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991.
Chiara Falciani Luisa Lozzi Simona Pollini Vincenzo Luca Veronica Carnicelli Jlenia Brunetti Barbara Lelli Stefano Bindi Silvia Scali Antonio Di Giulio Gian Maria Rossolini Maria Luisa Mangoni Luisa Bracci Alessandro Pini 《PloS one》2012,7(10)
The branched M33 antimicrobial peptide was previously shown to be very active against Gram-negative bacterial pathogens, including multidrug-resistant strains. In an attempt to produce back-up molecules, we synthesized an M33 peptide isomer consisting of D-aminoacids (M33-D). This isomeric version showed 4 to 16-fold higher activity against Gram-positive pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, than the original peptide, while retaining strong activity against Gram-negative bacteria. The antimicrobial activity of both peptides was influenced by their differential sensitivity to bacterial proteases. The better activity shown by M33-D against S. aureus compared to M33-L was confirmed in biofilm eradication experiments where M33-L showed 12% activity with respect to M33-D, and in vivo models where Balb-c mice infected with S. aureus showed 100% and 0% survival when treated with M33-D and M33-L, respectively. M33-D appears to be an interesting candidate for the development of novel broad-spectrum antimicrobials active against bacterial pathogens of clinical importance. 相似文献
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993.
Leonardo Glutz von Blotzheim Felix C Tanner Georg Noll Matthias Brock Manuel Fischler Jürg Hafner Rudolf Speich Silvia Ulrich Lars C Huber 《Respiratory research》2012,13(1):45
Background
Martorell hypertensive ischemic leg ulcer (Martorell ulcer) is characterized by distinct alterations in the arteriolar wall of subcutaneous vessels, leading to progressive narrowing of the vascular lumen and increase of vascular resistance. These changes are similar to the alterations observed in pulmonary arterioles in patients with chronic pulmonary hypertension (PH). This study was aimed to assess an association between the two disorders.Methods
In this case–control study, 14 patients with Martorell ulcer were clinically assessed for the presence of pulmonary hypertension using transthoracic Doppler echocardiography. Data from patients were compared to 28 matched hypertensive controls.Results
Systolic pulmonary arterial pressure (sPAP) in patients with Martorell ulcer was significantly higher than in the control group (33.8 ± 16.9 vs 25.3 ± 6.5 mmHg, p = 0.023); the prevalence of pulmonary hypertension was 31% (5/14) in patients and 7% (2/28) in controls (p = 0.031). No differences were seen in left heart size and function between patients and controls.Conclusion
This study provides first evidence that subcutaneous arteriolosclerosis, the hallmark of Martorell ulcer, is associated with PH. These findings suggest that patients with Martorell leg ulcer might be at significant risk to develop elevated pulmonary arterial pressure. Patients with leg ulcers who present with dyspnea should be evaluated by echocardiography for the presence of pulmonary hypertension. 相似文献994.
M Gálvez-Santisteban AE Rodriguez-Fraticelli DM Bryant S Vergarajauregui T Yasuda I Bañón-Rodríguez I Bernascone A Datta N Spivak K Young CL Slim PR Brakeman M Fukuda KE Mostov F Martín-Belmonte 《Nature cell biology》2012,14(8):838-849
The formation of epithelial tissues requires both the generation of apical-basal polarity and the coordination of this polarity between neighbouring cells to form a central lumen. During de novo lumen formation, vectorial membrane transport contributes to the formation of a singular apical membrane, resulting in the contribution of each cell to only a single lumen. Here, from a functional screen for genes required for three-dimensional epithelial architecture, we identify key roles for synaptotagmin-like proteins 2-a and 4-a (Slp2-a/4-a) in the generation of a single apical surface per cell. Slp2-a localizes to the luminal membrane in a PtdIns(4,5)P(2)-dependent manner, where it targets Rab27-loaded vesicles to initiate a single lumen. Vesicle tethering and fusion is controlled by Slp4-a, in conjunction with Rab27/Rab3/Rab8 and the SNARE syntaxin-3. Together, Slp2-a/4-a coordinate the spatiotemporal organization of vectorial apical transport to ensure that only a single apical surface, and thus the formation of a single lumen, occurs per cell. 相似文献
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996.
