Small Molecule Assembly Agonist Alters the Dynamics of Hepatitis B Virus Core Protein Dimer and Capsid.

Chronic hepatitis B virus (HBV) poses a significant public health burden worldwide, encouraging the search for curative antivirals. One approach is capsid assembly modulators (CAMs), which are assembly agonists. CAMs lead to empty and defective capsids, inhibiting the formation of new viruses, and can also lead to defects in the release of the viral genome, inhibiting new infections.

Targeted metabolomics analysis approach to unravel the biofilm formation pathways of Enterococcus faecalis clinical isolates.

Aim: (i) To characterize Enterococcus faecalis biofilm formation pathways by semi-targeted metabolomics and targeted nitrogen panel analysis of strong (Ef63) and weak (Ef 64) biofilm forming E. faecalis clinical isolates and (ii) to validate the identified metabolic markers using targeted inhibitors.

Methodology: Previous proteomics profiling of E.

Urine tricarboxylic acid cycle metabolites and risk of end stage kidney disease in patients with type 2 diabetes.

Context: Metabolites in tricarboxylic acid (TCA) pathway have pleiotropic functions.

Objective: To study the association between urine TCA cycle metabolites and the risk for chronic kidney disease (CKD) progression in individuals with type 2 diabetes.

Design, Setting And Participants: A prospective study in a discovery (n = 1826) and a validation (n = 1235) cohort of type 2 diabetes in a regional hospital and a primary care facility.

Lipidomics Workflow for Analyzing Lipid Profiles Using Multiple Reaction Monitoring (MRM) in Liver Homogenate of Mice with Non-alcoholic Steatohepatitis (NASH).

Non-alcoholic steatohepatitis (NASH) is a condition characterized by inflammation and hepatic injury/fibrosis caused by the accumulation of ectopic fats in the liver. Recent advances in lipidomics have allowed the identification and characterization of lipid species and have revealed signature patterns of various diseases. Here, we describe a lipidomics workflow to assess the lipid profiles of liver homogenates taken from a NASH mouse model.

Sensitive ex vivo human skin transdermal assay testing method with mass spectrometric analysis for cosmetics application.

Background: Cosmetics manufacturers are focused on cosmetic delivery systems into the skin, but the level of diffusion of the systems in the skin tissues is not well understood. The current methods, such as Franz diffusion, assess analyte diffusion in the whole skin or artificial membranes, which has limitations for understanding skin delivery systems.

Aims: Our study aimed to create a transdermal delivery method which is based on dermal-epidermal separation of human skin, allowing us to assess each layer of skin separately for its efficacy.

Amino acid profile of skeletal muscle loss in type 2 diabetes: Results from a 7-year longitudinal study in asians.

Aims: Little is known about pathophysiology of sarcopenia in diabetes. We aimed to study amino acid profile associated with skeletal muscle mass loss longitudinally in Type 2 Diabetes Mellitus (T2DM).

Methods: This is a prospective study of 1140 patients aged 56.

Exacerbation of cardiovascular ageing by diabetes mellitus and its associations with acyl-carnitines.

Objective: To demonstrate differences in cardiovascular structure and function between diabetic and non-diabetic older adults. To investigate associations between acyl-carnitines and cardiovascular function as indexed by imaging measurements.

Methods: A community-based cohort of older adults without cardiovascular disease underwent current cardiovascular imaging and metabolomics acyl-carnitines profiling based on current and archived sera obtained fifteen years prior to examination.

Amino acid differences between diabetic older adults and non-diabetic older adults and their associations with cardiovascular function.

Background: Ageing and insulin resistant states such as diabetes mellitus frequently coexist and increase the risk of cardiovascular disease development among older adults. Here we investigate metabolic differences in amino acid profiles between ageing and diabetes mellitus, and their associations with cardiovascular function.

Methods: In a group of community older adults we performed echocardiography, cardiac magnetic resonance imaging as well as cross sectional and longitudinal metabolomics profiling based on current and archived sera obtained fifteen years prior to examination.

Multi-omics tools for studying microbial biofilms: current perspectives and future directions.

The advent of omics technologies has greatly improved our understanding of microbial biology, particularly in the last two decades. The field of microbial biofilms is, however, relatively new, consolidated in the 1980s. The morphogenic switching by microbes from planktonic to biofilm phenotype confers numerous survival advantages such as resistance to desiccation, antibiotics, biocides, ultraviolet radiation, and host immune responses, thereby complicating treatment strategies for pathogenic microorganisms.

Evolution of Intermediates during Capsid Assembly of Hepatitis B Virus with Phenylpropenamide-Based Antivirals.

Self-assembly of virus capsids is a potential target for antivirals due to its importance in the virus lifecycle. Here, we investigate the effect of phenylpropenamide derivatives B-21 and AT-130 on the assembly of hepatitis B virus (HBV) core protein. Phenylpropenamides are widely believed to yield assembly of spherical particles resembling native, empty HBV capsids.

Molecular jenga: the percolation phase transition (collapse) in virus capsids.

Virus capsids are polymeric protein shells that protect the viral cargo. About half of known virus families have icosahedral capsids that self-assemble from tens to thousands of subunits. Capsid disassembly is critical to the lifecycles of many viruses yet is poorly understood.

Characterization of Virus Capsids and Their Assembly Intermediates by Multicycle Resistive-Pulse Sensing with Four Pores in Series.

Virus self-assembly is a critical step in the virus lifecycle. Understanding how viruses assemble and disassemble provides needed insight into developing antiviral pharmaceuticals. Few tools offer sufficient resolution to study assembly intermediates that differ in size by a few dimers.

A molecular breadboard: Removal and replacement of subunits in a hepatitis B virus capsid.

Hepatitis B virus (HBV) core protein is a model system for studying assembly and disassembly of icosahedral structures. Controlling disassembly will allow re-engineering the 120 subunit HBV capsid, making it a molecular breadboard. We examined removal of subunits from partially crosslinked capsids to form stable incomplete particles.

Nanofluidic Devices with 8 Pores in Series for Real-Time, Resistive-Pulse Analysis of Hepatitis B Virus Capsid Assembly.

To improve the precision of resistive-pulse measurements, we have used a focused ion beam instrument to mill nanofluidic devices with 2, 4, and 8 pores in series and compared their performance. The in-plane design facilitates the fabrication of multiple pores in series which, in turn, permits averaging of the series of pulses generated from each translocation event. The standard deviations (σ) of the pulse amplitude distributions decrease by 2.

Detection of late intermediates in virus capsid assembly by charge detection mass spectrometry.

The assembly of hundreds of identical proteins into an icosahedral virus capsid is a remarkable feat of molecular engineering. How this occurs is poorly understood. Key intermediates have been anticipated at the end of the assembly reaction, but it has not been possible to detect them.