Target-Templated Construction of Functional Proteomimetics Using Photo-Foldamer Libraries.

Current methods for proteomimetic engineering rely on structure-based design. Here we describe a design strategy that allows the construction of proteomimetics against challenging targets without a priori characterization of the target surface. Our approach employs (i) a 100-membered photoreactive foldamer library, the members of which act as local surface mimetics, and (ii) the subsequent affinity maturation of the primary hits using systems chemistry.

May Measurement Month 2021: an analysis of blood pressure screening results from Hungary.

Elevated blood pressure (BP) is the most important risk factor for cardiovascular diseases (CVDs), which are still the leading cause of mortality in Hungary. Therefore, screening programmes identifying subjects with hypertension have an important role in CVD prevention. In 2017, the International Society of Hypertension initiated May Measurement Month (MMM) aimed at raising awareness of elevated BP.

Early and selective localization of tau filaments to glutamatergic subcellular domains within the human anterodorsal thalamus.

Widespread cortical accumulation of misfolded pathological tau proteins (ptau) in the form of paired helical filaments is a major hallmark of Alzheimer's disease. Subcellular localization of ptau at various stages of disease progression is likely to be informative of the cellular mechanisms involving its spread. Here, we found that the density of ptau within several distinct rostral thalamic nuclei in post-mortem human tissue (n = 25 cases) increased with the disease stage, with the anterodorsal nucleus (ADn) consistently being the most affected.

Presynaptic nanoscale components of retrograde synaptic signaling.

While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell-dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes.

Computational Studies on the Diastereospecific Lithium Variant of Oppenauer Oxidation of a Tofisopam Intermediate.

During the synthesis of tofisopam drug substance, an interesting diastereospecific lithium variant of Oppenauer oxidation was observed and investigated by density functional theory (DFT) calculations. The computations revealed energetic differences caused by steric differences between the diastereomers that might provide an explanation for the experimentally formed products. In addition, the trend in the measured NMR shifts was also in line with the computed values, which allowed the assignment of the absolute configuration of the diastereomers.

The Physiological Basis of Alfalfa Plant Height Establishment.

Plant height plays an important role in crop yield, product quality, and cultivation management. However, the physiological mechanisms that regulate the establishment of plant height in alfalfa plants remain unclear. Herein, we measured plant height traits, leaf characteristics, photosynthetic physiology, cell wall composition, and endogenous hormone contents of tall- and short-stalked alfalfa materials at different reproductive periods.

Coloration differences in three Camellia reticulata Lindl. cultivars: 'Tongzimian', 'Shizitou' and 'Damanao'.

Camellia reticulata Lindl., also known as Yunnan Camellia, is an important ornamental plant in China, especially for its large and stunning flowers. A comprehensive understanding of their coloration mechanisms can aid breeders in developing new cultivars and improving their ornamental value; however, it is still unclear in Yunnan Camellia, especially in mixed-color flowers.

Epoxy Resin-Based Materials Containing Natural Additives of Plant Origin Dedicated to Rail Transport.

The presented study is focused on the modification of commercially available epoxy resin with flame retardants by means of using natural substances, including quercetin hydrate and potato starch. The main aim was to obtain environmentally friendly material dedicated to rail transport that is resistant to the aging process during exploitation but also more prone to biodegradation in environmental conditions after usage. Starch is a natural biopolymer that can be applied as a pro-ecological filler, which may contribute to degradation in environmental conditions, while quercetin hydrate is able to prevent a composite from premature degradation during exploitation.

Biocide Tolerance and Impact of Sanitizer Concentrations on the Antibiotic Resistance of Bacteria Originating from Cheese.

In this study, we determined and identified the bacterial diversity of different types of artisanal and industrially produced cheese. The antibiotic (erythromycin, chloramphenicol, kanamycin, ampicillin, clindamycin, streptomycin, tetracycline, and gentamicin) and biocide (peracetic acid, sodium hypochlorite, and benzalkonium chloride) resistance of clinically relevant bacteria was determined as follows: , , sp., , , , , , , , sp.

