Synthesis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPgammaS-dependent activator of PI(4)P5Kalpha is the small G protein ADP-ribosylation factor (ARF) and that the activation strictly requires phosphatidic acid, the product of phospholipase D (PLD). In vivo, ARF6, but not ARF1 or ARF5, spatially coincides with PI(4)P5Kalpha. This colocalization occurs in ruffling membranes formed upon AIF4 and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cdelta1, indicating locally elevated PI(4,5)P2. Thus, PI(4)P5Kalpha is a downstream effector of ARF6 and when ARF6 is activated by agonist stimulation, it triggers recruitment of a diverse but interactive set of signaling molecules into sites of active cytoskeletal and membrane rearrangement.

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normalLi2MnnormalO3 is shown to be electrochemically active, with a maximum charge capacity of ∼350mAh∕g and a discharge capacity of ∼260mAh∕g at 25°C . A total of 1mole of Li can be extracted from Li[Li1∕3Mn2∕3]normalO2 , and the first cycle efficiency is ∼66% regardless of state of charge. Larger charge-discharge capacity is obtained from materials with smaller particle size and larger amount of stacking faults. Composition and structural analyses indicate that Li are removed from both the Li and transitional metal layers of the material during charging. Results from X-ray-absorption fine-structure measurements suggest that the valence of Mn remains at 4+ during charging but is reduced during discharging. Charging is accompanied by gas generation: at 25°C , oxygen is the main gas detected, and the total amount accounts for ∼1∕8mole of O2 generation from Li[Li1∕3Mn2∕3]normalO2 . At an elevated temperature, amount of CnormalO2 increases due to electrolyte decomposition. normalLi2MnnormalO3 shows poor cycle performance, which is attributed to phase transformation and low charge-discharge efficiency during cycling. Low first-cycle efficiency, gas generation, and poor cycle performance limit the usage of normalLi2MnnormalO3 in practical batteries.

No abstract

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.

The common cuckoo Cuculus canorus is divided into host-specific races (gentes). Females of each race lay a distinctive egg type that tends to match the host's eggs, for instance, brown and spotted for meadow pipit hosts or plain blue for redstart hosts. The puzzle is how these gentes remain distinct. Here, we provide genetic evidence that gentes are restricted to female lineages, with cross mating by males maintaining the common cuckoo genetically as one species. We show that there is differentiation between gentes in maternally inherited mitochondrial DNA, but not in microsatellite loci of nuclear DNA. This supports recent behavioural evidence that female, but not male, common cuckoos specialize on a particular host, and is consistent with the possibility that genes affecting cuckoo egg type are located on the female-specific W sex chromosome. Our results also support the ideas that common cuckoos often switched hosts during evolution, and that some gentes may have multiple, independent origins, due to colonization by separate ancestral lineages.

ACE angiotensin converting enzyme BAL bronchoalveolar lavage CRT cardiac resynchronization therapy CT computed tomography 18 F-FDG fluorine-18 fluorodeoxyglucose 67 Ga gallium-67 HRCT high resolution computed tomography ICD implantable cardioverter defibrillator MRI magnetic resonance imaging PET positron emission tomography sIL-2R soluble interleukin 2 recepter SPECT single photon emission computed tomography JCS GUIDELINES

Loss of pulp due to caries and pulpitis leads to loss of teeth and reduced quality of life. Thus, there is an unmet need for regeneration of pulp. A promising approach is stem cell therapy. Autologous pulp stem/progenitor (CD105(+)) cells were transplanted into a root canal with stromal cell-derived factor-1 (SDF-1) after pulpectomy in mature teeth with complete apical closure in dogs. The root canal was successfully filled with regenerated pulp including nerves and vasculature by day 14, followed by new dentin formation along the dentinal wall. The newly regenerated tissue was significantly larger in the transplantation of pulp CD105(+) cells with SDF-1 compared with those of adipose CD105(+) cells with SDF-1 or unfractionated total pulp cells with SDF-1. The pulp CD105(+) cells highly expressed angiogenic/neurotrophic factors compared with other cells and localized in the vicinity of newly formed capillaries after transplantation, demonstrating its potent trophic effects on neovascularization. Two-dimensional electrophoretic analyses and real-time reverse transcription-polymerase chain reaction analyses demonstrated that the qualitative and quantitative protein and mRNA expression patterns of the regenerated pulp were similar to those of normal pulp. Thus, this novel stem cell therapy is the first demonstration of complete pulp regeneration, implying novel treatment to preserve and save teeth.