Clonal, self-renewing and differentiating human and porcine urothelial cells, a novel stem cell population.

Although urothelial progenitor-like cells have been described in the human urinary tract, the existence of stem cells remains to be proven. Using a culture system that favors clonogenic epithelial cell growth, we evaluated and characterized clonal human urothelial cells. We isolated human urothelial cells that were clonogenic, capable of self-renewal and could develop into fully differentiated urothelium once re-implanted into the subcapsular space of nude mice. In addition to final urothelial cell differentiation, spontaneous formation of bladder-like microstructures was observed. By examining an epithelial stem cell signature marker, we found p63 to correlate with the self-renewal capacity of the isolated human urothelial clonal populations. Since a clinically relevant, long-term model for functional reconstitution of human cells does not exist, we sought to establish a culture method for porcine urothelial cells in a clinically relevant porcine model. We isolated cells from porcine ureter, urethra and bladder that were clonogenic and capable of self-renewal and differentiation into fully mature urothelium. In conclusion, we could isolate human and porcine cell populations, behaving as urothelial stem cells and showing clonogenicity, self-renewal and, once re-implanted, morphological differentiation.

Changes in leg-spring behavior during a 5000 m self-paced run in differently trained athletes

Summary Aims.-To explore whether fatigue-induced changes in spring-mass behavior during a 5000m self-paced run varied according to the runner's training status. Methods and results.-Six highly- and six well-trained triathletes completed a 5000m time trial. Running velocity and vertical stiffness decreased significantly (P < 0.05) with fatigue, whereas leg stiffness remained constant. None of these parameters displayed a significant interaction between fatigue and training status, despite vertical stiffness being higher (P < 0.05) in highly-trained triathletes. Conclusions.-During a 5000m self-paced run, impairments in leg-spring behavior that occur with fatigue are not affected by athletes' training status. © 2009 Elsevier Masson SAS. All rights reserved. Objectifs.-Étudier, chez des athlètes de niveaux différents, les modifications de raideur mécanique liées à l'apparition de la fatigue lors d'une course de 5000 m. Synthèse des faits.-Six triathlètes très entraînés et six autres bien entraînés ont réalisé une course de 5000 m. La vitesse de course et la raideur verticale diminuaient significativement (p < 0,05) avec la fatigue, alors que la raideur de la jambe demeurait inchangée. Aucune interaction entre la fatigue et le niveau d'entraînement n'a été détectée, malgré des niveaux de raideur verticale plus élevés (p < 0,05) chez les sujets les mieux entraînés.

NS4B Self-Interaction through Conserved C-Terminal Elements Is Required for the Establishment of Functional Hepatitis C Virus Replication Complexes.

Hepatitis C virus (HCV) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. Studies of the HCV life cycle have become possible with the development of cell culture systems supporting the replication of viral RNA and the production of infectious virus. However, the exact functions of individual proteins, especially of nonstructural protein 4B (NS4B), remain poorly understood. NS4B triggers the formation of specific, vesicular membrane rearrangements, referred to as membranous webs, which have been reported to represent sites of HCV RNA replication. However, the mechanism of vesicle induction is not known. In this study, a panel of 15 mutants carrying substitutions in the highly conserved NS4B C-terminal domain was generated. Five mutations had only a minor effect on replication, but two of them enhanced assembly and release of infectious virus. Ten mutants were replication defective and used for selection of pseudoreversions. Most of the pseudoreversions also localized to the highly conserved NS4B C-terminal domain and were found to restore replication competence upon insertion into the corresponding primary mutant. Importantly, pseudoreversions restoring replication competence also restored heterotypic NS4B self-interaction, which was disrupted by the primary mutation. Finally, electron microscopy analyses of membrane alterations induced by NS4B mutants revealed striking morphological abnormalities, which were restored to wild-type morphology by the corresponding pseudoreversion. These findings demonstrate the important role of the C-terminal domain in NS4B self-interaction and the formation of functional HCV replication complexes.

Iowa's Leadership in Research and Development, 2010

Pentagon-classified navigation systems are designed and tested. Genetically-superior, drought resistant triple-stacked corn hybrids exponentially improve corn and soybean yields. Scientists discover a simple flower, the marigold, unlocks astonishing potential as a change agent to improve the world’s health. All achieved or discovered in Iowa, the common denominator among all of these extraordinary activities is the intensive research and development efforts involved in bringing them to market. For businesses heavily dependent on research and development, one of their strategic advantages of conducting that world-changing research in Iowa is the state’s Research Activities Credit, commonly referred to as the Research and Development tax credit. Whether a company’s specific strategy is planting a stake into emerging markets, expanding its market leadership position, or paving technological inroads to gain market share, the success of those efforts is largely dependent on the company’s preceding work in research and development. Iowa recognizes how significant these resulting innovations are to long-term business growth and stability. Even though the federal research credits have fluctuated with intermittent expiration dates and reinstatement periods, Iowa has remained consistent in its support for the Research Activities Credit over theyears.

Genesis of self-organized zebra textures in burial dolomites: Displacive veins, induced stress, and dolomitization

The dolomite veins making up rhythmites common in burial dolomites are not cement infillings of supposed cavities, as in the prevailing view, but are instead displacive veins, veins that pushed aside the host dolostone as they grew. Evidence that the veins are displacive includes a) small transform-fault-like displacements that could not have taken place if the veins were passive cements, and b) stylolites in host rock that formed as the veins grew in order to compensate for the volume added by the veins. Each zebra vein consists of crystals that grow inward from both sides, and displaces its walls via the local induced stress generated by the crystal growth itself. The petrographic criterion used in recent literature to interpret zebra veins in dolomites as cements - namely, that euhedral crystals can grow only in a prior void - disregards evidence to the contrary. The idea that flat voids did form in dolostones is incompatible with the observed optical continuity between the saddle dolomite euhedra of a vein and the replacive dolomite crystals of the host. The induced stress is also the key to the self-organization of zebra veins: In a set of many incipient, randomly-spaced, parallel veins just starting to grow in a host dolostone, each vein¿s induced stress prevents too-close neighbor veins from nucleating, or redissolves them by pressure-solution. The veins that survive this triage are those just outside their neighbors¿s induced stress haloes, now forming a set of equidistant veins, as observed.

Gas identification with tin oxide sensor array and self-organizing maps: adaptive correction of sensor drifts

Low-cost tin oxide gas sensors are inherently nonspecific. In addition, they have several undesirable characteristics such as slow response, nonlinearities, and long-term drifts. This paper shows that the combination of a gas-sensor array together with self-organizing maps (SOM's) permit success in gas classification problems. The system is able to determine the gas present in an atmosphere with error rates lower than 3%. Correction of the sensor's drift with an adaptive SOM has also been investigated