Potential Protective Function of Aβ Monomer on Tauopathies.

While soluble forms of amyloid-β (Aβ) and Tau work together to drive healthy neurons into a disease state, how their interaction may control the prion-like propagation and neurotoxicity of Tau is not fully understood. The cross-linking via disulfide bond formation is crucial for Tau oligomers to obtain stable conformers and spread between cells. This work thus focuses on how Aβ regulates this critical process.

The virulence factor candidalysin polymerizes in solution to form membrane pores and damage epithelial cells.

causes severe invasive candidiasis. infection requires the virulence factor candidalysin (CL) which damages target cell membranes. However, the mechanism that CL uses to permeabilize membranes is unclear.

Atomic View of Aqueous Cyclosporine A: Unpacking a Decades-Old Mystery.

An atomic view of a main aqueous conformation of cyclosporine A (CycA), an important 11-amino-acid macrocyclic immunosuppressant, is reported. For decades, it has been a grand challenge to determine the conformation of free CycA in an aqueous-like solution given its poor water solubility. Using a combination of X-ray and single-crystal neutron diffraction, we unambiguously resolve a unique conformer (A1) with a novel -amide between residues 11 and 1 and two water ligands that stabilize hydrogen bond networks.

Atomic view of an amyloid dodecamer exhibiting selective cellular toxic vulnerability in acute brain slices.

Atomic structures of amyloid oligomers that capture the neurodegenerative disease pathology are essential to understand disease-state causes and finding cures. Here we investigate the G6W mutation of the cytotoxic, hexameric amyloid model KV11. The mutation results into an asymmetric dodecamer composed of a pair of 30° twisted antiparallel β-sheets.

Genome Sequences of Akoni, Ashton, and Truong, Bacteriophages Isolated from Microbacterium foliorum.

Cluster EK2 Akoni, Ashton, and Truong are lytic actinobacteriophages that were isolated from soil in Florida using Microbacterium foliorum NRRL B-24224 as the host. The genomes are 54,307 bp, 54,560 bp, and 54,309 bp, respectively, and are 60% GC rich. Each genome contains a novel 13,464-bp gene that encompasses 25% of the genome.

α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine.

Despite being relatively benign and not an indicative signature of toxicity, fibril formation and fibrillar structures continue to be key factors in assessing the structure-function relationship in protein aggregation diseases. The inability to capture molecular cross-talk among key players at the tissue level before fibril formation greatly accounts for the missing link toward the development of an efficacious therapeutic intervention for Type II diabetes mellitus (T2DM). We show that human α-calcitonin gene-related peptide (α-CGRP) remodeled amylin fibrillization.

Structural Flexibility of Cyclosporine A Is Mediated by Amide - Isomerization and the Chameleonic Roles of Calcium.

Falling outside of Lipinski's rule of five, macrocyclic drugs have accessed unique binding sites of their target receptors unreachable by traditional small molecules. Cyclosporin(e) A (CycA), an extensively studied macrocyclic natural product, is an immunosuppressant with undesirable side effects such as electrolytic imbalances. In this work, a comprehensive view on the conformational landscape of CycA, its interactions with Ca, and host-guest interactions with cyclophilin A (CypA) is reported through exhaustive analyses that combine ion-mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic resonance (NMR) spectroscopy, distance-geometry modeling, and NMR-driven molecular dynamics.

Cytotoxicity of α-Helical, PSMα3 Investigated by Post-Ion-Mobility Dissociation Mass Spectrometry.

Our knowledge of amyloid formation and cytotoxicity originating from self-assembly of α-helical peptides is incomplete. PSMα3 is the only system where high-resolution X-ray crystallography and toxicity data are available. Oligomers of multiple α-helical monomers are less stable than those of β-strands, partially due to the lack of a consistent hydrogen-bonding network.

Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome.

Objectives: Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients.

Methods: In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.

Analytical and clinical validation of an LC-MS/MS method for urine leukotriene E4: A marker of systemic mastocytosis.

Objectives: Systemic mastocytosis (SM) is a disorder characterized by the excessive accumulation of clonally derived mast cells in various tissues. When triggered, mast cells release large amounts of histamine, prostaglandins and leukotrienes. Leukotriene E4 (LTE4) is the primary stable metabolite of total cysteinyl leukotrienes.

Soluble ST2 and galectin-3 in pediatric patients without heart failure.

Objectives: Soluble ST2 (ST2) and galectin-3 (Gal3) are biomarkers of myocardial fibrosis and remodeling. This study provides a foundation for the use of ST2 and Gal3 in pediatric patients by assessing values of these biomarkers among children without heart failure.

Design And Methods: Sera from 240 children, 40 males and 40 females from each of three age groups, (2-6 years, 7-11 years, and 12-17 years) without heart failure were identified from residual clinical testing.

The mental health and psychosocial effects of organized violence: a qualitative study in northern Haiti.

Historically, organized violence has been a chronic pervasive problem in Haiti. We set out to elicit Haitians' views on its effects to guide the development of interventions. In March 2006 we studied a population in the slum area of Cap-Haitien, Haiti's second largest city, and the nearby towns of Milot and Limbe.