Breathless nights and heart flutters: Understanding the relationship between obstructive sleep apnea and atrial fibrillation.

There is an extraordinary and increasing global burden of atrial fibrillation (AF) and obstructive sleep apnea (OSA), two conditions that frequently accompany one another and that share underlying risk factors. Whether a causal pathophysiologic relationship connects OSA to the development and/or progression of AF, or whether shared risk factors promote both conditions, is unproven. With increasing recognition of the importance of controlling AF-related risk factors, numerous observational studies now highlight the potential benefits of OSA treatment in AF-related outcomes.

Evaluation of obstructive sleep apnea among consecutive patients with all patterns of atrial fibrillation using WatchPAT home sleep testing.

Background: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and is associated with significant morbidity, mortality, and financial burden. Obstructive sleep apnea (OSA) is more common in individuals with AF and may impair the efficacy of rhythm control strategies including catheter ablation. However, the prevalence of undiagnosed OSA in all-comers with AF is unknown.

Ribosomopathies: There's strength in numbers.

Ribosomopathies are a group of human disorders most commonly caused by ribosomal protein haploinsufficiency or defects in ribosome biogenesis. These conditions manifest themselves as physiological defects in specific cell and tissue types. We review current molecular models to explain ribosomopathies and attempt to reconcile the tissue specificity of these disorders with the ubiquitous requirement for ribosomes in all cells.

Encouraging Critical Clinical Thinking (CCT) Skills in First-Year Veterinary Students.

First-year didactic course instructors at the University of Illinois College of Veterinary Medicine leverage earlier clinical rotation experiences with weekly "Clinical Correlations" exercises to provide early exposure to critical clinical thinking (CCT). This study evaluated the efficacy of individual and paired group exercises on CCT development. Before and after instruction, the Cornell Critical Thinking Test (Level Z) (CCTTZ) was administered.

Case of Secondary Tics Associated With Olanzapine in an Adult.

Atypical antipsychotic medications, such as risperidone, aripiprazole, and olanzapine, have utility in treating motor tics, particularly in Tourette syndrome. In rare cases, atypical antipsychotic medications have been associated with adult-onset motor tics. Such adverse drug reactions have been documented in response to quetiapine, aripiprazole, and amisulpride.

Slowed decay of mRNAs enhances platelet specific translation.

Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of messenger RNAs (mRNAs), ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA sequencing (RNA-Seq) and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro-derived MK cells and that these platelet-enriched transcripts are broadly occupied by ribosomes.

Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets.

Protein synthesis continues in platelets and maturing reticulocytes, although these blood cells lack nuclei and do not make new mRNA or ribosomes. Here, we analyze translation in primary human cells from anucleate lineages by ribosome profiling and uncover a dramatic accumulation of post-termination unrecycled ribosomes in the 3' UTRs of mRNAs. We demonstrate that these ribosomes accumulate as a result of the natural loss of the ribosome recycling factor ABCE1 during terminal differentiation.

Non-Patient-Based Clinical Licensure Examination for Dentistry in Minnesota: Significance of Decision and Description of Process.

In recent years in the United States, there has been heightened interest in offering clinical licensure examination (CLE) alternatives to the live patient-based method in dentistry. Fueled by ethical concerns of faculty members at the University of Minnesota School of Dentistry, the state of Minnesota's Board of Dentistry approved a motion in 2009 to provide two CLE options to the school's future predoctoral graduates: a patient-based one, administered by the Central Regional Dental Testing Service, and a non-patient-based one administered by the National Dental Examining Board of Canada (NDEB). The validity of the NDEB written exam and objective structured clinical exam (OSCE) has been verified in a multi-year study.

Protein Transfer Free Energy Obeys Entropy-Enthalpy Compensation.

We have found significant entropy-enthalpy compensation for the transfer of a diverse set of two-state folding proteins from water into water containing a diverse set of cosolutes, including osmolytes, denaturants, and crowders. In extracting thermodynamic parameters from experimental data, we show the potential importance of accounting for the cosolute concentration-dependence of the heat capacity change upon unfolding, as well as the potential importance of the temperature-dependence of the heat capacity change upon unfolding. We introduce a new Monte Carlo method to estimate the experimental uncertainty in the thermodynamic data and use this to show by bootstrapping methods that entropy-enthalpy compensation is statistically significant, in spite of large, correlated scatter in the data.

An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration.

Downregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly reported in colon cancer and other epithelial tumors. In addition, overexpression of these miRNAs inhibits tumorigenesis, leading to broad consensus that they function as cell-autonomous epithelial tumor suppressors. We generated mice with deletion of miR-143/145 to investigate the functions of these miRNAs in intestinal physiology and disease in vivo.

A bicistronic MAVS transcript highlights a class of truncated variants in antiviral immunity.

Bacterial and viral mRNAs are often polycistronic. Akin to alternative splicing, alternative translation of polycistronic messages is a mechanism to generate protein diversity and regulate gene function. Although a few examples exist, the use of polycistronic messages in mammalian cells is not widely appreciated.

Density functional theory for protein transfer free energy.

We cast the problem of protein transfer free energy within the formalism of density functional theory (DFT), treating the protein as a source of external potential that acts upon the solvent. Solvent excluded volume, solvent-accessible surface area, and temperature dependence of the transfer free energy all emerge naturally within this formalism, and may be compared with simplified "back of the envelope" models, which are also developed here. Depletion contributions to osmolyte induced stability range from 5 to 10 kBT for typical protein lengths.

Dental students choosing licensure path give more consideration to career flexibility rather than ethical dilemmas.

Although a patient-based clinical licensure examination (CLE) has been used in the United States for many decades to evaluate an individual's competency to practice dentistry, there continue to be validity, reliability, and ethical issues of concern to the profession. As a result of a 2009 decision by the Minnesota Board of Dentistry, dental students from the University of Minnesota School of Dentistry, beginning with the Class of 2010, are eligible for initial licensure in Minnesota by passing the nonpatient-based National Dental Examining Board of Canada Examination. Surveys were distributed to 101 senior dental students to assess what factors students used to decide whether or not to register for a patient-based CLE.

Dependence on a retinophilin/myosin complex for stability of PKC and INAD and termination of phototransduction.

Normal termination of signaling is essential to reset signaling cascades, especially those such as phototransduction that are turned on and off with great rapidity. Genetic approaches in Drosophila led to the identification of several proteins required for termination, including protein kinase C (PKC), NINAC (neither inactivation nor afterpotential C) p174, which consists of fused protein kinase and myosin domains, and a PDZ (postsynaptic density-95/Discs Large/zona occludens-1) scaffold protein, INAD (inactivation no afterpotential D). Here, we describe a mutation affecting a poorly characterized but evolutionarily conserved protein, Retinophilin (Retin), which is expressed primarily in the phototransducing compartment of photoreceptor cells, the rhabdomeres.

Mechanisms of brain iron transport: insight into neurodegeneration and CNS disorders.

Trace metals such as iron, copper, zinc, manganese, and cobalt are essential cofactors for many cellular enzymes. Extensive research on iron, the most abundant transition metal in biology, has contributed to an increased understanding of the molecular machinery involved in maintaining its homeostasis in mammalian peripheral tissues. However, the cellular and intercellular iron transport mechanisms in the central nervous system (CNS) are still poorly understood.

Activating mutations of the TRPML1 channel revealed by proline-scanning mutagenesis.

The mucolipin TRP (TRPML) proteins are a family of endolysosomal cation channels with genetically established importance in humans and rodent. Mutations of human TRPML1 cause type IV mucolipidosis, a devastating pediatric neurodegenerative disease. Our recent electrophysiological studies revealed that, although a TRPML1-mediated current can only be recorded in late endosome and lysosome (LEL) using the lysosome patch clamp technique, a proline substitution in TRPML1 (TRPML1(V432P)) results in a large whole cell current.

Peer assessment of a final-year capstone experience for formative evaluation of a pathology curriculum.

In spring of 2005, the authors implemented and evaluated a process at the Iowa State University College of Veterinary Medicine in which third-year students evaluated fourth-year students' performances on an advanced case-analysis assignment. This assignment, called the case correlation assignment, required a thorough integration and explanation of all ante- and post-mortem data for a specific hospital patient. Using a 21-point rubric, the necropsy course instructor and third-year students rated these assignments.

The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel.

TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients have motor impairment, mental retardation, retinal degeneration and iron-deficiency anaemia.

Mechanism-based diagnostic reasoning: thoughts on teaching introductory clinical pathology.

Teaching introductory clinical pathology to veterinary students is a challenging endeavor that requires a shift in learning strategies from rote memorization to diagnostic reasoning. Educational research has identified discrete cognitive stages required to achieve the automated, unconscious thinking process used by experts. Building on this knowledge, we developed a case-based approach to clinical pathology instruction that actively engages students in the learning process and links performance with positive reward.