Cholesterol modulates vascular reactivity to endothelin-1 by stimulating a pro-inflammatory pathway

Hypercholesterolemia (HC) is associated with coronary endothelial dysfunction and increased circulating levels of endothelin-1. We show that pre-treatment of intact rat aortic rings with cholesterol synergistically enhances the vasoconstriction induced by endothelin-1 suggesting that elevated levels of cholesterol may predispose to hypertension by modulating the vascular reactivity to endogenous vasoconstrictors. Moreover, we report that SB202190, a selective inhibitor of p38 MAPK, and PD98059 an inhibitor of MEK1/2 are able to abolish the vasoactive properties of cholesterol. MK-886, an inhibitor of 5-lipoxygenase is inefficient at blocking the vasoactive properties of cholesterol whereas NS-398, a selective inhibitor of cyclooxygenase-2 (COX-2) completely abolishes cholesterol-induced vasoconstriction. In intact rat aortae, cholesterol stimulates prostaglandin E(2) and prostaglandin F(2 alpha) production, an effect that can be completely prevented by inhibiting p38 MAPK, or COX-2. In vitro, cholesterol appears to stimulate a similar pro-inflammatory pathway in human cerebrovascular smooth muscle cells. Disruption of the MAPK/COX-2 pathway may represent a valuable therapy to block the hypertension associated with HC, as well as the development of atherosclerosis.     

Effects of heat-induced damage on the radial component of thermal diffusivity of bovine aorta

The extent of the change in thermal diffusivity of soft tissues due to heat-induced damage is not well known. Reported here are the results of using the flash method to measure the through-the-wall component of thermal diffusivity of bovine aorta before and after the tissue has undergone two hours of heating at 75 degrees C. The measurements indicate a 10.1 percent increase in the thermal diffusivity of the tissue post-heating. While this change may not result in a significant change in the tissue temperature profile, further study is needed to quantify the thermal diffusivity in other coordinate directions, as well as the mechanisms by which this change in properties occurs.     

A Description of Occurrence and Morphology of a New Species of Red-Water Forming Strombidium (Spirotrichea, Oligotrichia)

We describe a red-water ciliate, Strombidium lingulum n. sp., collected from a marine fjord in British Columbia (BC), Canada. In August, 1995, red-brown streaks were observed in the waters of Kyuquot Sound. BC. These streaks were composed of a ciliate population with an abundance in the surface of ˜ 1.5 × 10³ cells ml^-1. Density was reduced to < 50 cells ml^-1 below the surface. The bloom persisted for only a few hours; cells were observed for 3-4 days and were only occasionally observed in the weeks after the bloom. The red waters were speculated to be formed by a combination of downwelling events and an observed phototactic migration of the ciliate. As the ciliate was positively phototactic and pigmented, it may be mixotrophic; it was certainly heteroirophic, as it contained dinoflagellates and small ciliates in food vacuoles. Ciliates were preserved in Lugol's iodine and then both protargol stained and prepared for scanning electron microscopy.     

Heat-induced changes in the mechanics of a collagenous tissue: isothermal, isotonic shrinkage.

We present data from isothermal, isotonic-shrinkage tests wherein bovine chordae tendineae were subjected to well-defined constant temperatures (from 65 to 90 degrees C), durations of heating (from 180 to 3600 s), and isotonic uniaxial stresses during heating (from 100 to 650 kPa). Tissue response during heating and "recovery" at 37 degrees C following heating was evaluated in terms of the axial shrinkage, a gross indicator of underlying heat-induced denaturation. There were three key findings. First, scaling the heating time via temperature and load-dependent characteristic times for the denaturation process collapsed all shrinkage data to a single curve, and thereby revealed a time-temperature-load equivalency. Second, the characteristic times exhibited an Arrhenius-type behavior with temperature wherein the slopes were nearly independent of applied load--this suggested that applied loads during heating affect the activation entropy, not energy. Third, all specimens exhibited a time-dependent, partial recovery when returned to 37 degrees C following heating, but the degree of recovery decreased with increases in the load imposed during heating. These new findings on heat-induced changes in tissue behavior will aid in the design of improved clinical heating protocols and provide guidance for the requisite constitutive formulations.     

Not all free-living microorganisms have cosmopolitan distributions – the case of Nebela (Apodera) vas Certes (Protozoa: Amoebozoa: Arcellinida)

Aim  To review and critically assess the evidence that the testate amoeba species Nebela vas does not have a cosmopolitan distribution, in contradiction to the paradigm of microbial distribution that 'everything is everywhere'.
Location  Terrestrial and wetland habitats world-wide.
Methods  Relevant data were assembled on the morphology, ecology and global geographical distribution of N. vas from a comprehensive literature review of published original records. The data were collated, analysed and summarized. The roles of long-term and short-term agents of dispersal are discussed.
Results  A clear and repeated pattern has been elucidated of a microbial species, with a distinctive and unmistakeable morphology, that inhabits acid, damp terrestrial and wetland habitats in the southern cool-temperate and sub-Antarctic zones – including similar high-altitude habitats in the Tropics. It is almost entirely confined to the Gondwanaland continents and Southern Hemisphere islands. It is definitively absent from Holarctic regions. It is proposed that the continental distribution of N. vas is a consequence of continental drift following its original speciation in the Mesozoic or earlier, whereas its distribution on sub-Antarctic islands (glaciated in the Pleistocene) has been effected by dispersal from South America by wind around the Southern Ocean.
Main conclusion  Nebela vas is a proven instance of a microbial species that does not have a cosmopolitan distribution.     

