Structural Snapshots, Trajectory and Thermodynamics of the Reversible μ-1,2-Peroxo/μ-1,1-Hydroperoxo Dicopper(II) Interconversion.

Hydrogen bonds involving the oxygen atoms of intermediates that result from copper-mediated O activation play a key role for controlling the reactivity of Cu/O active sites in metalloenzymes and synthetic model complexes. However, structural insight into H-bonding in such transient species as well as thermodynamic information about proton transfer to or from the O-derived ligands is scarce. Here we present a detailed study of the reversible interconversion of a μ-peroxodicopper(II) complex ([1]) and its μ-hydroperoxo congener ([2]) via (de)protonation, including the isolation and structural characterization of several H-bond donor (HBD) adducts of [1] and the determination of binding constants.

Expanding the Clip-and-Cleave Concept: Approaching Enantioselective C-H Hydroxylations by Copper Imine Complexes Using O and HO as Oxidants.

Copper-mediated aromatic and aliphatic C-H hydroxylations using benign oxidants (O and HO) have been studied intensively in recent years to meet the growing demand for efficient and green C-H functionalizations. Herein, we report an enantioselective variant of the so-called clip-and-cleave concept for intramolecular ligand hydroxylations by the application of chiral diamines as directing groups. We tested the hydroxylation of cyclohexanone and 1-acetyladamantane under different oxidative conditions (Cu/O; Cu/HO; Cu/HO) in various solvents.

The Impact of Second-Shell Nucleotides on Ligand Specificity in Cyclic Dinucleotide Riboswitches.

Ligand specificity is an essential requirement for all riboswitches. Some variant riboswitches utilize a common structural motif, yet through subtle sequence differences, they are able to selectively respond to different small molecule ligands and regulate downstream gene expression. These variants discriminate between structurally and chemically similar ligands.

Translation regulation by a guanidine-II riboswitch is highly tunable in sensitivity, dynamic range, and apparent cooperativity.

Riboswitches function as important translational regulators in bacteria. Comprehensive mutational analysis of transcriptional riboswitches has been used to probe the energetic intricacies of interplay between the aptamer and expression platform, but translational riboswitches have been inaccessible to massively parallel techniques. The guanidine-II (gdm-II) riboswitch is an exclusively translational class.

How Do Bacteria "See" Molecules Inside Themselves?

RNA, like its close cousin DNA, is used to store information in the cell. Unlike DNA, it is really good at folding up into interesting shapes, which makes it good at lots of other important jobs. Some kinds of RNA, called riboswitches, can sense what is going on inside a cell.

Dynamic Response of Donor-Derived Cell-Free DNA Following Treatment of Acute Rejection in Kidney Allografts.

Background: The quantification of rejection treatment efficacy has been insufficient using traditional markers due, in part, to the lagging response of serum creatinine and histologic alterations on biopsy specimens. Donor-derived cell-free DNA (dd-cfDNA) is a molecular marker of injury that may assess allograft injury after rejection.

Methods: Retrospective review of the DART study identified 70 patients who had a clinically indicated biopsy, simultaneous dd-cfDNA measurement, and at least one follow-up dd-cfDNA within 3 months post-treatment.

The Positively Charged Active Site of the Bacterial Toxin RelE Causes a Large Shift in the General Base p.

The bacterial toxin RelE cleaves mRNA in the ribosomal A site. Although it shares a global fold with other microbial RNases, the active site contains several positively charged residues instead of histidines and glutamates that are typical of ribonucleases. The pH dependences of wild-type and mutant RelE indicate it uses general acid-base catalysis, but either the general acid (proposed to be R81) or the general base must have a substantially downshifted p.

The asymmetry and cooperativity of tandem glycine riboswitch aptamers.

Glycine riboswitches utilize both single- and tandem-aptamer architectures. In the tandem system, the relative contribution of each aptamer toward gene regulation is not well understood. To dissect these contributions, the effects of 684 single mutants of a tandem ON switch from were characterized for the wild-type construct and binding site mutations that selectively restrict ligand binding to either the first or second aptamer.

Gene expression profiling and racial disparities in outcomes after heart transplantation.

Background: African Americans (AAs) have lower survival rates after heart transplantation (HTx) than Caucasians. The aim of this analysis was to evaluate racial differences in gene expression and their associations with survival and the composite outcome of death, retransplant, rejection with hemodynamic compromise, and graft dysfunction in the Outcomes AlloMap Registry.

Methods: Registry participants included low-risk Caucasian and AA heart transplant recipients with a baseline and at least 1 follow-up gene expression test (AlloMap(C)) within the first year after HTx.

Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study.

Standardized donor-derived cell-free DNA (dd-cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd-cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single-center cohort of 33 patients at high risk for antibody-mediated rejection (AMR).

