase inhibitor zebularine was proven to induce regeneration in the ear pinna in mice. We utilized a dorsal skin wound model to further evaluate this epigenetic inhibitor in wound healing. Full-thickness excisional wounds were made on the dorsum of 2 and 10-month-old healthy BALB/c and 3 and 8-month-old diabetic (db/db) mice, followed by topical or intraperitoneal zebularine delivery. Depending on the strain, age,...
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Immobilization on magnetic nanoparticles of therecombinant trehalose synthase from Deinococcusgeothermalis
PublikacjatIn our study the gene encoding trehalose synthase from Deinococcus geothermalis was cloned and overexpressed inEscherichia coli Rosetta (DE3)pLysS. Wild-type trehalose synthase has been purified from host protein after cell dis-ruption and precipitation at 20% ammonium sulphate saturation. Recombinant trehalose synthase was immobilizedonto glutaraldehyde activated silanized magnetic ferrous-ferric oxide by using covalent binding...
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Identification of Substrates of Cytoplasmic Peptidyl-Prolyl Cis/Trans Isomerases and Their Collective Essentiality in Escherichia Coli
PublikacjaProtein folding often requires molecular chaperones and folding catalysts, such as peptidyl-prolyl cis/trans isomerases (PPIs). The Escherichia coli cytoplasm contains six well-known PPIs, although a requirement of their PPIase activity, the identity of their substrates and relative enzymatic contribution is unknown. Thus, strains lacking all periplasmic and one of the cytoplasmic PPIs were constructed. Measurement of their PPIase...
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Sex contribution to average age at onset of Huntington's disease depends on the number of (CAG)n repeats
PublikacjaHuntington’s disease (HD) is a hereditary neurodegenerative disorder caused by the extension of the CAG repeats in exon 1 of the HTT gene and is transmitted in a dominant manner. The present study aimed to assess whether patients’ sex, in the context of mutated and normal allele length, contributes to age on onset (AO) of HD. The study population comprised a large cohort of 3723 HD patients from the European Huntington’s Disease...
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In Silico Safety Assessment of Bacillus Isolated from Polish Bee Pollen and Bee Bread as Novel Probiotic Candidates
PublikacjaBacillus species isolated from Polish bee pollen (BP) and bee bread (BB) were characterized for in silico probiotic and safety attributes. A probiogenomics approach was used, and in-depth genomic analysis was performed using a wide array of bioinformatics tools to investigate the presence of virulence and antibiotic resistance properties, mobile genetic elements, and secondary metabolites. Functional annotation and Carbohydrate-Active...
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Suspended-sediment transport related to ice-cover conditions during cold and warm winters, Toudaoguai stretch of the Yellow River, Inner Mongolia, China
PublikacjaThe presence of winter ice in cold regions changes the water level, flow rate, velocity distribution, and other parameters of the river, which in turn affects the sediment concentration and channel evolution. Based on data obtained from Toudaoguai Hydrological Station from 1959 to 2021, this study examines the characteristics of the ice regime during cold and warm winters and the water and sediment transport processes along the...
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imPlatelet classifier: image‐converted RNA biomarker profiles enable blood‐based cancer diagnostics
PublikacjaLiquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia...
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Thermodynamics aspects of interactions between acridine derivatives and DNA
PublikacjaDNA is a molecular target for many anticancer and antiviral drugs. Therefore, a clear understanding of the interaction of small molecules with DNA is important in the rational design of ligands that can bind to DNA with high affinity and selectivity. There are several methods to investigate interactions between drug and DNA. Some of them measure changing into DNA structures, such as lengthening and untwisting of helix of DNA. Other...
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Teratomas of Drosera capensis var. alba as a source of naphthoquinone: ramentaceone
PublikacjaPlants belonging to genus Drosera (family Droseraceae) contain pharmacologically active naphthoquinones such as ramentaceone and plumbagin. Hairy root cultures obtained following Agrobacterium rhizogenes-mediated transformation have been reported to produce elevated levels of secondary compounds as well as exhibit desirable rapid biomass accumulation in comparison to untransformed plants. The aim of this study was to establish...
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The treatment of wastewater containing pharmaceuticals in microcosm constructed wetlands: the occurrence of integrons (int1–2) and associated resistance genes (sul1–3, qacEΔ1)
PublikacjaThe aim of this study was to analyze the occurrence of sulfonamide resistance genes (sul1–3) and other genetic elements as antiseptic resistance gene (qacEΔ1) and class 1 and class 2 integrons (int1–2) in the upper layer of substrate and in the effluent of microcosm constructed wetlands (CWs) treating artificial wastewater containing diclofenac and sulfamethoxazole (SMX), which is a sulfonamide antibiotic. The bacteria in the substrate...