Diverse functions of Hedgehog signaling in formation and physiology of steroidogenic organs

Adrenal, testis, and ovary are steroidogenic organs derived from a common primordium that consists of steroidogenic factor 1 (SF1)‐positive precursor cells. SF1 not only defines the steroidogenic lineages in these organs but also controls their differentiation. Recent evidence implicates the Hedgehog (Hh) signaling pathway as a downstream regulator of SF1 in the appearance of steroidogenic cells in these organs. The Hh signaling pathway serves as a common crosstalk component, yet has evolved diverse functions in the expansion and differentiation of the steroidogenic cells in a tissue‐specific manner. The purpose of this review is to compare and contrast the different roles of Hh signaling in these three organs during development. Mol. Reprod. Dev. 77: 489–496, 2010. © 2010 Wiley‐Liss, Inc.     

Bioactive compounds from Rumex plants

Two new naphthalene acylglucosides, rumexneposides A (1) and B (2), together with 12 known compounds (3-14), were isolated from the roots of Rumex nepalensis. Their structures were established by chemical and spectroscopic methods. The biological activities of compounds 1-14 as well as an additional 11 compounds previously isolated from R. nepalensis and Rumex hastatus (15–25) were evaluated against Mycobacterium tuberculosis, para-aminobenzoic acid (pAba) pathway, and a panel of human cancer cell lines. The results showed that compound 15 was the most active against M. tuberculosis with an MIC value of 2.85 μM similar to that of isoniazid. Compound 5 could inhibit pAba synthetic pathway with an MIC value of 12.6 μM, comparable to that of positive control abyssomicin C, representing a new example of the rare pAba pathway inhibitors.     

Heterogeneity in the Infection Biology of Campylobacter jejuni Isolates in Three Infection Models Reveals an Invasive and Virulent Phenotype in a ST21 Isolate from Poultry

Although Campylobacter is the leading cause of bacterial foodborne gastroenteritis in the world and the importance of poultry as a source of infection is well understood we know relatively little about its infection biology in the broiler chicken. Much of what we know about the biology of Campylobacter jejuni is based on infection of inbred or SPF laboratory lines of chickens with a small number of isolates used in most laboratory studies. Recently we have shown that both the host response and microbial ecology of C. jejuni in the broiler chicken varies with both the host-type and significantly between C. jejuni isolates. Here we describe heterogeneity in infection within a panel of C. jejuni isolates in two broiler chicken breeds, human intestinal epithelial cells and the Galleria insect model of virulence. All C. jejuni isolates colonised the chicken caeca, though colonisation of other parts of the gastrointestinal tract varied between isolates. Extra-intestinal spread to the liver varied between isolates and bird breed but a poultry isolate 13126 (sequence type 21) showed the greatest levels of extra-intestinal spread to the liver in both broiler breeds with over 70% of birds of the fast growing breed and 50% of the slower growing breed having C. jejuni in their livers. Crucially 13126 is significantly more invasive than other isolates in human intestinal epithelial cells and gave the highest mortality in the Galleria infection model. Taken together our findings suggest that not only is there considerable heterogeneity in the infection biology of C. jejuni in avian, mammalian and alternative models, but that some isolates have an invasive and virulent phenotype. Isolates with an invasive phenotype would pose a significant risk and increased difficulty in control in chicken production and coupled with the virulent phenotype seen in 13126 could be an increased risk to public health.     

PCR-Denaturing Gradient Gel Electrophoresis of Complex Microbial Communities: A Two-Step Approach to Address the Effect of Gel-to-Gel Variation and Allow Valid Comparisons Across a Large Dataset

Denaturing gradient gel electrophoresis (DGGE) is widely used in microbial ecology to profile complex microbial communities over time and in response to different stimuli. However, inherent gel-to-gel variability has always been a barrier toward meaningful interpretation of DGGE profiles obtained from multiple gels. To address this problem, we developed a two-step methodology to align DGGE profiles across a large dataset. The use of appropriate inter-gel standards was of vital importance since they provided the basis for efficient within- and between-gel alignment and a reliable means to evaluate the final outcome of the process. Pretreatment of DGGE profiles by a commercially available image analysis software package (TL120 v2006, Phoretix 1D Advanced) followed by a simple interpolation step in Matlab minimized the effect of gel-to-gel variation, allowing for comparisons between large numbers of samples with a high degree of confidence. At the same time, data were obtained in the form of whole densitometric curves, rather than as band presence/absence or intensity information, and could be readily analyzed by a collection of well-established multivariate methods. This work clearly demonstrates that there is still room for significant improvements as to the way large DGGE datasets are processed and statistically interrogated.