Consequences of Increasing Complexity in Anorectal Surgery Performed at an Academic Center.

Background: Anorectal surgery encompasses a wide range of procedures with varying complexity. The Accreditation Council for Graduate Medical Education Review Committee for Colon and Rectal Surgery recommends minimum case numbers (60) for 1-year specialty trainees in 6 categories of anorectal surgery, with definitions for procedural complexity.

Objective: The purpose of this study was to assess the scope of anorectal procedures and propose a stratification of procedures based on a consensus of levels of difficulty, as well as to identify a predictive charge cutoff suggestive of procedural complexity.

Gene regulation by a glycine riboswitch singlet uses a finely tuned energetic landscape for helical switching.

Riboswitches contain structured aptamer domains that, upon ligand binding, facilitate helical switching in their downstream expression platforms to alter gene expression. To fully dissect how riboswitches function requires a better understanding of the energetic landscape for helical switching. Here, we report a sequencing-based high-throughput assay for monitoring in vitro transcription termination and use it to simultaneously characterize the functional effects of all 522 single point mutants of a glycine riboswitch type-1 singlet.

Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor Specific Antibody Positive Kidney Transplant Recipients.

Background: Elevated levels of donor-derived cell-free DNA (dd-cfDNA) in the plasma of renal allograft recipients indicates organ injury and an increased probability of active rejection. Donor-specific antibodies (DSA) to HLA antigens are associated with risk of antibody-mediated rejection (ABMR). This study assessed the combined use of dd-cfDNA and DSA testing to diagnose active ABMR.

Robotic Rectopexy for Rectal Prolapse in Pediatric Patients.

Rectal prolapse is the protrusion of the rectum out of the anus. Surgical correction can be accomplished via open and minimally invasive abdominal approaches, as well as from the perineum. Robotic rectopexy is an option for minimally invasive treatment of rectal prolapse.

Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications.

Background: Previous studies have demonstrated that donor-derived cell-free DNA (dd-cfDNA) found in circulating blood of transplant recipients may serve as a noninvasive biomarker of allograft rejection. To better interpret the clinical meaning of dd-cfDNA, it is essential to understand the biological variation of this biomarker in stable healthy recipients. This report establishes the biological variation and clinical reference intervals of dd-cfDNA in renal transplant recipients by using an analytically validated assay that has a CV of 6.

Mycofumigation through production of the volatile DNA-methylating agent -methyl--nitrosoisobutyramide by fungi in the genus .

Antagonistic microorganisms produce antimicrobials to inhibit the growth of competitors. Although water-soluble antimicrobials are limited to proximal interactions via aqueous diffusion, volatile antimicrobials are able to act at a distance and diffuse through heterogeneous environments. Here, we identify the mechanism of action of , an endophytic fungus known for its volatile antimicrobial activity toward a wide range of human and plant pathogens and its potential use in mycofumigation.

Cell-Free DNA and Active Rejection in Kidney Allografts.

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies.

Validation of a Clinical-Grade Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients.

The use of circulating cell-free DNA (cfDNA) as a biomarker in transplant recipients offers advantages over invasive tissue biopsy as a quantitative measure for detection of transplant rejection and immunosuppression optimization. However, the fraction of donor-derived cfDNA (dd-cfDNA) in transplant recipient plasma is low and challenging to quantify. Previously reported methods to measure dd-cfDNA require donor and recipient genotyping, which is impractical in clinical settings and adds cost.

Depressive symptoms in older long-term colorectal cancer survivors: a population-based analysis using the SEER-Medicare healthcare outcomes survey.

Purpose: Colorectal cancer survivorship has improved significantly over the last 20 years; however, few studies have evaluated depression among older colorectal cancer survivors, especially using a population-based sample. The aim of this study was to identify correlates for positive depression screen among colorectal cancer survivors who underwent potentially curative surgery.

Methods: Using the 1998-2007 Surveillance, Epidemiology, and End-Result registry and the Medicare Health Outcome Survey linked dataset, we identified patients over 65 with pathology confirmed and resected colorectal cancer enrolled in Medicare.

Incidence and Operative Excision of Presacral Masses: An Institutional Analysis.

Presacral masses are rare lesions that encompass a broad range of pathologic findings. Most presacral masses are benign. The aim of this study was to analyze the clinical presentation, pathology, and surgical treatment of presacral masses at a single academic institution over a decade.

Transition State Charge Stabilization and Acid-Base Catalysis of mRNA Cleavage by the Endoribonuclease RelE.

The bacterial toxin RelE is a ribosome-dependent endoribonuclease. It is part of a type II toxin-antitoxin system that contributes to antibiotic resistance and biofilm formation. During amino acid starvation, RelE cleaves mRNA in the ribosomal A-site, globally inhibiting protein translation.