The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence

The blood-brain barrier (BBB) is composed of tightly bound endothelial cells (ECs) and perivascular astrocytes that regulate central nervous system (CNS) homeostasis. We showed that astrocytes secrete Sonic hedgehog and that BBB ECs express Hedgehog (Hh) receptors, which together promote BBB formation and integrity during embryonic development and adulthood. Using pharmacological inhibition and genetic inactivation of the Hh signaling pathway in ECs, we also demonstrated a critical role of the Hh pathway in promoting the immune quiescence of BBB ECs by decreasing the expression of proinflammatory mediators and the adhesion and migration of leukocytes, in vivo and in vitro. Overall, the Hh pathway provides a barrier-promoting effect and an endogenous anti-inflammatory balance to CNS-directed immune attacks, as occurs in multiple sclerosis.     

TRPM4 regulates calcium oscillations after T cell activation

TRPM4 has recently been described as a calcium-activated nonselective (CAN) cation channel that mediates membrane depolarization. However, the functional importance of TRPM4 in the context of calcium (Ca2+) signaling and its effect on cellular responses are not known. Here, the molecular inhibition of endogenous TRPM4 in T cells was shown to suppress TRPM4 currents, with a profound influence on receptor-mediated Ca2+ mobilization. Agonist-mediated oscillations in intracellular Ca2+ concentration ([Ca2+]i), which are driven by store-operated Ca2+ influx, were transformed into a sustained elevation in [Ca2+]i. This increase in Ca2+ influx enhanced interleukin-2 production. Thus, TRPM4-mediated depolarization modulates Ca2+ oscillations, with downstream effects on cytokine production in T lymphocytes.     

Purification of a Low Molecular Weight Fucoidan for SPECT Molecular Imaging of Myocardial Infarction

Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led to a purified fraction with a yield of 45%. The physicochemical characterizations of the purified fucoidan using colorimetric assay, MALLS, dRI, FT-IR, NMR, exhibited molecular weight distributions and chemical profiles similar for both fucoidans whereas the sulfate and l-fucose contents increased by 16% and 71%, respectively. The biodistribution study in rat of both compounds labeled with ^99mTc evidenced a predominant renal elimination of the purified fucoidan, but the crude fucoidan was mainly retained in liver and spleen. In rat myocardial ischemia-reperfusion, we then demonstrated the better efficiency of the purified fucoidan. This purified sulfated polysaccharide appears promising for the development of molecular imaging in acute coronary syndrome.     

A miniaturized method for fast,simple, and sensitive pesticide analysis in soils

Journal of Soils and Sediments - Organochlorine pesticides (OCPs) like lindane and DDT have been used extensively after World War II until the 1990s. Still, residues of these pesticides can be...     

Investigating Wild Berries as a Dietary Approach to Reducing the Formation of Advanced Glycation Endproducts: Chemical Correlates of In Vitro Antiglycation Activity

Evidence supports the health promoting benefits of berries, particularly with regard to the prevention and management of chronic diseases such cardio- and cerebrovascular disease, diabetes and Alzheimer’s disease. Two related pathophysiological features common to many of these conditions are oxidative stress and the accumulation of advanced glycation endproducts (AGEs). Whereas antioxidant properties are well-established in several species of berries and are believed central to their protective mechanisms, few studies have investigated the effects of berries on AGE formation. Here, employing a series of complementary in vitro assays, we evaluated a collection of wild berry extracts for 1) inhibitory effects on fluorescent-AGE and Nε- (carboxymethyl)lysine-albumin adduct formation, 2) radical scavenging activity and 3) total phenolic and anthocyanin content. All samples reduced AGE formation in a concentration-dependent manner that correlated positively with each extract’s total phenolic content and, to a lesser degree, total anthocyanin content. Inhibition of AGE formation was similarly related to radical scavenging activities. Adding antiglycation activity to the list of established functional properties ascribed to berries and their phenolic metabolites, our data provide further insight into the active compounds and protective mechanisms through which berry consumption may aid in the prevention and treatment of chronic diseases associated with AGE accumulation and toxicity. As widely available, safe and nutritious foods, berries represent a promising dietary intervention worthy of further investigation.     

trans-C18:1 isomers in cheeses enriched in unsaturated fatty acids and manufactured with different milk fat globule sizes

Increasing the knowledge on dietary fat composition, mainly the minor components, will improve the nutritional value of foods and their labeling. In this study, we examined the trans-octadecenoic acid (C18:1) composition of Emmental cheeses enriched in unsaturated fatty acids (FA) and manufactured with milks produced by cows selected to produce small and large fat globules. The FA composition of the milks was not significantly ( P > 0.05) different from the FA composition of the corresponding Emmental cheeses. Increasing the unsaturated FA content of the cheeses using dietary manipulations lead to an increase in the trans-C18:1 and changed their isomeric profiles. In milk fat produced with the linseed-enriched diet, the trans-10 C18:1 concentration was greater than trans-11 C18:1 (vaccenic acid), which is classically the major trans-C18:1 in milk fat. The content in trans-C18:1 and more particularly in trans-10 C18:1 was negatively correlated with the size of fat globules ( r (2) = 0. 82 and 0.87, respectively) and related to milk fat depression. The trans-C18:1 content was negatively correlated with the saturated FA (slope = -0.35; r (2) = 0.81) and positively correlated with the unsaturated (slope = 0.29; r (2) = 0.85) and monounsaturated (slope = 0.32; r (2) = 0.81) FA. Focusing on the health-related considerations of fat in food products, further nutritional studies are needed to elucidate the role of trans-C18:1 isomers.     