Correction: Peptide epitope-imprinted polymer microarrays for selective protein recognition. Application for SARS-CoV-2 RBD protein.

[This corrects the article DOI: 10.1039/D1SC04502D.].

Does the Sign of Charge Affect the Surface Affinity of Simple Ions?

The role the charge sign of simple ions plays in determining their surface affinity in aqueous solutions is investigated by computer simulation methods. For this purpose, the free surface of aqueous solutions of fictitious salts is simulated at finite concentration both with nonpolarizable point-charge and polarizable Gaussian-charge potential models. The salts consist of monovalent cations and anions that are, apart from the sign of their charge, identical to each other.

Surface Affinity of Tetramethylammonium Iodide in Aqueous Solutions: A Combined Experimental and Computer Simulation Study.

The surface affinity of tetramethylammonium iodide (TMAI) in aqueous solutions is investigated by surface tension measurements and molecular dynamics computer simulations. Experiments, performed in the entire composition range of solubility using the pendant drop method with two different setups, clearly reveal that TMAI is a weakly capillary active salt. Computer simulations performed with the AMBER force field reproduce the experimental data very well, while two other major force fields (i.

MELAS: Phenotype Classification into Classic-versus-Atypical Presentations.

Background And Purpose: An increased number of pathogenic variants have been described in mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS). Different imaging presentations have emerged in parallel with a growing recognition of clinical and outcome variability, which pose a diagnostic challenge to neurologists and radiologists and may impact an individual patient's response to therapeutic interventions. By evaluating clinical, neuroimaging, laboratory, and genetic findings, we sought to improve our understanding of the sources of potential phenotype variability in patients with MELAS.

Interhemispheric differences of pyramidal cells in the primary motor cortices of schizophrenia patients investigated postmortem.

Motor disturbances are observed in schizophrenia patients, but the neuroanatomical background is unknown. Our aim was to investigate the pyramidal cells of the primary motor cortex (BA 4) in both hemispheres of postmortem control and schizophrenia subjects-8 subjects in each group-with 2.5-5.

Impact of COVID-19 Related Restrictions on Infections in Children with Cancer or after Hematopoietic SCT.

Background: Infections are a major concern for immunocompromised children. We investigated whether non-pharmaceutical interventions (NPIs) implemented in the general population during the coronavirus disease 2019 (COVID-19) pandemic in Germany had an impact on frequency, type and severity of infections in these patients.

Patients And Methods: We analyzed all admissions to the clinic of pediatric hematology, oncology and stem cell transplantation (SCT) with (suspected) infection or fever of unknown origin (FUO) from 2018 to 2021.

Resistive Switching Memory Cell Property Improvement by Al/SrZrTiO/Al/SrZrTiO/ITO with Embedded Al Layer.

The SrZrTiO (SZT) thin film prepared by sol-gel process for the insulator of resistive random-access memory (RRAM) is presented. Al was embedded in the SZT thin film to enhance the switching characteristics. Compared with the pure SZT thin-film RRAM, the RRAM with the embedded Al in SZT thin film demonstrated outstanding device parameter improvements, such as a resistance ratio higher than 10, lower operation voltage (V = -0.

Additive damage in the thromboxane related vasoconstriction and bradykinin relaxation of intramural coronary resistance arterioles in a rodent model of andropausal hypertension.

Hypertension and andropause both accelerate age-related vascular deterioration. We aimed to evaluate the effects of angiotensin-II induced hypertension and deficiency of testosterone combined regarding the resistance coronaries found intramurally. Four male groups were formed from the animals: control group (Co, n = 10); the group that underwenr orchidectomy (ORC, n = 13), those that received an infusion of angiotensin-II (AII, n = 10) and a grous that received AII infusion and were also surgically orchidectomized (AII + ORC, n = 8).

