Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial.

Importance: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation.

Objective: To determine the effectiveness and safety of endobronchial coil treatment.

Design, Setting, And Participants: Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015.

Patients With a History of Chemotherapy and Isolated del(20q) With Minimal Myelodysplasia Have an Indolent Course.

Objectives: Isolated deletion (20q) is relatively common in myeloid neoplasms and has been rarely reported in cases of therapy-related myelodysplastic syndrome (MDS). Our aim was to characterize cases of isolated del(20q) in bone marrow biopsy specimens from patients with a history of chemotherapy with morphologic findings insufficient for a diagnosis of MDS.

Methods: In this retrospective study from one institution, we identified 22 patients with isolated del(20q) and no or minimal dysplasia and evaluated clinical and pathologic characteristics.

Tracking solvent and protein movement during CO2 release in carbonic anhydrase II crystals.

Carbonic anhydrases are mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3 (-) Previously, the X-ray crystal structures of CO2-bound holo (zinc-bound) and apo (zinc-free) human carbonic anhydrase IIs (hCA IIs) were captured at high resolution. Here, we present sequential timeframe structures of holo- [T = 0 s (CO2-bound), 50 s, 3 min, 10 min, 25 min, and 1 h] and apo-hCA IIs [T = 0 s, 50 s, 3 min, and 10 min] during the "slow" release of CO2 Two active site waters, WDW (deep water) and WDW' (this study), replace the vacated space created on CO2 release, and another water, WI (intermediate water), is seen to translocate to the proton wire position W1. In addition, on the rim of the active site pocket, a water W2' (this study), in close proximity to residue His64 and W2, gradually exits the active site, whereas His64 concurrently rotates from pointing away ("out") to pointing toward ("in") active site rotameric conformation.

Solution structure of an "open" E. coli Pol III clamp loader sliding clamp complex.

Sliding clamps are opened and loaded onto primer template junctions by clamp loaders, and once loaded on DNA, confer processivity to replicative polymerases. Previously determined crystal structures of eukaryotic and T4 clamp loader-clamp complexes have captured the sliding clamps in either closed or only partially open interface conformations. In these solution structure studies, we have captured for the first time the clamp loader-sliding clamp complex from Escherichia coli using size exclusion chromatography coupled to small angle X-ray scattering (SEC-SAXS).

Characterization of the Adeno-Associated Virus 1 and 6 Sialic Acid Binding Site.

Unlabelled: The adeno-associated viruses (AAVs), which are being developed as gene delivery vectors, display differential cell surface glycan binding and subsequent tissue tropisms. For AAV serotype 1 (AAV1), the first viral vector approved as a gene therapy treatment, and its closely related AAV6, sialic acid (SIA) serves as their primary cellular surface receptor. Toward characterizing the SIA binding site(s), the structure of the AAV1-SIA complex was determined by X-ray crystallography to 3.

Mapping Antigenic Epitopes on the Human Bocavirus Capsid.

Unlabelled: Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.

Kinetic and X-ray crystallographic investigations on carbonic anhydrase isoforms I, II, IX and XII of a thioureido analog of SLC-0111.

SLC-0111 (4-(4-fluorophenylureido)-benzenesulfonamide) is the first carbonic anhydrase (CA, EC 4.2.1.

Production of biorenewable styrene: utilization of biomass-derived sugars and insights into toxicity.

Fermentative production of styrene from glucose has been previously demonstrated in Escherichia coli. Here, we demonstrate the production of styrene from the sugars derived from lignocellulosic biomass depolymerized by fast pyrolysis. A previously engineered styrene-producing strain was further engineered for utilization of the anhydrosugar levoglucosan via expression of levoglucosan kinase.

Solution study of the Escherichia coli DNA polymerase III clamp loader reveals the location of the dynamic ψχ heterodimer.

Several X-ray crystal structures of the E. coli core clamp loader containing the five core (δ', δ, and three truncated γ) subunits have been determined, but they lack the ψ and χ subunits. We report the first solution structure of the complete seven-subunit clamp loader complex using small angle X-ray scattering.