Characterization of metabolites of fungicidal cymoxanil in a sensitive strain of Botrytis cinerea

The metabolism of cymoxanil [1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea] by a very sensitive strain of Botrytis cinerea toward this fungicide was studied by using [2-(14)C]-cymoxanil. Labeled cymoxanil was added either in a culture of this strain or in its enzymatic extract. The main metabolites, detected in biological samples, were isolated and identified by mass and NMR spectrometry. Their identification allowed us to show that this strain quickly metabolized cymoxanil according to at least three enzymatic pathways: (i) cyclization leading, after hydrolysis, to ethyl parabanic acid, (ii) reduction giving demethoxylated cymoxanil, and (iii) hydrolysis and reduction followed by acetylation leading to N-acetylcyanoglycine. In a cell-free extract of the same strain, only the first and the second enzymatic reactions, quoted above, occurred. Biological tests showed that, among all the metabolites, only N-acetylcyanoglycine is fungitoxic toward this sensitive strain.     

Phenolic compounds contribute to dark bran pigmentation in hard white wheat

Unacceptably dark bran color has prevented the white-kernelled variety Argent from meeting grain color marketing standards for hard white wheats (Triticum aestivum L.). The objective of this research was to identify phenolic compounds that negatively affect bran color in white wheat using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and vanillin-HCl and NaOH staining methods. In mature bran, FT-ICR-MS detected derivatives of the flavonol quercetin in varieties Argent and RL4137 (red-kernelled wheat) but not in W98616, a white wheat variety with acceptable grain color. Derivatives of the isoflavone formononetin were more abundant in W98616 relative to RL4137 and Argent. Vanillin-HCl staining indicated that RL4137 sequestered high levels of proanthocyanidin (PA) throughout its entire seed coat, whereas white wheats sequestered PAs as discrete speckles. Argent possessed abundant speckles over its entire seed coat, whereas speckles were almost undetectable in W98616. In mature kernels, flavonoids throughout the seed coat of RL4137 reacted with NaOH, but only the speckles appeared to react in white wheats. W98616 consistently had lighter grain than Argent before and after NaOH treatment. Free and bound phenolic differences in bran samples confirmed that the darker seed coat color of Argent, relative to W98616, was likely due to higher total phenolic acid content. Although isoflavones accumulated in Argent and RL4137, it appears that the majority of the flux through the flavonoid pathway ultimately accumulates quercetin derivatives and PAs. In W98616, PAs accumulate, but it appears that flavonoid biosynthesis ultimately accumulates isoflavones. Argent, compared to W98616, generally accumulated higher levels of total phenolics (flavonols, stilbenes, and PAs) within its darker pigmented bran.     

Irradiance-induced plasticity in the hydraulic properties of saplings of different temperate broad-leaved forest tree species

We assessed the irradiance-related plasticity of hydraulic architecture in saplings of Betula pendula Roth., a pioneer species; Acer pseudoplatanus L., Fraxinus excelsior L. and Quercus robur L., which are post-pioneer light-requiring species; and Quercus petraea Matt. Liebl. and Fagus sylvatica L. Plants were grown in pots in 36%, 16% and 4% of full sunlight. Hydraulic conductance was measured with a high-pressure flow-meter in entire, in situ root systems and in excised shoots. Leaf-specific whole-plant conductance (LSC) increased with irradiance, due, in part, to an effect of irradiance on plant size. In addition, there was a size-independent effect of irradiance on LSC due, in part, to an increase in root hydraulic conductance paralleled by an increase in root biomass scaled to leaf area. Changes in shoot conductivity also contributed to the size-independent plasticity of LSC. Vulnerability to cavitation measured in current-year twigs was much larger in shade-grown plants. Betula pendula had the highest whole-plant, root and shoot conductances and also the greatest vulnerability to cavitation. The other species were similar in LSC, but showed some variation in root conductance scaled to biomass, with Q. robur, Q. petraea and F. sylvatica having the lowest root conductance and susceptibility to cavitation. All species showed a similar irradiance-related plasticity in LSC.     

Induction of hypericins in Hypericum perforatum in response to chromium

Seedlings of Hypericum perforatum were grown with 0.01 and 0.1 mM of chromium added to the nutrient media. A treatment with 0.01 mM Cr(VI) for seven days resulted in an increased production of protopseudohypericin (+135%), hypericin (+38%) and pseudohypericin (+5%). Treatment with 0.1 mM Cr(VI) for two days also caused an increase of protopseudohypericin (+167%), hypericin (25%) and pseudohypericin (+5%). The greatest effect of chromium treatment was observed at a concentration of 0.1 mM for seven days: protopseudohypericin increased +404% and pseudohypericin to +379%. Hypericin was not affected by this treatment.