Deuterium spin relaxation of fractionally deuterated ribonuclease H using paired 475 and 950 MHz NMR spectrometers.

Deuterium (H) spin relaxation of CHD methyl groups has been widely applied to investigate picosecond-to-nanosecond conformational dynamics in proteins by solution-state NMR spectroscopy. The B dependence of the H spin relaxation rates is represented by a linear relationship between the spectral density function at three discrete frequencies J(0), J(ω) and J(2ω). In this study, the linear relation between H relaxation rates at B fields separated by a factor of two and the interpolation of rates at intermediate frequencies are combined for a more robust approach for spectral density mapping.

NUScon: a community-driven platform for quantitative evaluation of nonuniform sampling in NMR.

Although the concepts of nonuniform sampling (NUS​​​​​​​) and non-Fourier spectral reconstruction in multidimensional NMR began to emerge 4 decades ago , it is only relatively recently that NUS has become more commonplace. Advantages of NUS include the ability to tailor experiments to reduce data collection time and to improve spectral quality, whether through detection of closely spaced peaks (i.e.

NMR chemical shift assignments of RNA oligonucleotides to expand the RNA chemical shift database.

RNAs play myriad functional and regulatory roles in the cell. Despite their significance, three-dimensional structure elucidation of RNA molecules lags significantly behind that of proteins. NMR-based studies are often rate-limited by the assignment of chemical shifts.

RING NMR dynamics: software for analysis of multiple NMR relaxation experiments.

Molecular motions are fundamental to the existence of life, and NMR spectroscopy remains one of the most useful and powerful methods to measure their rates and molecular characteristics. Multiple experimental methods are available for measuring the NMR relaxation properties and these can require different methods for extracting model parameters. We present here a new software application, RING NMR Dynamics, that is designed to support analysis of multiple relaxation types.

Assigning NMR spectra of RNA, peptides and small organic molecules using molecular network visualization software.

NMR assignment typically involves analysis of peaks across multiple NMR spectra. Chemical shifts of peaks are measured before being assigned to atoms using a variety of methods. These approaches quickly become complicated by overlap, ambiguity, and the complexity of correlating assignments among multiple spectra.

From Raw Data to Protein Backbone Chemical Shifts Using NMRFx Processing and NMRViewJ Analysis.

Assignment of the chemical shifts of the backbone atoms (HN, N, CA, CB, and C) of proteins is often a prerequisite to using NMR information in the study of proteins. These chemical shifts and their perturbations are the basis for the analysis of protein dynamics, ligand binding, and backbone conformation. They are generally assigned prior to full side-chain assignments and the determination of the complete three-dimensional molecular structure.

Combining asymmetric 13C-labeling and isotopic filter/edit NOESY: a novel strategy for rapid and logical RNA resonance assignment.

Although ∼98% of the human genomic output is transcribed as non-protein coding RNA, <2% of the protein data bank structures comprise RNA. This huge structural disparity stems from combined difficulties of crystallizing RNA for X-ray crystallography along with extensive chemical shift overlap and broadened linewidths associated with NMR of RNA. While half of the deposited RNA structures in the PDB were solved by NMR methods, the usefulness of NMR is still limited by the high cost of sample preparation and challenges of resonance assignment.

Maintenance Belatacept-Based Immunosuppression in Lung Transplantation Recipients Who Failed Calcineurin Inhibitors.

Background: Traditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lacks data in lung transplantation. This series aims to describe the response to belatacept ISR in 11 lung transplantation recipients after CNI failure.

Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation.

Refractory acute cellular rejection (rACR) is associated with death and bronchiolitis obliterans syndrome (BOS) post-lung transplantation. We report the largest cohort of lung transplant recipients (LTRs) treated with rescue alemtuzumab for rACR or BOS. RACR outcomes included burden of ACR 30 days before and 180 days after rescue assessed by a novel composite rejection standardized score (CRSS, range 0-6) and freedom from ≥A2 ACR.

NMRFx Processor: a cross-platform NMR data processing program.

NMRFx Processor is a new program for the processing of NMR data. Written in the Java programming language, NMRFx Processor is a cross-platform application and runs on Linux, Mac OS X and Windows operating systems. The application can be run in both a graphical user interface (GUI) mode and from the command line.

Surgical Strategy for Lung Transplantation in Adults With Small Chests: Lobar Transplant Versus a Pediatric Donor.

