Quercetin-induced yeast apoptosis through mitochondrial dysfunction under the accumulation of magnesium in Candida albicans

Latterly, the upsurge in use of antifungal drugs has brought about the emergence of several drug-resistance strains, making it skeptical to continue relying on current therapeutic regime. In the necessity of resistance-free antifungal agent, flavonoids presented possibilities of replacing existing drugs, displaying antifungal activity against pathogenic fungi. Among them, quercetin, one of the most representative flavonoids, exhibited antifungal activity against Candida albicans. To inspect the further understanding regarding quercetin, the antifungal mode of action of quercetin was investigated. In the initial step, the apoptosis was monitored after quercetin treatment. Moreover, intracellular levels of Mg²⁺ was assessed and was determined that Mg²⁺ increase occurred under the influence of quercetin. In addition, several features of mitochondrial dysfunction were monitored. Mitochondrial dysfunction triggers decrease in mitochondrial redox levels and leads to disruption in mitochondrial antioxidant system. Increased intracellular ROS and decreased intracellular redox levels were also displayed, indicating the occurrence of overall disruption in antioxidant systems. Sequentially, DNA fragmentation was observed and this DNA damage in turn induces apoptosis. In analyses, hexaamminecobalt(III) chloride (Cohex) was applied to inhibit Mg²⁺ transport between cytosol and mitochondria. Cohex attenuated the effects induced by quercetin, which demonstrates that the presence of Mg²⁺ is essential in quercetin-induced apoptosis.     

A strategy for high cell density culture of heterotrophic microalgae with inhibitory substrates

Substrate inhibition is one of the major problems preventing high cell densities of microalgae in heterotrophic culture, so the possibility of overcoming the problem by various culture techniques was examined. It was found that perfusion culture may be the most appropriate technique for high cell densities in heterotrophic culture using inhibitory substrates. An experimental example in which a hollow fibre cell recycle system (HFCRS) was employed to achieve high cell densities of Chlamydomonas reinhardtii on acetate under heterotrophic conditions of growth was demonstrated. The cell density in the HFCRS was much higher than that reported in the literature for this species.     

The effect of somatostatins (SRIF-14, 25 and 28), galanin and anti-SRIF on plasma growth hormone levels in Coho salmon (Oncorhynchus kisutch, Walbaum)

Porcine galanin, somatostatins (SRIF-25 and SRIF-28) and invariant SRIF-14, known to have inhibitory-stimulatory actions on growth hormone (GH) secretion in higher vertebrates, were tested for their ability to affect plasma GH levels in coho salmon. Peptides were administered by intraperitoneal injection of 10 or 100 ng g⁻¹ body weight. All three SRIFs decreased plasma GH concentrations, their activity following the order SRIF-14 > SRIF-28 > SRIF-25. Galanin and an anti-SRIF produced pronounced, although transient increases in plasma GH.     

A gradient of synaptic efficacy and its presynaptic basis in the cercal system of the cockroach

1. The cerci of the cockroach Periplaneta americana bear longitudinal columns of wind-sensitive receptors which provide excitatory inputs to the giant interneurons (GIs) of the abdominal nerve cord. By using sound stimuli, we showed that spikes were more easily induced in the GIs from the most proximal than from the most distal receptors of the same column. 2. This was not due to a greater responsiveness of proximal sensilla to tones but to stronger synaptic connections; for the 3 largest GIs, the amplitude of the monosynaptic unitary EPSP tended to be all the higher as the stimulated sensillum was more proximal in each column. 3. The differences in EPSP size were due, at least partly, to presynaptic factors: a statistical analysis of the amplitude fluctuations of single-fibre EPSPs, showed that the amount of transmitter released per presynaptic impulse was larger for proximal than for distal sensory neurons in each column. 4. These differences in synaptic strength were correlated with differences in the structure of the afferent terminals. The location, the size and the shape of the axonal arbors are nearly the same for all sensory neurons of the same column, but proximal neurons arborize more profusely, and the terminal arbor of distal neurons is generally characterized by dorsal clusters of varicosities. 5. During postembryonic development, a decrease in the connection strength of 2 identified cercal neurons was accompanied by a retraction of ramifications on the medial side of their axonal arbor. 6. Possible mechanisms involved in the genesis and the remodelling of the gradient of synaptic strength are discussed in the light of available data and hypotheses relative to the development of ordered afferent connections.     

