Selective effects of PHA on rat brush border hydrolases along the crypt-villus axis

The mechanism of the toxicity of lectin from Phaseolus vulgaris seeds has been investigated on rat enterocytes. Cell isolation procedures showed a selectivity in the loss of brush border hydrolases; this indicated that the microvilli blebbing was not the only mechanism of action of lectins on rat enterocytes.     

Complement evasion by the Lyme disease spirocheteBorrelia burgdorferi grown in host-derived tissue co-cultures: role of fibronectin in complement-resistance

The effectiveness of complement-mediated killing ofBorrelia burgdorferi, the causative agent of Lyme disease, in the presence of host-derived tissues was studied. Second and high passage forms ofB. burgdorferi 297 isolate were grown in a LEW/N rat joint tissue co-culture system and in artificial BSK medium. Guinea pig complement and third week immune serum from hamsters with experimental Lyme disease were added to the cultures. Both high and low passage borrelia grown in BSK medium died and did not revive after 3 weeks incubation in BSK medium. However, 5–12% of tissue co-cultured borrelia survived the first complement-mediated lysis. Repeated re-growth and lysis cycles in tissue co-culture resulted in isolation of an 85% complement-resistant population ofB. burgdorferi. Joint tissue culture supernatant collected on the third day of tissue culture, and fibronectin (25 g/ml), also protected spirochetes from complement-mediated lysis in contrast to BSK or fresh co-culture medium. Complement-mediated lysis may not be an effective mechanism in eradication of borrelia, and the chronicity of Lyme disease may be due to resistance ofB. burgdorferi variants to host immune defense mechanisms in the presence of host-derived tissues.     

Novel diterpenoid diacylglycerols from marine molluscs: potent morphogens and protein kinase C activators

Five novel 1,2-sn-diacylglycerols with diterpenoid acyl moieties in thesn-1 position were isolated and characterized, together with the corresponding 1,3-sn-diacylglycerols, from three species of dorid nudibranchs molluscs. Their potent activity as morphogens in vivo in theHydra tentacle regeneration assay and their parallel activity as activators of rat brain protein kinase C (PKC) in vitro are reported here. Our findings promote the use of these compounds as useful molecular probes for both in vivo and in vitro studies on the participation of PKC in cell development.     

Effect of dexamethasone on Fc gamma receptor expression in foetal and neonatal rat gut

When injected into 12-day-old suckling rats, dexamethasone caused a precocious disappearance of Fc gamma receptors from enterocytes of the proximal small intestine. However, dexamethasone appeared to be necessary for the maintenance or production of such receptors in foetal rat gut cultured in vitro.     

Effect of steviol and its structural analogues on glucose production and oxygen uptake in rat renal tubules

Summary The effect of several natural products ofStevia rebaudiana on glucose production and oxygen uptake in rat renal cortical tubules was investigated. Steviol, isosteviol and glucosilsteviol decreased glucose production and inhibited oxygen uptake. The sweet principle stevioside, and steviolbioside, however, were without effect on gluconeogenesis and oxygen uptake.     

What leads from <Emphasis Type="Italic">dead-end?</Emphasis>

The 129 mouse strain develops congenital testicular germ cell tumors (TGCTs) at a low frequency. TGCTs in mice resemble the testicular tumors (teratomas) that occur in human infants. The genes that cause these tumors in 129 have not been identified. The defect at the Ter locus increases TGCT incidence such that 94% of 129-Ter/Ter males develop TGCTs. The primary effect of the Ter mutation is progressive loss of primordial germ cells (PGCs) during embryonic development. This results in sterility in adult Ter/Ter mice on all mouse strain backgrounds. However, on the 129 background, Ter causes tumor development in addition to sterility. Therefore, Ter acts as a modifier of 129-derived TGCT susceptibility genes. Ter was identified to be a mutation that inactivates the Dead-end1 (Dnd1) gene. In this perspective, I discuss the possible areas of future investigations to elucidate the mechanism of TGCT development due to Dnd1 inactivation. Received 29 September 2006; received after revision 29 January 2007; accepted 19 February 2007     

Effect of dexamethasone on Fc γ receptor expression in foetal and neonatal rat gut

Summary When injected into 12-day-old suckling rats, dexamethasone caused a precocious disappearance of Fc receptors from enterocytes of the proximal small intestine. However, dexamethasone appeared to be necessary for the maintenance or production of such receptors in foetal rat gut cultured in vitro.Supported by an award from the Science and Engineering Research Council.     

