A Structural Bioinformatics-Guided Study of Adenosine Triphosphate-Binding Cassette (ABC) Transporters and Their Substrates.

Adenosine triphosphate-binding cassette (ABC) transporters form a ubiquitous superfamily of integral membrane proteins involved in the translocation of substrates across membranes. Human ABC transporters are closely linked to the pathogenesis of diseases such as cancer, metabolic diseases, and Alzheimer's disease. In this study, four ABC transporters were chosen based on (I) their importance in humans and (II) their score in a structural bioinformatics screen aimed at the prediction of crystallisation propensity.

The role of ATP-binding Cassette subfamily B member 6 in the inner ear.

ABCB6 has been implicated in dyschromatosis universalis hereditaria, a condition characterized by hyperpigmented and hypopigmented skin macules. Dyschromatosis universalis hereditaria can also present with hearing loss. Dyschromatosis universalis hereditaria-associated mutations in ABCB6 have been reported, but the role of this protein in the inner ear has not been studied.

Rain Gardens and Rain Gauges: Students Get Hands on With Data While Evaluating Green Infrastructure at Their School.

Two modules were designed for high school science students to investigate the performance of a rain garden installed on school property. The rain garden, a green infrastructure system which allows soil infiltration, was installed to reduce impacts to urban streams and can increase the community's resilience to flooding. By involving students in the analysis of this mitigation strategy, students learned new technical skills, gained varied experiences in collecting and analyzing data, were exposed to new STEM careers, and learned about local issues that impact their community while collaborating with local professionals.

Combined transcatheter vegetectomy and leadless pacemaker implantation for endocarditis and complete heart block.

We describe a case of culture-negative right-sided endocarditis for which simultaneous transcatheter vegetectomy was performed with leadless pacemaker implantation and removal of a temporary externalized pacing system. The patient did not have a recurrence of endocarditis highlighting the safety and efficacy of same-procedure vegetation removal and pacemaker implantation. This report documents a novel approach for the treatment of cardiac implantable electronic device-associated endocarditis in poor surgical candidates who are pacemaker-dependent.

Investigation of F508del CFTR unfolding and a search for stabilizing small molecules.

Mutation of phenylalanine at position 508 in the cystic fibrosis transmembrane conductance regulator (F508del CFTR) yields a protein unstable at physiological temperatures that is rapidly degraded in the cell. This mutation is present in about 90% of cystic fibrosis patients, hence there is great interest in compounds reversing its instability. We have previously reported the expression of the mutated protein at low temperature and its purification in detergent.

Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance.

ABCG2 is an important ATP-binding cassette transporter impacting the absorption and distribution of over 200 chemical toxins and drugs. ABCG2 also reduces the cellular accumulation of diverse chemotherapeutic agents. Acquired somatic mutations in the phylogenetically conserved amino acids of ABCG2 might provide unique insights into its molecular mechanisms of transport.

Characterizing Trends in Chronic Superficial Venous Disease Treatment among Medicare Beneficiaries from 2010 to 2018.

This study describes trends in surgical versus endovascular interventions for treatment of chronic superficial venous disease (SVD) in the Medicare population. Medicare Part B data from 2010 to 2018 were obtained. Claims for SVD treatment were identified using Healthcare Common Procedure Coding System codes.

The net electrostatic potential and hydration of ABCG2 affect substrate transport.

ABCG2 is a medically important ATP-binding cassette transporter with crucial roles in the absorption and distribution of chemically-diverse toxins and drugs, reducing the cellular accumulation of chemotherapeutic drugs to facilitate multidrug resistance in cancer. ABCG2's capacity to transport both hydrophilic and hydrophobic compounds is not well understood. Here we assess the molecular basis for substrate discrimination by the binding pocket.

Updated trends in percutaneous renal arteriography among radiologists and other specialties.

Purpose: Prior studies have demonstrated an overall decline in percutaneous renal artery angioplasty with and without stenting from 1988 to 2009. We evaluated the recent utilization trends in percutaneous renal arteriography (PTRA) among radiologists and non-radiologist providers from 2010 to 2018.

Methods: Data from the 2010-2018 nationwide Medicare Part B fee-for-service database were used to tabulate case volumes for PTRA.

Pelvic Venous Disorders (PeVD).

Pelvic venous disorders (PeVDs) have replaced the concept of pelvic congestion syndrome encompassing venous origin chronic pelvic pain (VO-CPP) in women. The evaluation of women with VO-CPP includes the assessment for other causes of pelvic pain as well as imaging evaluation for pelvic varicosities measuring greater than 5 mm diameter, ovarian vein diameter, and flow direction, as well as iliac vein diameter and signs of compression. Proper identification of these patients can lead to high degrees of success eliminating chronic pelvic pain following ovarian vein embolization and/or iliac vein stenting.

