Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level.

The serine/threonine kinase AKT/PKB plays a fundamental role in a wide variety of neuronal functions, including neuronal cell development, axonal growth, and synaptic plasticity. Multiple evidence link AKT signaling pathways to regulation of late phase long-term synaptic plasticity, synaptogenesis, and spinogenesis, as well as long-term memory formation. Nevertheless, the downstream effectors mediating the effects of AKT on early phase long-term potentiation (eLTP) are currently unknown. Here we report that using different regimes of pharmacological activation and inhibition of AKT activity in acute hippocampal slices, we found that AKT regulates the post-synaptic expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptors affecting solely the expression of eLTP, with no effect on its induction and maintenance. We further show that both maintenance of basal synaptic activity and expression of eLTP require plasma membrane tethering by activated AKT and that basal synaptic activity may be regulated via the direct effects of AKT1 on the expression level of post-synaptic AMPA receptors bypassing the canonical AKT signaling. Finally, we establish that eLTP expression requires the involvement of both the canonical AKT signaling pathways and the direct effect of AKT1 on AMPA receptor activity/expression in the post-synaptic membrane. © 2016 Wiley Periodicals, Inc.

Acute hypoxia enhances proteins' S-nitrosylation in endothelial cells.

Hypoxia-induced responses are frequently encountered during cardiovascular injuries. Hypoxia triggers intracellular reactive oxygen species/nitric oxide (NO) imbalance. Recent studies indicate that NO-mediated S-nitrosylation (S-NO) of cysteine residue is a key posttranslational modification of proteins. We demonstrated that acute hypoxia to endothelial cells (ECs) transiently increased the NO levels via endothelial NO synthase (eNOS) activation. A modified biotin-switch method coupled with Western blot on 2-dimensional electrophoresis (2-DE) demonstrated that at least 11 major proteins have significant increase in S-NO after acute hypoxia. Mass analysis by CapLC/Q-TOF identified those as Ras-GTPase-activating protein, protein disulfide-isomerase, human elongation factor-1-delta, tyrosine 3/tryptophan 5-monooxygenase activating protein, and several cytoskeleton proteins. The S-nitrosylated cysteine residue on tropomyosin (Cys 170) and beta-actin (Cys 285) was further verified with the trypsic peptides analyzed by MASCOT search program. Further understanding of the functional relevance of these S-nitrosylated proteins may provide a molecular basis for treating ischemia-induced vascular disorders.

Mass spectra of N-substituted cantharidinimides.

The mass spectra of a series of N-substituted cantharidinimides were examined. The feature of this series compounds is a sequential double hydrogen transfer from the oxabicycloheptane unit to either the carbonyl group of the succinimide unit or the nitrogen atom of the pyridyl or thiazolyl substituent through space. The ability of the N-substituent to accept a hydrogen atom possibly leads to the different fragmentation pathway.

[Epidemiologic studies on the role of tobacco in various human cancers]. / Etudes épidémiologiques sur le rôle du tabac dans les différents cancers humains

The totality of epidemiological research over the last 25 years in the field of the relationship between tobacco consumption and the chance of developing certain cancers has demonstrated beyond reasonable doubt that the use of tobacco is implicated in the genesis of a certain number of cancers of the respiratory tract and the upper air and food passages. The most important relationship concerns carcinoma of the bronchus, currently the most frequently encountered in men, for which the incidence risk is directly related to the use of cigarettes and which rises with the amount smoked and with inhaling. Other possible aetiological factors, particularly occupational exposure to chemical and radio active agents, whilst interesting are none the less marginal. The ramifications of epidemiologic and experimental researchs lead us to envisage a multifactorial aetiology in which tobacco is a constant element. Avoidance of exposure would play a major role in prevention.

[Mammary carcinoma: prognosis value of intra-mammary spread (author's transl)]. / Carcinomes du sein. Intérêt pronostique des disséminations intra-mammaires.

At the conclusion of this study based on 327 cases of breast cancer T1, T2 T3 (less than 7 cm) No, N1, Mo Pev O, treated by mastectomy and axillary dissection without previous treatment, it appears that the microscopic dissemination to the nipple has a pejorative prognosis value. The 5 years is 84 p. 100 when there is no nipple dissemination, 74 p. 100 when there is an intraductal nipple dissemination, and 57 p. 100 when there is lymphatic or interstitial nipple dissemination. These differences have a statistical value. This value does not seem connected with other pathological prognosis factors: tumors size, Bloom histopronostic grading, and the number of nodes invaded. The intra-mammary spread without nipple involvment has no prognostical value.

[Cancer mortality in France. New Aspects of the presentation and analysis of data]. / La Mortalité par cancer en France. Aspects nouveaux de présentation et d'analyse des données

In France mortality statistics are the only complete source of information on cancer. Investigation of the annual figures and the application of statistical methods to their presentation and analysis has facilitated fresh studies of geographical pathology, utilizing methods of analysis with simple and multiple correlations (analysis of correlations). Certain groupings were thus revealed, notably in the case of death from bronchial carcinoma, urinary bladder and gall bladder. Two groups of departements appeared the nearest to the national levels for deaths from cancer for all body sites.

[Effect of buyang huanwu decoction on the antithrombotic functions of the vessel wall].

The effects of Buyang Huanwu Decoction (BYHWD) on the antithrombotic functions of vessel wall were studied with human umbilical vein perfusion. It was observed that the both of Von Willebrand factor release stimulated by thrombin from the vessel walls and conversion of fibrinogen to fibrin catalyzed by thrombin were inhibited by BYHWD. There were no obvious effects of BYHWD on the thrombin adsorption to the vessel walls and the thrombin induced release of PGI2 as well as fibrinolysis inhibiting activity from the vessel walls.

[Clinical application of the serial flap pedicled with posterior interosseous artery and its recurrent branch].

OBJECTIVE: To explore a new surgical approach to repair skin and soft tissue defect of hands. METHODS: Based on the anatomical study of the origin, course, branch, distribution, and anastomosis of the posterior interosseous artery and its recurrent branches in 40 upper limbs of cadavers, the posterior forearm serial flap, pedicled with the posterior interosseous artery and its recurrent branches, was designed and applied clinically in 17 cases to repair the skin and soft tissue defect of hands from August 1998 to July 2000. The size of flaps ranged from 7 cm x 5 cm to 15 cm x 10 cm. All of the cases were followed up for 3 weeks to 6 months. RESULTS: The anatomy study showed that the posterior forearm serial flap had long vascular pedicle, suitable thickness and large skin area. The clinical application indicated that the flaps survived in 16 cases. But flap necrosis at the distal end, sized 2 cm x 3 cm, was observed in one case, in which the defect was repaired by delayed skin grafting, CONCLUSION: The posterior forearm serial flap pedicled with the posterior interosseous artery and its recurrent branch have the character of avoidance of sacrificing the major arteries of the extremity, longer vascular pedicle, larger area and suitable thickness. The posterior forearm serial flap is a safe and easily manipulated surgical approach to repair the skin and soft tissue defect of the hands, especially of the thumb, palm, and proximal part of the fingers.