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931.
Antonio Di Stefano Eleonora D'Aurizio Oriana Trubiani Rossella Grande Emanuela Di Campli Mara Di Giulio Soraya Di Bartolomeo Piera Sozio Antonio Iannitelli Antonia Nostro Luigina Cellini 《Microbial biotechnology》2009,2(6):634-641
The viscoelastic properties of mono‐microbial biofilms produced by ocular and reference staphylococcal strains were investigated. The microorganisms were characterized for their haemolytic activity and agr typing and the biofilms, grown on stainless steel surface under static conditions, were analysed by Confocal Laser Scanning Microscopy. Static and dynamic rheometric tests were carried out to determine the steady‐flow viscosity and the elastic and viscous moduli. The analysed biofilms showed the typical time‐dependent behaviour of viscoelastic materials with considerable elasticity and mechanical stability except for Staphylococcus aureus ATCC 29213 biofilm which showed a very fragile structure. In particular, S. aureus 6ME biofilm was more compact than other staphylococcal biofilms studied with a yield stress ranging between 2 and 3 Pa. The data obtained in this work could represent a starting point for developing new therapeutic strategies against biofilm‐associated infections, such as improving the drug effect by associating an antimicrobial agent with a biofilm viscoelasticity modifier. 相似文献
932.
Anna M. Mileo Claudia Abbruzzese Stefano Mattarocci Emanuele Bellacchio Paola Pisano Antonio Federico Vittoria Maresca Mauro Picardo Alessandra Giorgi Bruno Maras M. Eugenia Schininà Marco G. Paggi 《PloS one》2009,4(10)
Background
Human Papillomavirus (HPV)-16 is a paradigm for “high-risk” HPVs, the causative agents of virtually all cervical carcinomas. HPV E6 and E7 viral genes are usually expressed in these tumors, suggesting key roles for their gene products, the E6 and E7 oncoproteins, in inducing malignant transformation.Methodology/Principal Findings
By protein-protein interaction analysis, using mass spectrometry, we identified glutathione S-transferase P1-1 (GSTP1) as a novel cellular partner of the HPV-16 E7 oncoprotein. Following mapping of the region in the HPV-16 E7 sequence that is involved in the interaction, we generated a three-dimensional molecular model of the complex between HPV-16 E7 and GSTP1, and used this to engineer a mutant molecule of HPV-16 E7 with strongly reduced affinity for GSTP1.When expressed in HaCaT human keratinocytes, HPV-16 E7 modified the equilibrium between the oxidized and reduced forms of GSTP1, thereby inhibiting JNK phosphorylation and its ability to induce apoptosis. Using GSTP1-deficient MCF-7 cancer cells and siRNA interference targeting GSTP1 in HaCaT keratinocytes expressing either wild-type or mutant HPV-16 E7, we uncovered a pivotal role for GSTP1 in the pro-survival program elicited by its binding with HPV-16 E7.Conclusions/Significance
This study provides further evidence of the transforming abilities of this oncoprotein, setting the groundwork for devising unique molecular tools that can both interfere with the interaction between HPV-16 E7 and GSTP1 and minimize the survival of HPV-16 E7-expressing cancer cells. 相似文献933.
Background
Large-scale sequencing projects have now become routine lab practice and this has led to the development of a new generation of tools involving function prediction methods, bringing the latter back to the fore. The advent of Gene Ontology, with its structured vocabulary and paradigm, has provided computational biologists with an appropriate means for this task.Methodology
We present here a novel method called ARGOT (Annotation Retrieval of Gene Ontology Terms) that is able to process quickly thousands of sequences for functional inference. The tool exploits for the first time an integrated approach which combines clustering of GO terms, based on their semantic similarities, with a weighting scheme which assesses retrieved hits sharing a certain number of biological features with the sequence to be annotated. These hits may be obtained by different methods and in this work we have based ARGOT processing on BLAST results.Conclusions
The extensive benchmark involved 10,000 protein sequences, the complete S. cerevisiae genome and a small subset of proteins for purposes of comparison with other available tools. The algorithm was proven to outperform existing methods and to be suitable for function prediction of single proteins due to its high degree of sensitivity, specificity and coverage. 相似文献934.
