Vernakalant: a new drug to treat patients with acute onset atrial fibrillation.

Vernakalant is a new antiarrhythmic drug that acts selectively in the atrium, targeting atrial specific channels: the Kv1.5 channel which carries IK(ur), and the Kir3.1/3.

Papillary urothelial hyperplasia: relationship to urothelial neoplasms.

Aims: The current study assessed the prognosis of papillary urothelial hyperplasia as its significance is uncertain due to limited studies on this topic.

Methods: 53 patients with papillary urothelial hyperplasia were identified from the files of the senior author.

Results: There were 40 males and 13 females with ages ranging from 46 to 101 years (median 74 years).

TbPIF1, a Trypanosoma brucei mitochondrial DNA helicase, is essential for kinetoplast minicircle replication.

Kinetoplast DNA, the trypanosome mitochondrial genome, is a network of interlocked DNA rings including several thousand minicircles and a few dozen maxicircles. Minicircles replicate after release from the network, and their progeny reattach. Remarkably, trypanosomes have six mitochondrial DNA helicases related to yeast PIF1 helicase.

TbPIF5 is a Trypanosoma brucei mitochondrial DNA helicase involved in processing of minicircle Okazaki fragments.

Trypanosoma brucei's mitochondrial genome, kinetoplast DNA (kDNA), is a giant network of catenated DNA rings. The network consists of a few thousand 1 kb minicircles and several dozen 23 kb maxicircles. Here we report that TbPIF5, one of T.

Trypanosomes have six mitochondrial DNA helicases with one controlling kinetoplast maxicircle replication.

Kinetoplast DNA (kDNA), the trypanosome mitochondrial DNA, contains thousands of minicircles and dozens of maxicircles interlocked in a giant network. Remarkably, Trypanosoma brucei's genome encodes 8 PIF1-like helicases, 6 of which are mitochondrial. We now show that TbPIF2 is essential for maxicircle replication.

Cardiolipin, a critical determinant of mitochondrial carrier protein assembly and function.

The ability of phospholipids to act as determinants of membrane protein structure and function is probably best exemplified by cardiolipin (CL), the signature phospholipid of mitochondria. Early efforts to reconstitute individual respiratory complexes and members of the mitochondrial carrier family, most notably the ADP/ATP carrier (AAC), often demonstrated the importance of CL. Over the past decade, the significance of CL in the organization of components of the electron transport chain into higher order assemblies, termed respiratory supercomplexes, has been established.

A new function of Trypanosoma brucei mitochondrial topoisomerase II is to maintain kinetoplast DNA network topology.

The mitochondrial genome of Trypanosoma brucei, called kinetoplast DNA, is a network of topologically interlocked DNA rings including several thousand minicircles and a few dozen maxicircles. Kinetoplast DNA synthesis involves release of minicircles from the network, replication of the free minicircles and reattachment of the progeny. Here we report a new function of the mitochondrial topoisomerase II (TbTOP2mt).

What happens when Trypanosoma brucei leaves Africa.

Julius Lukes and co-workers evaluated the evolutionary origin of Trypanosoma equiperdum and Trypanosoma evansi, parasites that cause horse and camel diseases. Although similar to T. brucei, the sleeping-sickness parasite, these trypanosomes do not cycle through the tsetse fly and have been able to spread beyond Africa.

Cysteine scanning mutagenesis of TM5 reveals conformational changes in OxlT, the oxalate transporter of Oxalobacter formigenes.

We constructed a single-cysteine panel encompassing TM5 of the oxalate transporter, OxlT. The 25 positions encompassed by TM5 were largely tolerant of mutagenesis, and functional product was recovered for 21 of the derived variants. For these derivatives, thiol-directed MTS-linked agents (MTSEA, MTSCE, and MTSES) were used as probes of transporter function, yielding 11 mutants that responded to probe treatment, as indicated by effects on oxalate transport.

Elbow and shoulder lesions of baseball players : George E. Bennett MD (1885-1962). The 8th president of the AAOS 1939.

George Eli Bennett was born in Claryville, NY, in the Catskill Mountains, in 1885 [3]. His parents both died by the time he was 11, leaving him the need to work while going to school, but he excelled in school and sports. He played semipro baseball at the age of 16.

p166, a link between the trypanosome mitochondrial DNA and flagellum, mediates genome segregation.