Adenylyl cyclase in yeast: antibodies and mutations identify a regulatory domain

The adenylyl cyclase system of the yeast Saccharomyces cerevisiae contains the CYR1 polypeptide, responsible for catalyzing formation of cAMP from ATP, and two RAS polypeptides, responsible for stimulation of cAMP synthesis by guanine nucleotides. We have obtained rabbit antibodies that recognize the CYR1 protein. Antibodies were raised against synthetic oligopeptides and against a recombinant beta-galactosidase/CYR1 fusion protein. These antibodies have allowed the identification of the CYR1 gene product as a 205 kDa protein. Treatment with trypsin (2 micrograms/ml) reduced the size of the CYR1 protein from 205 to 155 kDa and produced an activated enzyme which no longer responded to guanine nucleotides. This result is consistent with a model in which adenylyl cyclase activity is regulated by an inhibitory domain near the amino-terminus of the CYR1 protein. This model is further supported by the finding that adenylyl cyclase activity is also markedly elevated and unresponsive to guanine nucleotides in mutant yeast strains that express only the carboxy-terminal half of the CYR1 protein. Treatment with high trypsin concentrations (greater than 10 micrograms/ml) caused release of adenylyl cyclase activity from the membrane. Comparison of immunoreactive CYR1 fragments released by trypsin and membrane bound genetically altered proteins suggests that the CYR1 protein is attached to the membrane via a separate trypsin sensitive anchoring protein rather than via a membrane anchoring domain.     

Anatomy of antenno-cerebral pathways in the brain of the sphinx moth Manduca sexta

Summary In the moth Manduca sexta, the number and morphology of neuronal connections between the antennal lobes and the protocerebrum were examined. Cobalt injections revealed eight morphological types of neurons with somata adjacent to the AL neuropil that project in the inner, middle, and outer antenno-cerebral tracts to the protocerebrum. Neurons innervating the macroglomerular complex and many neurons with fibers in the inner antennocerebral tract have uniglomerular antennal-lobe arborizations. Most neurons in the middle and outer antenno-cerebral tracts, on the other hand, seem to innervate more than one glomerulus. Protocerebral areas receiving direct input from the antennal lobe include the calyces of the mushroom bodies, and circumscribed areas termed olfactory foci in the lateral horn of the protocerebrum and several other regions, especially areas in close proximity to the mushroom bodies. Fibers in the inner antenno-cerebral tract that innervate the male-specific macroglomerular complex have arborizations in the protocerebrum that are distinct from the projections of sexually non-specific neurons. Protocerebral neurons projecting into the antennal lobe are much less numerous than antennal-lobe output cells. Most of these protocerebral fibers enter the antennal lobe in small fiber tracts that are different from those described above. In the protocerebrum, these centrifugal cells arborize in olfactory foci and also in the inferior median protocerebrum and the lateral accessory lobes. The morphological diversity of connections between the antennal lobes and the protocerebrum, described here for the first time on a single-cell level, suggests a much greater physiological complexity of the olfactory system than has been assumed so far.     

Anoxic block of GABAergic IPSPs

In rat hippocampal slices GABAergic IPSPs are very rapidly suppressed by anoxia (in<2 min). Both early (GABA_A) and late (GABA_B) components are affected. After reoxygenation, the IPSPs recover, but only slowly and not always completely. Iontophoretic applications of GABA or baclofen indicated no major depression of responses during anoxia. It is therefore unlikely that the anoxic suppression of IPSPs is caused by desensitizations of GABA receptors. A more probable explanation is a failure of GABAergic neurons to release GABA from inhibitory nerve terminals.Special issue dedicated to Dr. Eugene Roberts.     

担子菌多糖及羊脾RNA对肿瘤的抑制与有关组织中cAMP含量关系的探讨

本文讨论了对带瘤小鼠注射香菇多糖、松口蘑多糖和羊脾RNA后,活体内有关组织中cAMP含量与抑瘤率之间的关系。 结果表明,上述活性物质不仅增强了机体免疫活性,同时亦促使机体内脾、瘤等组织的cAMP增高,此种增高,与抑瘤率成正相关。     

Effects of secretin and gastric inhibitory polypeptide on human pancreatic growth hormone-releasing factor(1-40)-stimulated growth hormone levels in the rat

Synthetic human pancreatic growth hormone-releasing factor containing 40 amino acids ([hpGRF (1-40)]-OH) significantly stimulated plasma growth hormone (GH) levels in both sodium pentobarbital and urethane anesthetized rats. Synthetic secretin, gastric inhibitory polypeptide (GIP), and glucagon significantly decreased plasma GH levels while synthetic vasoactive intestinal peptide (VIP) had no effect. Secretin and GIP also altered the in vivo plasma GH response to [hpGRF(1-40)]-OH. Whether this effect is the result of an interaction at the pituitary level or is due to an extra-pituitary effect of secretin and GIP awaits further study.     

Dose-response comparisons of canine plasma gastroenteropancreatic hormone responses to bombesin and the porcine gastrin-releasing peptide (GRP)

This study compares the potencies of the porcine gastrin-releasing peptide (pGRP) and bombesin, in causing elevations of canine plasma gastroenteropancreatic (GEP) levels. In the dose range 0-600 pmol . kg-1 . h-1, infusion of both peptides resulted in obvious dose-related elevations of plasma levels of gastrin, pancreatic polypeptide, enteroglucagon, immunoreactive pancreatic glucagon, and insulin. In this dose range, no significant difference in potency between the two peptides in elevating plasma levels of the above hormones was observed. The results of this study, demonstrating equimolar potency of pGRP and bombesin, are in contrast to previous studies reporting that pGRP was less potent than bombesin in causing certain bioactivities in the rat following intracranial administration of the two peptides.