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.     

Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis

Group B and C Neisseria meningitidis are the major cause of meningococcal disease in the United States and in Europe. N . meningitidis lipooligosaccharide (LOS), a major surface antigen, can be divided into 12 immunotypes of which L1 through L8 were found among Group B and C organisms. Groups B and C but not Group A may sialylate their LOSs with N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they synthesize CMP-NeuNAc. Using sialic acid-galactose binding lectins as probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4, L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis leukoagglutinin (MAL), which recognizes NeuNAcalpha2- 3Galbeta1-4GlcNAc/Glc sequence, but not to Sambucus nigra agglutinin, which binds NeuNAcalpha2-6Gal sequence. The combination of SDS-PAGE and MAL-blot analyses revealed that these six LOSs contained only the NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS components, which have a common terminal lacto-N-neotetraose (LNnT, Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown by previous studies. The LOS-lectin binding was abolished when the LOSs were treated with Newcastle disease viral neuraminidase which cleaves alpha2-->3 linked sialic acid. Methylation analysis of a representative LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide) and sialylparagloboside and some glycoproteins in having LNnT and N-acetyllactosamine sequences, respectively, with or without alpha2-->3 linked NeuNAc. The molecular mimicry of the LOSs may play a role in the pathogenesis of N.meningitidis by assisting the organism to evade host immune defenses in man.      

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.