BMP receptor-integrin interaction mediates responses of vascular endothelial Smad1/5 and proliferation to disturbed flow.

BACKGROUND: Vascular endothelial cells (ECs) are constantly exposed to blood flow-induced shear stress. Our previous study demonstrated that disturbed flow with low and oscillatory shear stress (OSS) induces bone morphogenetic protein receptor (BMPR)-specific Smad1/5 activation in ECs, but the underlying mechanisms and the in vivo functional role of Smad1/5 remain unclear. OBJECTIVES: Here we elucidated the molecular mechanisms by which OSS activates EC Smad1/5 and its in vivo functional role. METHODS: Lentiviral Smad5-specific short hairpin RNA (Lenti-shSmad5) was constructed and intra-arterially injected into the lumen of stenosed abdominal aorta in bromodeoxyuridine-infused rats. Co-immunoprecipitation and in situ proximity ligation assays were performed on ECs exposed to OSS (0.5 ± 4 dynes/cm(2) ) in a parallel-plate flow chamber to investigate BMPR-integrin interactions and their regulatory role in OSS-activation of EC Smad1/5. RESULTS: Intra-arterial administration of Lenti-shSmad5 inhibited bromodeoxyuridine uptake of ECs at post-stenotic sites, where disturbed flow with OSS occurs. OSS induced sustained BMPRIB-αv ß3 integrin association in ECs, which was mediated by the intracytoplasmic kinase domain of BMPRII and subsequently activated the Shc/focal adhesion kinase (FAK)/extracellular signal-regulated kinase (ERK) cascade, leading to Smad1/5 activation. This OSS-activation of Smad1/5 induced its association with and activation of runt-related transcription factor-2 (Runx2), leading to activations of mammalian target of rapamycin (mTOR) and p70S6 kinase (p70S6K), a pathway critical for EC proliferation in response to OSS. CONCLUSIONS: Oscillatory shear stress induces synergistic interactions between specific BMPRs and integrin to activate Smad1/5 through the Shc/FAK/ERK pathway, which leads to the activation of the Runx2/mTOR/p70S6K pathway to promote EC proliferation.

Detection of Rickettsia spp. and host and habitat associations of fleas (Siphonaptera) in eastern Taiwan.

Rickettsia typhi and Rickettsia felis (Rickettsiales: Rickettsiaceae) are two rickettsiae principally transmitted by fleas, but the detection of either pathogen has rarely been attempted in Taiwan. Of 2048 small mammals trapped in eastern Taiwan, Apodemus agrarius Pallas (24.5%) and Mus caroli Bonhote (24.4%) (both: Rodentia: Muridae) were the most abundant, and M. caroli hosted the highest proportion of fleas (63.9% of 330 fleas). Two flea species were identified: Stivalius aporus Jordan and Rothschild (Siphonaptera: Stivaliidae), and Acropsylla episema Rothschild (Siphonaptera: Leptopsyllidae). Nested polymerase chain reaction targeting parts of the ompB and gltA genes showed six fleas to be positive for Rickettsia spp. (3.8% of 160 samples), which showed the greatest similarity to R. felis, Rickettsia japonica, Rickettsia conorii or Rickettsia sp. TwKM01. Rickettsia typhi was not detected in the fleas and Rickettsia co-infection did not occur. Both flea species were more abundant during months with lower temperatures and less rainfall, and flea abundance on M. caroli was not related to soil hardness, vegetative height, ground cover by litter or by understory layer, or the abundance of M. caroli. Our study reveals the potential circulation of R. felis and other rickettsiae in eastern Taiwan, necessitating further surveillance of rickettsial diseases in this region. This is especially important because many novel rickettsioses are emerging worldwide.

Differential role of the hippocampus in response-outcome and context-outcome learning: evidence from selective satiation procedures.

Instrumental performance in rats with hippocampal lesions is insensitive to the degradation of action-outcome contingencies, but sensitive to the effects of selective devaluation by satiation. One interpretation of this dissociation is that damage to the hippocampus impairs the formation of context-outcome associations upon which the effect of contingency degradation, but not selective satiation, relies. Here, we provide a direct assessment of this interpretation, and showed that conditioned responding to contexts did not show sensitivity to selective satiation (Experiment 1), and confirmed that instrumental performance was sensitive to selective satiation (Experiment 2) following hippocampal cell loss.

Annual variation in semen characteristics of pigeons (Columba livia).

The purpose of this study was to evaluate annual semen characteristics of pigeons (Columba livia). Ten selected male pigeons, aged 2 to 5 yr were housed under natural environmental conditions, and semen collection was conducted via a digital massage twice weekly throughout the year. The success rate of semen collection in a total of 920 attempts was 40% (371/920) over the whole year. The highest success rate was 69% (55/80) in March followed by 66% (53/80) in November, whereas the lowest rates were in August (13%,10/80) and September (13%, 8/60) (P < 0.01). Volume of the ejaculate averaged 11.0 +/- 0.9 microL (mean +/- SEM). The greatest volume was obtained in November (13.5 +/- 1.0 microL), whereas the least was obtained in August (7.0 +/- 1.0 microL). The average sperm motility was 72 +/- 2% of all ejaculates, of which the highest motility (82 +/- 2%) was observed in March, whereas the least motility (48 +/- 3%) was in August. Sperm viability and sperm motility were positively correlated (r = 0.91; P < 0.01). Maximum sperm concentration was 4.9 +/- 0.4 x 10(9) sperm/mL noted in March, whereas the minimum was 3.8 +/- 0.2 x 10(9) sperm/mL observed in October. Donors generally exhibited susceptible (54%) or dull submission (43%), whereas resistance to handling was rarely observed (3%). During collections, a red (47%) or pink (44%) cloacal membrane was often observed, whereas during only 9% of the collections, the cloacal membrane was pale. When the ambient temperature decreased below 15 C, semen could not be obtained (0/80). A high amount of semen (>10 microL) was obtained when the temperature ranged between 19 and 24 C. Optimal sperm motility (approximately 80%) and viability (>85%) was observed when the temperature was between 18 and 24 C. At temperatures greater than 28 C, sperm motility and viability decreased. Sperm concentration was not significantly influenced by temperature fluctuations. In summary, annual variation in semen characteristics exhibited two peaks per year with mean motility and viability reaching peak annual values in March and November. Both of these months had mean ambient temperatures between 19 and 24 C, a range associated with maximal ejaculatory volumes.