海洋浮游藻类细胞质膜氧化还原活性与细胞外CA活性的关系

海洋浮游藻类除通过吸收和释放分子与离子来改变其环境的化学成分外,还可通过细胞外表面一些酶的作用引起质膜外化学物质变化。在这方面,海洋浮游藻类一个主要的细胞外表面酶-碳酸酐酶(CA),在经胰蛋白酶处理从细胞质膜上释放出来后,仍保留其催化活性。当细胞外表面CA(简称细胞外CA)具活性时,可催化质膜外HCO_3~-与CO_2的相互转化,为Rubisco(磷酸核酮糖羧化酶)提供一稳定的CO_2流量环境,以维持正常的光合作用。     

Quantitative Analysis of Receptor Tyrosine Kinase-Effector Coupling at Functionally Relevant Stimulus Levels

A major goal of current signaling research is to develop a quantitative understanding of how receptor activation is coupled to downstream signaling events and to functional cellular responses. Here, we measure how activation of the RET receptor tyrosine kinase on mouse neuroblastoma cells by the neurotrophin artemin (ART) is quantitatively coupled to key downstream effectors. We show that the efficiency of RET coupling to ERK and Akt depends strongly on ART concentration, and it is highest at the low (∼100 pm) ART levels required for neurite outgrowth. Quantitative discrimination between ERK and Akt pathway signaling similarly is highest at this low ART concentration. Stimulation of the cells with 100 pm ART activated RET at the rate of ∼10 molecules/cell/min, leading at 5–10 min to a transient peak of ∼150 phospho-ERK (pERK) molecules and ∼50 pAkt molecules per pRET, after which time the levels of these two signaling effectors fell by 25–50% while the pRET levels continued to slowly rise. Kinetic experiments showed that signaling effectors in different pathways respond to RET activation with different lag times, such that the balance of signal flux among the different pathways evolves over time. Our results illustrate that measurements using high, super-physiological growth factor levels can be misleading about quantitative features of receptor signaling. We propose a quantitative model describing how receptor-effector coupling efficiency links signal amplification to signal sensitization between receptor and effector, thereby providing insight into design principles underlying how receptors and their associated signaling machinery decode an extracellular signal to trigger a functional cellular outcome.     

Solvent-induced differentiation of protein backbone hydrogen bonds in calmodulin

In apo and holoCaM, almost half of the hydrogen bonds (H-bonds) at the protein backbone expected from the corresponding NMR or X-ray structures were not detected by h3JNC' couplings. The paucity of the h3JNC' couplings was considered in terms of dynamic features of these structures. We examined a set of seven proteins and found that protein-backbone H-bonds form two groups according to the h3JNC' couplings measured in solution. H-bonds that have h3JNC' couplings above the threshold of 0.2 Hz show distance/angle correlation among the H-bond geometrical parameters, and appear to be supported by the backbone dynamics in solution. The other H-bonds have no such correlation; they populate the water-exposed and flexible regions of proteins, including many of the CaM helices. The observed differentiation in a dynamical behavior of backbone H-bonds in apo and holoCaM appears to be related to protein functions.     

State and Trait Olfactory Markers of Major Depression

Nowadays, depression is a major issue in public health. Because of the partial overlap between the brain structures involved in depression, olfaction and emotion, the study of olfactory function could be a relevant way to find specific cognitive markers of depression. This study aims at determining whether the olfactory impairments are state or trait markers of major depressive episode (MDE) through the study of the olfactory parameters involving the central olfactory pathway. In a pilot study, we evaluated prospectively 18 depressed patients during acute episodes of depression and 6 weeks after antidepressant treatment (escitalopram) against 54 healthy volunteers, matched by age, gender and smoking status. We investigated the participants’ abilities to identify odors (single odors and in binary mixture), to evaluate and discriminate the odors’ intensity, and determine the hedonic valence of odors. The results revealed an “olfactory anhedonia” expressed by decrease of hedonic score for high emotional odorant as potential state marker of MDE. Moreover, these patients experienced an “olfactory negative alliesthesia”, during the odor intensity evaluation, and failed to identify correctly two odorants with opposite valences in a binary iso-mixture, which constitute potential trait markers of the disease. This study provides preliminary evidence for olfactory impairments associated with MDE (state marker) that are persistent after the clinical improvement of depressive symptoms (trait marker). These results could be explained by the chronicity of depression and/or by the impact of therapeutic means used (antidepressant treatment). They need to be confirmed particularly the ones obtained in complex olfactory environment which corresponds a more objective daily life situation.     

Hyporientalin A,an anti-<Emphasis Type="Italic">Candida</Emphasis> peptaibol from a marine <Emphasis Type="Italic">Trichoderma orientale</Emphasis>

A Trichoderma orientale strain LSBA1 was isolated from the Mediterranean marine sponge Cymbaxinella damicornis. The crude extract of T. orientale mycelium showed inhibitory activity against growth of Gram-positive and Gram-negative bacteria as well as clinical isolates of Candida albicans. Purification of the anti-Candida component was performed using a combination of open silica gel-60 column and reverse phase high performance liquid chromatography. The active compound called hyporientalin A has been identified as a peptaibol analogue of longibrachin-A-II using mass spectrometry. It exhibited fungicidal activity against clinical isolates of C. albicans with minimal inhibitory concentrations (MICs) ranging from 2.49 to 19.66 µM, comparable to that of the antifungal agent amphotericin B. Our data support the use of hyporientalin A as a promising new and efficient antifungal drug in the treatment of candidiasis while controlling toxicity.