Kinetoplast DNA (kDNA), the trypanosome mitochondrial genome, is a giant network containing several thousand interlocked DNA rings. Within the mitochondrion, kDNA is condensed into a disk-shaped structure positioned near the flagellar basal body. The disk is linked to the basal body by a remarkable transmembrane filament system named the tripartite attachment complex (TAC).

Reducing the risk of mother-to-child human immunodeficiency virus transmission: past successes, current progress and challenges, and future directions.

Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) in the United States and Europe has been a tremendous success, such that transmission rates of less than 2% have been achieved. Some key successes have also been demonstrated in resource-poor countries; however, the translation of successful interventions into public health policy has been slow because of a variety of factors such as inadequate funding and cultural, social, and institutional barriers. The issue of HIV and infant feeding in settings that lack culturally acceptable, feasible, affordable, safe, and sustainable nutritional substitutes for breast milk is a continuing dilemma.

Enzymatic capture of an extrahelical thymine in the search for uracil in DNA.

The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism. Efficient removal of uracil is essential for prevention of C-to-T transition mutations arising from cytosine deamination, cytotoxic U*A pairs arising from incorporation of dUTP in DNA, and for increasing immunoglobulin gene diversity during the acquired immune response. A central event in all of these UNG-mediated processes is the singling out of rare U*A or U*G base pairs in a background of approximately 10(9) T*A or C*G base pairs in the human genome.

The rotational dynamics of kinetoplast DNA replication.

Kinetoplast DNA (kDNA), from trypanosomatid mitochondria, is a network containing several thousand catenated minicircles that is condensed into a disk-shaped structure in vivo. kDNA synthesis involves release of individual minicircles from the network, replication of the free minicircles and reattachment of progeny at two sites on the network periphery approximately 180 degrees apart. In Crithidia fasciculata, rotation of the kDNA disk relative to the antipodal attachment sites results in distribution of progeny minicircles in a ring around the network periphery.

Multivariate analysis and visualization of splicing correlations in single-gene transcriptomes.

Background: RNA metabolism, through 'combinatorial splicing', can generate enormous structural diversity in the proteome. Alternative domains may interact, however, with unpredictable phenotypic consequences, necessitating integrated RNA-level regulation of molecular composition. Splicing correlations within transcripts of single genes provide valuable clues to functional relationships among molecular domains as well as genomic targets for higher-order splicing regulation.

Genomics of sleep-disordered breathing.

The technologies of genomics and proteomics are powerful tools for discovering novel gene and protein expression responses to disease. Considerable evidence indicates that a genetic basis exists to the causes of sleep-disordered breathing, in particular its most common form of obstructive sleep apnea (OSA), which is characterized by periods of intermittent hypoxia and disrupted sleep. However, the genetic contribution to the pathogenesis of OSA has largely been determined using traditional genetic approaches of family, twin, and linkage studies in clinical populations and quantitative trait loci and targeted gene procedures in animal models of OSA.

Fatty acid synthesis by elongases in trypanosomes.

All eukaryotic and prokaryotic organisms are thought to synthesize fatty acids using a type I or type II synthase. In addition, eukaryotes extend pre-existing long chain fatty acids using microsomal elongases (ELOs). We have found that Trypanosoma brucei, a eukaryotic human parasite that causes sleeping sickness, uses three elongases instead of type I or type II synthases for the synthesis of nearly all its fatty acids.

Analysis of substrate-binding elements in OxlT, the oxalate:formate antiporter of Oxalobacter formigenes.

An OxlT homology model suggests R272 and K355 in transmembrane helices 8 and 11, respectively, are critical to OxlT-mediated transport. We offer positive evidence supporting this idea by studying OxlT function after cysteine residues were separately introduced at these positions. Without further treatment, both mutant proteins had a null phenotype when they were reconstituted into proteoliposomes.

Effects of morphine on circadian rhythms of motor activity and body temperature in pig-tailed macaques.

Previous studies of the effects of opiates on motor activity and body temperature in nonhuman primates have been limited in scope and typically only conducted with restrained animals. The present study used radio-telemetry devices to continuously measure activity and temperature in unrestrained pig-tailed macaques for 24 h following morphine administration. Two dose-response functions (0.