Maternal care of the whole litter improves the success rate of diabetes in pregnancy in rats.

Induction of diabetes mellitus by streptozotocin (STZ) in rats at birth is of high mortality and low success rate when male puppies are separated from females, prioritizing females breastfeeding. Cross-parental care of the entire litter and SZT-induced diabetes up to 12 h post-birth become with high success rate, low animal death, and females with glycaemia >140 mg/dL on the 90 postnatal day. Cross-parental care is more effective in STZ-induction of diabetes, which is maintained during pregnancy (diabetes in pregnancy), than the conventional protocol of male separation at birth.

Optimized Sample Preparation and Microscale Separation Methods for High-Sensitivity Analysis of Hydrophilic Peptides.

The optimization of solid-phase extraction (SPE) purification and chromatographic separation is usually neglected during proteomics studies. However, the effects on detection performance are not negligible, especially when working with highly glycosylated samples. We performed a comparative study of different SPE setups, including an in-house optimized method and reversed-phase chromatographic gradients for the analysis of highly glycosylated plasma fractions as a model sample for glycopeptide analysis.

Glycosaminoglycan Analysis of FFPE Tissues from Prostate Cancer and Benign Prostate Hyperplasia Patients Reveals Altered Regulatory Functions and Independent Markers for Survival.

Prostate cancer is one of the most frequent cancer types among men. Several biomarkers and risk assessment methods are already available; however, enhancing their selectivity and sensitivity is still necessary. For improving therapeutic decisions, both basic and clinical research studies are still ongoing for a better understanding of the underlying molecular mechanisms.

Covalent inhibitors of bacterial peptidoglycan biosynthesis enzyme MurA with chloroacetamide warhead.

MurA (UDP-N-acetylglucosamine enolpyruvyl transferase) catalyzes the first committed step in the cytoplasmic part of peptidoglycan biosynthesis and is a validated target enzyme for antibacterial drug discovery; the inhibitor fosfomycin has been used clinically for decades. Like fosfomycin, most MurA inhibitors are small heterocyclic compounds that inhibit the enzyme by forming a covalent bond with the active site cysteine. The reactive chloroacetamide group was selected from a series of suitable electrophilic thiol-reactive warheads.

Proteomic Analysis of Lung Cancer Types-A Pilot Study.

Lung cancer is the leading cause of tumor-related mortality, therefore significant effort is directed towards understanding molecular alterations occurring at the origin of the disease to improve current treatment options. The aim of our pilot-scale study was to carry out a detailed proteomic analysis of formalin-fixed paraffin-embedded tissue sections from patients with small cell or non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). Tissue surface digestion was performed on relatively small cancerous and tumor-adjacent normal regions and differentially expressed proteins were identified using label-free quantitative mass spectrometry and subsequent statistical analysis.

Accelerated Aging of Epoxy Biocomposites Filled with Cellulose.

The presented research concerns the mechanochemical modification of a snap-cure type of epoxy resin, A.S. SET 1010, with the addition of different amounts of cellulose (0, 2, 5, 10, 15 and 20 per 100 resin), for a novel, controlled-degradation material with possible application in the production of passenger seats in rail transport.

Reversible Redox Chemistry of Anionic Imidazole-2-thione-Fused 1,4-Dihydro-1,4-diphosphinines.

Anionic 1,4-dihydro-1,4-diphosphinines were synthesized from tricyclic 1,4-diphosphinines and isolated as blue powdery salts M[-]. Reaction of solutions of these monoanions with iodomethane led to -methylated compounds -. An oxidation/reduction cycle was examined, starting from solutions of K[] via P-P coupled product and back to K[], and the recyclability and redox chemistry of this cycle were confirmed by experimental and simulated cyclic voltammetry analysis, which is proposed as a potential 2-electron cathode for rechargeable cells.