Screening for Fabry disease in patients on Hemodialysis.

Background: Fabry disease is an under-recognized X-linked lysosomal storage disorder characterized by the accumulation of trihexosylceramides in multifarious tissues, leading to end-organ damage, including progressive renal failure. Antecedent screening studies worldwide have shown inconsistent prevalence in the hemodialysis population. We conducted this study to screen for Fabry disease in patients undergoing dialysis at a tertiary care hospital.

The PARP inhibitor rucaparib blocks SARS-CoV-2 virus binding to cells and the immune reaction in models of COVID-19.

Background And Purpose: To date, there are limited options for severe Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus. As ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host; we have, here, assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19.

Experimental Approach: The effects of PARP inhibitors on virus uptake were assessed in cell-based experiments using multiple variants of SARS-CoV-2.

Mapping of the Lipid-Binding Regions of the Antifungal Protein NFAP2 by Exploiting Model Membranes.

Fungal infections with high mortality rates represent an increasing health risk. The antifungal protein 2 (NFAP2) is a small, cysteine-rich, cationic protein exhibiting potent anti- activity. As the underlying mechanism, pore formation has been demonstrated; however, molecular level details on its membrane disruption action are lacking.

Synthesis and estrogenic activity of BODIPY-labeled estradiol conjugates.

Novel BODIPY-estradiol conjugates have been synthesized by selecting position C-3-O for labeling. The conjugation strategy was based on Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or etherification. Estradiol derivatives used as azide partners bearing an ω-azidoalkyl function through C-C-long linkers have been prepared.

Dynamic Structures of Bioactive Proteins as Determined by Nuclear Magnetic Resonance.

According to "Panta rhei", a phrase by the ancient Greeks, you cannot enter the same river two times [...

Hard nut to crack: Solving the disulfide linkage pattern of the Neosartorya (Aspergillus) fischeri antifungal protein 2.

As a consequence of the fast resistance spreading, a limited number of drugs are available to treat fungal infections. Therefore, there is an urgent need to develop new antifungal treatment strategies. The features of a disulfide bond-stabilized antifungal protein, NFAP2 secreted by the mold Neosartorya (Aspergillus) fischeri render it to be a promising template for future protein-based antifungal drug design, which requires knowledge about the native disulfide linkage pattern as it is one of the prerequisites for biological activity.

Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Antifungal Protein, AFP.

Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation.

DMSO-Induced Unfolding of the Antifungal Disulfide Protein PAF and Its Inactive Variant: A Combined NMR and DSC Study.

PAF and related antifungal proteins are promising antimicrobial agents. They have highly stable folds around room temperature due to the presence of 3-4 disulfide bonds. However, unfolded states persist and contribute to the thermal equilibrium in aqueous solution, and low-populated states might influence their biological impact.

Mapping the functional expression of auxiliary subunits of K1.1 in glioblastoma.

Glioblastoma (GBM) is the most aggressive glial tumor, where ion channels, including K1.1, are candidates for new therapeutic options. Since the auxiliary subunits linked to K1.

Functional analysis of the bZIP-type transcription factors AtfA and AtfB in .

Transcription factors (TFs) with the basic leucin zipper domain are key elements of the stress response pathways in filamentous fungi. In this study, we functionally characterized the two bZIP type TFs AtfA and AtfB by deletion () and overexpression (OE) of their encoding genes in all combination: OE, OE, OE, OE and OEOE in . Based on our previous studies, increased the sensitivity of the fungus to oxidative stress mediated by menadione sodium bisulfite (MSB) and tert-butylhydroperoxide (BOOH), while was not sensitive to any oxidative stress generating agents, namely MSB, BOOH and diamide at all.

Semisynthetic teicoplanin derivatives with dual antimicrobial activity against SARS-CoV-2 and multiresistant bacteria.

Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2.

The Importance of Mg -Free State in Nucleotide Exchange of Oncogenic K-Ras Mutants.

For efficient targeting of oncogenic K-Ras interaction sites, a mechanistic picture of the Ras-cycle is necessary. Herein, we used NMR relaxation techniques and molecular dynamics simulations to decipher the role of slow dynamics in wild-type and three oncogenic P-loop mutants of K-Ras. Our measurements reveal a dominant two-state conformational exchange on the ms timescale in both GDP- and GTP-bound K-Ras.

Resonance assignment of the Shank1 PDZ domain.