A possible metabolic role foro-diphenoloxidase inMycobacterium leprae

Summary Among mycobacteria,Mycobacterium leprae is unique in its ability to oxidize a variety of diphenols to quinones in vitro. What physiologic roleo-diphenoloxidase has in the organism remained unknown. Reducing substrates like NADPH, NADH and ascorbic acid reacted with the quinone formed from dopa (3,4-dihydroxyphenylalanine); the substrates were oxidized and the quinone was reduced back to diphenol in the process. Since the quinone undergoes reversible oxidation-reduction, diphenoloxidase might serve as an alternative respiratory mechanism inM. leprae for the utilization of other substrates, as has been reported in plants.     

Induction of autotomy in the American bird grasshopperSchistocerca americana (Drury) by the ecdysone agonist RH-5849 and investigation of its mode of action

The non-steroidal ecdysone agonist RH-5849 (1,2-dibenzoyl-l-tert-butylhydrazine) was found to be an effective neurotoxicant on injection into the American bird grasshopper,Schistocerca americana (Drury). Treated grasshoppers became immediately hyperactive, followed by loss of coordination, paralysis and eventually death. We also discovered that this compound induced bilateral autotomy of the metathoracic legs during the early stages of intoxication. However, no evidence of ecdysonergic or morphogenetic activities was observed. Synergism studies with neurotoxins of known mode of action suggested that RH-5849 has a mechanism of action similar to that of 4-amino pyridine, which blocks potassium channels.     

Biosynthesis of 1-alkenes in the defensive secretions ofTribolium confusum (Tenebrionidae); stereochemical implications

Summary The terminally unsaturated hydrocarbons of the defensive secretion ofTribolium confusum are biosynthesized from fatty acids by oxidative decarboxylation. The process involves an enantiospecific cleavage of the C–H bond of thepro-(S) C(3)–H atom and simultaneous decarboxylation of the acid into an 1-alkene and carbon dioxide via ananti-periplanar transition state geometry (anti-elimination). The stereochemistry of this biotranformation is identical in all respects with the same reaction in higher plants. The mechanism seems to be of general importance for the biosynthesis of many vinylic substructures of natural products from oxygen-containing precursors.     

Antifungal properties of taxol and various analogues

The antimitotic agent taxol was tested for toxicity towards fungi from different taxonomic groups and found to be particularly active against oomycete fungi. In germinating zoospore cysts of the oomycetePhytophthora capsici the mechanism of action of taxol was shown to involve inhibition of mitosis, presumably resulting from an effect on microtubules. Various taxol analogues with deleted A-ring C-13 side chain substituents were tested for toxicity towardsP. capsici andAphanomyces cochlioides to provide insight into structural features required for activity. The importance of the side chain was shown by the much lower activity as compared to taxol of analogues lacking all or part of the side chain. The effect of stereochemistry at the C-2 position on fungitoxicity towards oomycetes was similar to that reported previously on mammalian microtubule assembly.     

Intestinal vasoactive peptide receptors in enterocytes : specific binding and stimulation of cyclic AMP]

Receptors for the vasoactive intestinal peptide (VIP) were characterized on enterocytes isolated from Rat small intestine. Native VIP inhibited competitively the binding of 125I-VIP to enterocytes and strongly stimulated cyclic AMP production; both these effects were observed for concentrations of VIP as low as 0.5-1.0 ng/ml (0.15-0.30 nM) which are compatible with the VIP concentration in the gut.     

Effect of phosphonic analogues of glutamic acid on glutamate decarboxylase

Summary Among the phosphonic analogues of glutamic acid, only 4-amino-4-phosphono butyric acid, the compound which shows the highest affinity for pyridoxal phosphate, inhibits competitively bothEscherichia coli and rat brain glutamate decarboxylases. Phosphinothricin, 2-amino-4-(methylphosphino)butyric acid, is a strong inhibitor of the mammalian enzyme.We acknowledge the gift of a sample of phosphinothricin by Prof. Przemyslaw Mastalerz as well as the technical assistance of Denois.     

