• Ulrich Stevenson opublikował 1 rok, 3 miesiące temu

    Together, we conclude that the fungal-like particles and the conditioned medium elicit an inflammatory response in adipocytes through the canonical or classical NF-κB pathway.Bioengineered nanoconjugates have enormous potential as a multifunctional platform for biomedical applications. Conjugation between biotic and abiotic materials enables formulation of nanoconjugates with enhanced physico-chemical properties, increased stability and ability to overcome the inherent shortcomings of individual materials. In this study, we report the preparation and biophysical characterization of an antibacterial system formulated by functionalizing reduced graphene oxide (rGO) with an antimicrobial peptide via covalent as well as non-covalent interaction mechanisms. Environmentally benign synthesis approach was adopted for the formation of rGO, using L-ascorbic acid as a reducing agent. Covalently conjugated peptide-graphitic conjugate displayed improved antibacterial efficacy against Escherichia coli with considerably low cytotoxic activity towards erythrocytes in comparison to self-assembled conjugate and rGO alone. The studies described herein are highly significant in the field of biomaterials and aims to open new avenues of research focusing on a plethora of applications as a prospective non-toxic substitute to conventional antibacterial approaches.The aim of the study was to analyze the long-term outcome (>20 years) after treatment of posterior fossa medulloblastoma (MB) in childhood. We analyzed data from patients treated for posterior fossa MB between 1974 (introduction of the first international treatment protocol in Norway) and 1987 (when use of radiotherapy was abandoned in children under 4 years of age). Out of 47 children, 24 survived >20 years. At the time of analysis, 16 patients (median age 41 years, range 32-52) were alive (median follow-up 34 years, range 30-42), while 8 patients died 22-41 years (median 31 years) after primary treatment one late death (after 22 years) was due to tumor recurrence whilst other 7 deaths (after 23 to 41 years) were related to the detrimental effects of the treatment (secondary tumors, stroke, severe epilepsy and depression). Observed 20- and 30-year survival rates were 51% and 44%, respectively. Despite successful treatment of MB in childhood and satisfactory tumor control during the first 20 years following primary treatment, our data indicates that even long-term survivors may die from tumor recurrence. However, the main factors causing late mortality and morbidity in long-term survivors seem to be the complications related to radiotherapy given in childhood.Selection rules are of vital importance in determining the basic optical properties of atoms, molecules and semiconductors. They provide general insights into the symmetry of the system and the nature of relevant electronic states. A two-dimensional electron gas in a magnetic field is a model system where optical transitions between Landau levels (LLs) are described by simple selection rules associated with the LL index N. Here we examine the inter-LL optical transitions of high-quality bilayer graphene by photocurrent spectroscopy measurement. We observed valley-dependent optical transitions that violate the conventional selection rules Δ|N| = ± 1. Moreover, we can tune the relative oscillator strength by tuning the bilayer graphene bandgap. Our findings provide insights into the interplay between magnetic field, band structure and many-body interactions in tunable semiconductor systems, and the experimental technique can be generalized to study symmetry-broken states and low energy magneto-optical properties of other nano and quantum materials.In Alzheimer’s disease (AD) amyloid-β (Aβ) deposits may cause impairments in choroid plexus, a specialised brain structure which forms the blood-cerebrospinal fluid (CSF) barrier. We previously carried out a mass proteomic-based study in choroid plexus from AD patients and we found several differentially regulated proteins compared with healthy subjects. One of these proteins, annexin A5, was previously demonstrated implicated in blocking Aβ-induced cytotoxicity in neuronal cell cultures. Here, we investigated the effects of annexin A5 on Aβ toxicity in choroid plexus. We used choroid plexus tissue samples and CSF from mild cognitive impairment (MCI) and AD patients to analyse Aβ accumulation, cell death and annexin A5 levels compared with control subjects. Choroid plexus cell cultures from rats were used to analyse annexin A5 effects on Aβ-induced cytotoxicity. AD choroid plexus exhibited progressive reduction of annexin A5 levels along with progressive increased Aβ accumulation and cell death as disease stage was higher. On the other hand, annexin A5 levels in CSF from patients were found progressively increased as the disease stage increased in severity. In choroid plexus primary cultures, Aβ administration reduced endogenous annexin A5 levels in a time-course dependent manner and simultaneously increased annexin A5 levels in extracellular medium. Annexin A5 addition to choroid plexus cell cultures restored the Aβ-induced impairments on autophagy flux and apoptosis in a calcium-dependent manner. We propose that annexin A5 would exert a protective role in choroid plexus and this protection is lost as Aβ accumulates with the disease progression. Then, brain protection against further toxic insults would be jeopardised.Most of the knowledge about genetic variants at the sequence level in cattle is for Bos primigenius taurus populations. Here, we presented a complete genomic characterization of 52 Nellore (Bos primigenius indicus) bulls, revealing specific zebu DNA variants with putative impact in tropical adaptation and productive traits. Single nucleotide polymorphisms (SNPs) and insertion/deletion (INDELs) mutations were identified using the newest bovine reference genome ARS_UCD1.2, and variant functional consequences were predicted using the Ensembl VEP software. A total of 35,753,707 SNPs and 4,492,636 INDELs were detected and annotated to their functional effects. We identified 400 genes that comprised both, a SNP and an INDEL, of high functional impact on proteins (i.e. variants that cause protein truncation, loss of function or triggering nonsense-mediated decay). Among these, we highlight the following genes BoLA, associated with cattle immune response to infections and reproduction aspects; HSPA8, DNAJC27, and DNAJC28, involved with thermoregulatory protective mechanisms in mammals; and many olfactory signaling pathway related genes that are important genetic factors in the evolution of mammalian species. All these functional aspects are directly related to cattle adaptability to tropical environments.Cardiovascular diseases are associated to risk factors as obesity, hypertension and diabetes. The transforming growth factor-β1 receptors ALK1 and endoglin regulate blood pressure and vascular homeostasis. However, no studies relate the association of ALK1 and endoglin polymorphisms with cardiovascular risk factors. We analysed the predictive value of the ALK1 and endoglin polymorphisms on cardiovascular target organ damage in hypertensive and diabetic patients in 379 subjects with or without hypertension and diabetes in a Primary Care setting. The ALK1 rs2071219 polymorphism (AA genotype) is associated with a lower presence of diabetic retinopathy and with the absence of altered basal glycaemia. Being carrier of the ALK1 rs3847859 polymorphism (G allele) is associated with lower basal heart rate and with higher LDL-cholesterol levels. The endoglin rs3739817 polymorphism (AA genotype) is associated with higher levels of LDL-cholesterol, and being carrier of the endoglin rs10987759 polymorphism (C allele) is associated with higher haemoglobin levels and with an increased heart rate. Summarizing, several ALK1 and endoglin gene polymorphisms increase the risk of cardiovascular events. The analysis of these polymorphisms in populations at risk, in combination with the determination of other parameters and biomarkers, could implement the diagnosis and prognosis of susceptibility to cardiovascular damage.A kinetic model was developed using FactSage Macro Processing to simulate the re-oxidation of ultra-low carbon steel via different oxidising slags. The calculated results show good agreement with experimental laboratory thermal simulation data. Therefore, the model can be used to predict the change behaviour of slag-metal-inclusion in the re-oxidation reaction of liquid steel. It can provide prediction and guidance for an accurate secondary oxidation control process. During the slag re-oxidation process, when the oxygen in the steel is supersaturated and the slag is low in oxidation, it can easily form stick-like and dendritic shape inclusions of Al2O3 in steel. As the (FeO) content increases in slag, the oxygen transfer from slag to steel is evident, and the inclusion size increases, showing clusters and spherical shapes. In addition, supersaturated oxygen in steel easily forms unstable Al2O3-TiOx inclusions with [Ti]. As the components of liquid steel tend to be uniform, the Al2O3-TiOx inclusions will decompose and disappear, forming stable Al2O3 and TiO2 inclusions. The number of inclusions can be reduced by increasing the basicity and the ratio of CaO to Al2O3 in the initial slag.Fluorescence-based assays should be feasible in aqueous media for effectively detecting the biological factors. However, numerous sensors have limited signal transductions and low fluorescence quantum yields due to the ingerently reduced excited state energy of fluorophores in aqueous solution, which reduces their sensitivity. This necessitates a smart sensing approach with an amplified fluorescence response for analytes in aqueous solution. Herein, a new building block which self-assembles in aqueous media, giving a micellar sturcuture with the hydrophobic π-extended conjugated system at the core and hydrophilic groups at the periphery, was devised for the first time. We demonstrated that the aggregated fluorophores in a micelle induce amplified fluorescence quenching, in which the excited electron efficiently migrates through π-extended conjugated system in a micelle, as in a polymeric system. Such feature differentiates this sensing approach from the numerous fluorescence-based tools previously developed for sensitive detection. This new system exhibited highly sensitive signal transduction for specific analytes even under actual bioanalytical conditions.Despite intensive study, plant lysine catabolism beyond the 2-oxoadipate (2OA) intermediate remains unvalidated. Recently we described a missing step in the D-lysine catabolism of Pseudomonas putida in which 2OA is converted to D-2-hydroxyglutarate (2HG) via hydroxyglutarate synthase (HglS), a DUF1338 family protein. Here we solve the structure of HglS to 1.1 Å resolution in substrate-free form and in complex with 2OA. We propose a successive decarboxylation and intramolecular hydroxylation mechanism forming 2HG in a Fe(II)- and O2-dependent manner. Specificity is mediated by a single arginine, highly conserved across most DUF1338 proteins. An Arabidopsis thaliana HglS homolog coexpresses with known lysine catabolism enzymes, and mutants show phenotypes consistent with disrupted lysine catabolism. Structural and biochemical analysis of Oryza sativa homolog FLO7 reveals identical activity to HglS despite low sequence identity. Our results suggest DUF1338-containing enzymes catalyze the same biochemical reaction, exerting the same physiological function across bacteria and eukaryotes.

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