Virtual Drug Repositioning as a Tool to Identify Natural Small Molecules That Synergize with Lumacaftor in F508del-CFTR Binding and Rescuing.

Cystic fibrosis is a hereditary disease mainly caused by the deletion of the Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. Cystic fibrosis remains a potentially fatal disease, but it has become treatable as a chronic condition due to some CFTR-rescuing drugs that, when used in combination, increase in their therapeutic effect due to a synergic action. Also, dietary supplementation of natural compounds in combination with approved drugs could represent a promising strategy to further alleviate cystic fibrosis symptoms.

ATP-Binding Cassette Transporters: Snap-on Complexes?

ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins in prokaryotic organisms. Much is now understood about the structure of these transporters and many reviews have been written on that subject. In contrast, less has been written on the assembly of ABC transporter complexes and this will be a major focus of this book chapter.

Supporting contaminated sites management with Multiple Criteria Decision Analysis: Demonstration of a regulation-consistent approach.

This study proposes a set of key decision-making features of the contaminated site remediation process to assist in selecting the most appropriate decision support method(s). Using a case study consistent with the requirements of the U.S.

Structure of ABCB1/P-Glycoprotein in the Presence of the CFTR Potentiator Ivacaftor.

ABCB1/P-glycoprotein is an ATP binding cassette transporter that is involved in the clearance of xenobiotics, and it affects the disposition of many drugs in the body. Conformational flexibility of the protein within the membrane is an intrinsic part of its mechanism of action, but this has made structural studies challenging. Here, we have studied different conformations of P-glycoprotein simultaneously in the presence of ivacaftor, a known competitive inhibitor.

Enrichment and Liquid Chromatography-Mass Spectrometry Analysis of Trastuzumab and Pertuzumab Using Affimer Reagents.

Trastuzumab and pertuzumab are monoclonal antibodies used in the treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer. Therapeutic proteins may undergo chemical modifications that may affect the results of bioanalytical assays, as well as their therapeutic efficacy. Modifications may arise during production and storage, as well as after administration to patients.

Radiologists and Clinical Trials: Part 2: Practical Statistical Methods for Understanding and Monitoring Independent Reader Performance.

Though many clinical trials rely on medical image evaluations for primary or key secondary endpoints, the methods to monitor reader performance are all too often mired in the legacy use of adjudication rates. If misused, this simple metric can be misleading and sometimes entirely contradictory. Furthermore, attempts to overcome the limitations of adjudication rates using de novo or ad hoc methods often ignore well-established research conducted over the last half-century and can lead to inaccurate conclusions or variable interpretations.

Radiologists and Clinical Trials: Part 1 The Truth About Reader Disagreements.

The debate over human visual perception and how medical images should be interpreted have persisted since X-rays were the only imaging technique available. Concerns over rates of disagreement between expert image readers are associated with much of the clinical research and at times driven by the belief that any image endpoint variability is problematic. The deeper understanding of the reasons, value, and risk of disagreement are somewhat siloed, leading, at times, to costly and risky approaches, especially in clinical trials.

Imaging approach to COVID-19 associated pulmonary embolism.

The novel coronavirus disease-2019 (COVID-19) illness and deaths, caused by the severe acute respiratory syndrome coronavirus-2, continue to increase. Multiple reports highlight the thromboembolic complications, such as pulmonary embolism (PE), in COVID-19. Imaging plays an essential role in the diagnosis and management of COVID-19 patients with PE.

ATP binding cassette importers in eukaryotic organisms.

ATP-binding cassette (ABC) transporters are ubiquitous across all realms of life. Dogma suggests that bacterial ABC transporters include both importers and exporters, whilst eukaryotic members of this family are solely exporters, implying that ABC import function was lost during evolution. This view is being challenged, for example energy-coupling factor (ECF)-type ABC importers appear to fulfil important roles in both algae and plants where they form the ABCI sub-family.

Five Steps to Leading Your Team in the Virtual COVID-19 Workplace.

The emergence of COVID-19 has presented employees and employers new challenges as many employees and managers were forced to work in a remote environment for the first time. For many reasons, managing virtual teams is different than managing employees in a traditional face-to-face office environment. Although many managers have been learning how to lead their virtual teams over the last several months, we offer five steps for leaders to follow for how to maximize the effectiveness of a remote workplace.

Geophysical Assessment of a Proposed Landfill Site in Fredericktown, Missouri.

In cooperation with the U.S. Environmental Protection Agency (EPA), the U.

What monomeric nucleotide binding domains can teach us about dimeric ABC proteins.

The classic conceptualization of ATP binding cassette (ABC) transporter function is an ATP-dependent conformational change coupled to transport of a substrate across a biological membrane via the transmembrane domains (TMDs). The binding of two ATP molecules within the transporter's two nucleotide binding domains (NBDs) induces their dimerization. Despite retaining the ability to bind nucleotides, isolated NBDs frequently fail to dimerize.