Hemokinins and endokinins

The mammalian tachykinins are a family of peptides that, until recently, has included substance P (SP), neurokinin A and neurokinin B. Since, the discovery of a third preprotachykinin gene (TAC4), the number of tachykinins has more than doubled to reveal several species-divergent peptides. This group includes hemokinin-1 (HK-1) in mouse and rat, endokinin-1 (EK-1) in rabbit, and EKA, EKB, human HK-1 (hHK-1) and hHK(4–11) in humans. Each exhibits a remarkable selectivity and potency for the tachykinin NK₁ receptor similar to SP. Their peripheral expression has led to the proposal that they are the endogenous peripheral SP-like endocrine/paracrine agonists where SP is not expressed. Moreover, their strong cross-reactivity with a specific SP antibody leads us to question many of the proposed locations and roles of SP in the periphery. Additionally, three orphan tachykinin gene-related peptides are identified on TAC4, in rabbit, EK-2 and in humans, EKC and EKD.Received 25 January 2004; received after revision 18 February 2004; accepted 27 February 2004     

Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion

Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Src binds to EGFR and is required for localization of EGFR and Dsg2 to cell–cell contacts. EGFR is critical for cell adhesion and barrier recovery. In line with this, Dsg2-deficient enterocytes display impaired barrier properties and increased cell proliferation. Mechanistically, Dsg2 directly interacts with EGFR and undergoes heterotypic-binding events on the surface of living enterocytes via its extracellular domain as revealed by atomic force microscopy. Thus, our study reveals a new mechanism by which Dsg2 via Src shapes EGFR function towards cell adhesion.     

6H-anthra[1,9-bc]thiophene derivatives from a bryozoan,Dakaira subovoidea

Separation of a lipophilic extract of the bryozoan,Dakaira subovoidea, a common fouling organism of underwater structures, guided by inhibition of lipid peroxide formation in rat liver microsomes, gave 5,7-dihydroxy-1-hydroxymethyl-6-oxo-6H-anthra[1,9-bc]thiophene (1a) and its 1-methoxycarbonyl derivative (1c), together with the known 1,8-dihydroxyanthraquinone (2). The structures were determined by spectral and crystallographic analyses.     

Possible involvement of the phloem sealing system in the acceptance of a plant as host by an aphid

Possible reasons for the rejection of some lines ofTriticum monococcum (Tm44 and Tm46) by the aphidSitobion avenae were explored. In allT. monococcum lines studied, whether unfavourable (non-host/resistant plant) or favourable (host/susceptible plant), the concentrations of hydroxamic acids, a family of aphid-resistance factors in cereals, were significantly lower than the levels in the favourable host-plantTriticum aestivum cv. Therefore, hydroxamic acids did not account for the host/non-host patterns observed. Phloem sap was collected by stylectomy from young seedlings of favourable and unfavourable plants. In non-aphid-resistant genotypes, the success in stylectomy, the proportion of amputated stylets resulting in long (>1 min) exudations, the average duration of exudation, and the final volume of sap exuded, were higher than in the aphid-resistant genotypes. It is concluded that aphid interference with the phloem sealing system of the plant is a likely mechanism of rejection ofT. monococcum lines Tm44 and Tm46 as hosts byS. avenae.     

Circadian rhythmicity is involved in photoperiodic time measurement in the aphidMegoura viciae

The photoperiodic clock in the vetch aphidMegoura viciae is generally accepted to be based on a non-circadian mechanism or hourglass, as no evidence has been found for the involvement of the circadian system in the photoperiodic response. By using a recently-devised protocol which discriminates between single and repeated night length measurement, we demonstrate here that long-night measurement inMegoura is executed in a repetitive way, and thus that its photoperiodic clock is based on a circadian oscillator after all. However, it is also apparent that the determination of short nights is not repetitive.Dedicated to our dear friend, the late Professor A. D. (tony) Lees who, sadly, died before we had a chance to discuss the data reported here.     

Powerful hepatoprotective and hepatotoxic plant oligostilbenes,isolated from the Oriental medicinal plantVitis coignetiae (Vitaceae)

The methanol extract of the Oriental medicinal plantVitis coignetiae (Vitaceae) showed hepatoprotective activity in the in vitro assay method using primary cultured rat hepatocytes. Activity-guided fractionation of the extract afforded -viniferin as an active principle. The protective effect of -viniferin against mice carbon tetrachloride-induced hepatic injury in mice was shown by serum enzyme assay as well as by pathological examination. In addition to -viniferin, plant oligostilbenes, ampelopsins A, C, F and the mixture of vitisin A andcis-vitisin A were also present in the extract. Among them, ampelopsin C and the mixture of vitisin A andcis-vitisin A were found to be powerful hepatotoxins.