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998.
Zanuy M Ramos-Montoya A Villacañas O Canela N Miranda A Aguilar E Agell N Bachs O Rubio-Martinez J Pujol MD Lee WN Marin S Cascante M 《Metabolomics : Official journal of the Metabolomic Society》2012,8(3):454-464
Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G(1) phase. Aberrant expression of CDK4 and CDK6 is a hallmark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM (the calcein acetoxymethyl-ester) is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G(1) phase. The metabolic effects of calcein AM on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phosphate pathway was significantly altered. To elucidate whether these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors. 相似文献
999.
Ganzella M Moreira JD Almeida RF Böhmer AE Saute JA Holmseth S Souza DO 《Purinergic signalling》2012,8(1):49-58
Overstimulation of the glutamatergic system (excitotoxicity) is involved in various acute and chronic brain diseases. Several
studies support the hypothesis that guanosine-5′-monophosphate (GMP) can modulate glutamatergic neurotransmission. The aim
of this study was to evaluate the effects of chronically administered GMP on brain cortical glutamatergic parameters in mice.
Additionally, we investigated the neuroprotective potential of the GMP treatment submitting cortical brain slices to oxygen
and glucose deprivation (OGD). Moreover, measurements of the cerebrospinal fluid (CSF) purine levels were performed after
the treatment. Mice received an oral administration of saline or GMP during 3 weeks. GMP significantly decreases the cortical
brain glutamate binding and uptake. Accordingly, GMP reduced the immunocontent of the glutamate receptors subunits, NR2A/B
and GluR1 (NMDA and AMPA receptors, respectively) and glutamate transporters EAAC1 and GLT1. GMP treatment significantly reduced
the immunocontent of PSD-95 while did not affect the content of Snap 25, GLAST and GFAP. Moreover, GMP treatment increased
the resistance of neocortex to OGD insult. The chronic GMP administration increased the CSF levels of GMP and its metabolites.
Altogether, these findings suggest a potential modulatory role of GMP on neocortex glutamatergic system by promoting functional
and plastic changes associated to more resistance of mice neocortex against an in vitro excitotoxicity event. 相似文献
1000.
Silvia Del Vecchio Emanuela Giovi Carmela Francesca Izzi Giovanna Abbate Alicia T.R. Acosta 《Journal for Nature Conservation》2012,20(6):357-363
We compared the coenological information of the only Italian population of Malcolmia littorea (L.) R. Br. with published phytosociological relevés, including ones of this species, throughout its European range. With the aim of highlighting the main climatic features influencing the distribution patterns of M. littorea, we integrated coenological data with some climatic variables and considered major drivers for plant distribution at the European scale. Finally, we analysed the population extent of M. littorea in Italy, in order to assess its conservation status at regional level. The DCA analysis, performed on a matrix 139 relevés × 183 species, separated the relevés according to their floristic composition, showing a geographic gradient from Portugal to Mediterranean coasts, until Italy; with Mediterranean relevés clearly separated from Atlantic ones as well. Along the beach-inland gradient, the analysis highlights that the species is typical of fixed dunes habitats (more inland, mainly stabilised dunes), although in the Atlantic it can also be found in mobile dunes. The analysis of climatic variables in relation to M. littorea distribution, suggested that the species is sensitive to low winter temperature and to summer drought. The only Italian population of M. littorea is subjected to many threats, due to its small dimensions (<1 ha), isolation from the rest of its distribution area, that ranges from Portugal to France (until the Camargue region) and intensive human disturbances. Using both field and remote sensing information, we showed a considerable decrease of the occupied surface in Italy, leading us to suggest that the IUCN threat category of M. littorea in Italy should be reassessed from endangered to critically endangered. 相似文献