Background: Adult lung transplant recipients with small chests have traditionally received lungs from pediatric donors, placing an additional strain on the already restricted pediatric donor pool. Performing lobar lung transplantation (LLT) can circumvent issues with donor-recipient size mismatch; however, LLT imparts additional risks. Here, we review our experience using LLT and standard lung transplantation using a pediatric donor (PDLT) for adults with small chests.

Lung Transplant in Patients with Scleroderma Compared with Pulmonary Fibrosis. Short- and Long-Term Outcomes.

Rationale: Patients with advanced lung disease due to systemic sclerosis have long been considered suboptimal and often unacceptable candidates for lung transplant.

Objectives: To examine post-lung transplant survival of patients with systemic sclerosis compared with patients with pulmonary fibrosis and to identify risk factors for 1-year mortality.

Methods: In a retrospective cohort study, we compared post-lung transplant outcomes of 72 patients with scleroderma with those of 311 patients with pulmonary fibrosis between June 2005 and September 2013 at our institution.

Chemo-enzymatic synthesis of site-specific isotopically labeled nucleotides for use in NMR resonance assignment, dynamics and structural characterizations.

Stable isotope labeling is central to NMR studies of nucleic acids. Development of methods that incorporate labels at specific atomic positions within each nucleotide promises to expand the size range of RNAs that can be studied by NMR. Using recombinantly expressed enzymes and chemically synthesized ribose and nucleobase, we have developed an inexpensive, rapid chemo-enzymatic method to label ATP and GTP site specifically and in high yields of up to 90%.

Prediction of hydrogen and carbon chemical shifts from RNA using database mining and support vector regression.

The Biological Magnetic Resonance Data Bank (BMRB) contains NMR chemical shift depositions for over 200 RNAs and RNA-containing complexes. We have analyzed the (1)H NMR and (13)C chemical shifts reported for non-exchangeable protons of 187 of these RNAs. Software was developed that downloads BMRB datasets and corresponding PDB structure files, and then generates residue-specific attributes based on the calculated secondary structure.

RNA structure. Structure of the HIV-1 RNA packaging signal.

The 5' leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. By using a (2)H-edited nuclear magnetic resonance (NMR) approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (core encapsidation signal; Ψ(CES)). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions.

First successful lung transplantation for sickle cell disease with severe pulmonary arterial hypertension and pulmonary veno-occlusive disease.

Little is known about the use of lung transplantation in the management of sickle cell disease-associated pulmonary arterial hypertension (SCD-PAH). We present clinical and pathological data and report the first successful outcome of bilateral lung transplantation in a patient with severe SCD-PAH and pulmonary veno-occlusive disease (PVOD). We discuss the complexities of multidisciplinary planning and management of lung transplantation in patients with SCD-associated pulmonary vascular complications.

Database proton NMR chemical shifts for RNA signal assignment and validation.

The Biological Magnetic Resonance Data Bank contains NMR chemical shift depositions for 132 RNAs and RNA-containing complexes. We have analyzed the (1)H NMR chemical shifts reported for non-exchangeable protons of residues that reside within A-form helical regions of these RNAs. The analysis focused on the central base pair within a stretch of three adjacent base pairs (BP triplets), and included both Watson-Crick (WC; G:C, A:U) and G:U wobble pairs.

Ligand and receptor dynamics contribute to the mechanism of graded PPARγ agonism.

Ligand binding to proteins is not a static process, but rather involves a number of complex dynamic transitions. A flexible ligand can change conformation upon binding its target. The conformation and dynamics of a protein can change to facilitate ligand binding.

Changing practice paradigms: negotiating your future.

There are many recent and ongoing changes in the practice of medicine from a business standpoint as well as in overall practice management. Economic and lifestyle desires have pushed many physicians to a decision point of whether or not to join a large multispecialty group or to sell their practice and become an employee of a hospital system. There are advantages and disadvantages to both options; however, deciding on the most appropriate path for each individual can be a daunting task.

Accountable care organizations and beyond. Position your practice for a quality-based delivery system.

Practices have already begun the process of bridging the gap between volume-based payment structures and quality-focused systems. Industry experts provide tips on ways professionals can shift cultural mindsets by using existing data to engage in analysis, assessment and improvement processes.

Physician-hospital integration: making it work.

This article discusses the driving forces for physician-hospital integration and details a range of structural integration models available to physicians and hospitals as they seek heightened collaboration. The structural model that is the "best fit" for an organization will depend on articulated goals, current stage of integration, available legal alternatives, "local" and cultural considerations, history of the parties, and other key variables. The importance of physician leadership and engagement, broadening Board members' perspectives, and other similar strategies adopted by high-performing integrated systems are reported.