Sulfonamide inhibition studies of the α-carbonic anhydrase from the gammaproteobacterium Thiomicrospira crunogena XCL-2, TcruCA.

We report a sulfonamide/sulfamate inhibition study of the α-carbonic anhydrase (CA, EC 4.2.1.

Carbon Dioxide "Trapped" in a β-Carbonic Anhydrase.

Carbonic anhydrases (CAs) are enzymes that catalyze the hydration/dehydration of CO2/HCO3(-) with rates approaching diffusion-controlled limits (kcat/KM ∼ 10(8) M(-1) s(-1)). This family of enzymes has evolved disparate protein folds that all perform the same reaction at near catalytic perfection. Presented here is a structural study of a β-CA (psCA3) expressed in Pseudomonas aeruginosa, in complex with CO2, using pressurized cryo-cooled crystallography.

A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX.

Human carbonic anhydrase (CA; EC 4.2.1.

Postural Control Deficits in Autism Spectrum Disorder: The Role of Sensory Integration.

We investigated the nature of sensory integration deficits in postural control of young adults with ASD. Postural control was assessed in a fixed environment, and in three environments in which sensory information about body sway from visual, proprioceptive or both channels was inaccurate. Furthermore, two levels of inaccurate information were used within each channel (gain 1 and 1.

Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function.

The most aggressive tumour cells, which often reside in hypoxic environments, rely on glycolysis for energy production. Thereby they release vast amounts of lactate and protons via monocarboxylate transporters (MCTs), which exacerbates extracellular acidification and supports the formation of a hostile environment. We have studied the mechanisms of regulated lactate transport in MCF-7 human breast cancer cells.

Structure of neurotropic adeno-associated virus AAVrh.8.

Adeno-associated virus rhesus isolate 8 (AAVrh.8) is a leading vector for the treatment of neurological diseases due to its efficient transduction of neuronal cells and reduced peripheral tissue tropism. Toward identification of the capsid determinants for these properties, the structure of AAVrh.

Observed surface lysine acetylation of human carbonic anhydrase II expressed in Escherichia coli.

Acetylation of surface lysine residues of proteins has been observed in Escherichia coli (E. coli), an organism that has been extensively utilized for recombinant protein expression. This post-translational modification is shown to be important in various processes such as metabolism, stress-response, transcription, and translation.

Structural and biophysical characterization of the α-carbonic anhydrase from the gammaproteobacterium Thiomicrospira crunogena XCL-2: insights into engineering thermostable enzymes for CO2 sequestration.

Biocatalytic CO2 sequestration to reduce greenhouse-gas emissions from industrial processes is an active area of research. Carbonic anhydrases (CAs) are attractive enzymes for this process. However, the most active CAs display limited thermal and pH stability, making them less than ideal.

Video-Assisted Thoracic Surgery After Median Sternotomy for Cardiac Surgery.

Video-assisted thoracic surgery (VATS) lobectomy has become a standard approach for early stage 1 lung cancer. However, concerns still remain regarding certain clinical situations, such as potential damage to the heart or bypass grafts when VATS is performed after median sternotomy for cardiac surgery. In this article, techniques are described to minimize risk to an internal mammary artery graft during a VATS anatomic pulmonary resection in this group of patients.

Case report of non-healing surgical wound treated with dehydrated human amniotic membrane.

Introduction: Non-healing wounds can pose a medical challenge as in the case of vasculopathic venostasis resulting in a surgical ulcer. When traditional approaches to wound care fail, an amniotic patch (a dehydrated tissue allograft derived from human amnion) can function as a biologic scaffold to facilitate and enhance tissue regeneration and rehabilitation.

Background: Amniotic AlphaPatches contain concentrated molecules of PGE2, WNT4, and GDF-11 which have angiogenic, trophic, and anti-inflammatory effects on tissues that may be useful in enhancing wound healing.

Mapping Selective Inhibition of the Cancer-Related Carbonic Anhydrase IX Using Structure-Activity Relationships of Glucosyl-Based Sulfamates.

Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX.

Developing Federal Clinical Care Recommendations for Men.

U.S. men experience substantial sexual and reproductive health needs across the life span.