Shank proteins are among the most abundant and well-studied postsynaptic scaffold proteins. Their PDZ domain has unique characteristics as one of its loop regions flanking the ligand-binding site is uniquely long and has also been implicated in the formation of PDZ dimers. Here we report the initial characterization of the Shank1 PDZ domain by solution NMR spectroscopy.

Plasma cell rich acute rejection: Risk factors, treatment and outcomes.

Plasma cell-rich rejection is a rare and poorly defined entity. Its treatment is not clearly defined and has universally poor prognosis. More data should be published from various transplant centers around the world to identify the treatment that has the best outcomes and to formulate treatment guidelines for these cases.

Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity.

P-glycoprotein (Pgp, ABCB1) is a member of one of the largest families of active transporter proteins called ABC transporters. Thanks to its expression in tissues with barrier functions and its broad substrate spectrum, it is an important determinant of the absorption, metabolism and excretion of many drugs. Pgp and/or some other drug transporting ABC proteins (e.

Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication.

The protracted global COVID-19 pandemic urges the development of new drugs against the causative agent SARS-CoV-2. The clinically used glycopeptide antibiotic, teicoplanin, emerged as a potential antiviral, and its efficacy was improved with lipophilic modifications. This prompted us to prepare new lipophilic apocarotenoid conjugates of teicoplanin, its pseudoaglycone and the related ristocetin aglycone.

Molecular and comparative genomic analyses reveal evolutionarily conserved and unique features of the Schizosaccharomyces japonicus mycelial growth and the underlying genomic changes.

Fungal pathogens, from phytopathogenic fungus to human pathogens, are able to alternate between the yeast-like form and filamentous forms. This morphological transition (dimorphism) is in close connection with their pathogenic lifestyles and with their responses to changing environmental conditions. The mechanisms governing these morphogenetic conversions are still not fully understood.

Aminoalkylamides of Eremomycin Exhibit an Improved Antibacterial Activity.

After decades, the glycopeptide vancomycin is still the preferred antibiotic against resistant strains of Gram-positive bacteria. Although its clinical use is strictly regulated, the gradual spread of vancomycin-resistant bacteria, such as glycopeptide-resistant and glycopeptide-intermediate and vancomycin-resistant spp., is a serious health problem.

An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin.

Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emission ratiometric flow cytometry method based on F66, a 3-hydroxiflavon derivative, and demonstrate that 6-ketocholestanol, cholesterol and 7-dehydrocholesterol, saturated stearic acid (SA) and ω-6 γ-linolenic acid (GLA) increase, while ω-3 α-linolenic acid (ALA) decreases the DP. These changes do not correlate with alterations in cell viability or membrane fluidity.

Statin-boosted cellular uptake and endosomal escape of penetratin due to reduced membrane dipole potential.

Background And Purpose: Cell penetrating peptides are promising tools for delivery of cargo into cells, but factors limiting or facilitating their cellular uptake are largely unknown. We set out to study the effect of the biophysical properties of the cell membrane on the uptake of penetratin, a cell penetrating peptide.

Experimental Approach: Using labelling with pH-insensitive and pH-sensitive dyes, the kinetics of cellular uptake and endo-lysosomal escape of penetratin were studied by flow cytometry.

Catastrophic Antiphospholipid Syndrome in Immune Thrombocytopenic Purpura - Beyond Tenuous Concomitance!

Significance of antiphospholipid antibodies in immune thrombocytopenic purpura is debatable and pose a diagnostic and therapeutic dilemma. Catastrophic antiphospholipid syndrome is a rare life-threatening entity, occurring in patients with antiphospholipid syndrome, usually after a triggering event. We describe an adult lady of chronic immune thrombocytopenic purpura (in remission) with antiphospholipid antibodies, who presented with rapidly progressive renal failure and had primary antiphospholipid syndrome nephropathy.

Solution Structure, Dynamics, and New Antifungal Aspects of the Cysteine-Rich Miniprotein PAFC.

The genome of Q176 contains a gene coding for the 88-amino-acid (aa)-long glycine- and cysteine-rich antifungal protein C (PAFC). After maturation, the secreted antifungal miniprotein (MP) comprises 64 aa and shares 80% aa identity with the bubble protein (BP) from , which has a published X-ray structure. Our team expressed isotope (N, C)-labeled, recombinant PAFC in high yields, which allowed us to determine the solution structure and molecular dynamics by nuclear magnetic resonance (NMR) experiments.