Stefano Pluchino Lucia Zanotti Elena Brambilla Patrizia Rovere-Querini Annalisa Capobianco Clara Alfaro-Cervello Giuliana Salani Chiara Cossetti Giovanna Borsellino Luca Battistini Maurilio Ponzoni Claudio Doglioni Jose Manuel Garcia-Verdugo Giancarlo Comi Angelo A. Manfredi Gianvito Martino 《PloS one》2009,4(6)
Background
The systemic injection of neural stem/precursor cells (NPCs) provides remarkable amelioration of the clinico-pathological features of experimental autoimmune encephalomyelitis (EAE). This is dependent on the capacity of transplanted NPCs to engage concurrent mechanisms of action within specific microenvironments in vivo. Among a wide range of therapeutic actions alternative to cell replacement, neuroprotective and immune modulatory capacities of transplanted NPCs have been described. However, lacking is a detailed understanding of the mechanisms by which NPCs exert their therapeutic plasticity. This study was designed to identify the first candidate that exemplifies and sustains the immune modulatory capacity of transplanted NPCs.Methodology/Principal Findings
To achieve the exclusive targeting of the peripheral immune system, SJL mice with PLP-induced EAE were injected subcutaneously with NPCs and the treatment commenced prior to disease onset. NPC-injected EAE mice showed significant clinical improvement, as compared to controls. Exogenous NPCs lacking the expression of major neural antigens were reliably (and for long-term) found at the level of draining lymph nodes, while establishing sophisticated anatomical interactions with lymph node cells. Importantly, injected NPCs were never found in organs other than lymph nodes, including the brain and the spinal cord. Draining lymph nodes from transplanted mice showed focal up-regulation of major developmental stem cell regulators, such as BMP-4, Noggin and Sonic hedgehog. In lymph nodes, injected NPCs hampered the activation of myeloid dendritic cells (DCs) and steadily restrained the expansion of antigen-specific encephalitogenic T cells. Both ex vivo and in vitro experiments identified a novel highly NPC-specific–BMP-4-dependent–mechanism hindering the DC maturation.Conclusion/Significance
The study described herein, identifies the first member of the TGF β/BMP family of stem cell regulators as a novel tolerogenic factor released by NPCs. Full exploitation of this pathway as an efficient tool for vaccination therapy in autoimmune inflammatory conditions is underway. 相似文献935.
936.
Stefano Di Santo Zijiang Yang Moritz Wyler von Ballmoos Jan Voelzmann Nicolas Diehm Iris Baumgartner Christoph Kalka 《PloS one》2009,4(5)
Background
Current evidence suggests that endothelial progenitor cells (EPC) contribute to ischemic tissue repair by both secretion of paracrine factors and incorporation into developing vessels. We tested the hypothesis that cell-free administration of paracrine factors secreted by cultured EPC may achieve an angiogenic effect equivalent to cell therapy.Methodology/Principal Findings
EPC-derived conditioned medium (EPC-CM) was obtained from culture expanded EPC subjected to 72 hours of hypoxia. In vitro, EPC-CM significantly inhibited apoptosis of mature endothelial cells and promoted angiogenesis in a rat aortic ring assay. The therapeutic potential of EPC-CM as compared to EPC transplantation was evaluated in a rat model of chronic hindlimb ischemia. Serial intramuscular injections of EPC-CM and EPC both significantly increased hindlimb blood flow assessed by laser Doppler (81.2±2.9% and 83.7±3.0% vs. 53.5±2.4% of normal, P<0.01) and improved muscle performance. A significantly increased capillary density (1.62±0.03 and 1.68±0.05/muscle fiber, P<0.05), enhanced vascular maturation (8.6±0.3 and 8.1±0.4/HPF, P<0.05) and muscle viability corroborated the findings of improved hindlimb perfusion and muscle function. Furthermore, EPC-CM transplantation stimulated the mobilization of bone marrow (BM)-derived EPC compared to control (678.7±44.1 vs. 340.0±29.1 CD34+/CD45− cells/1×105 mononuclear cells, P<0.05) and their recruitment to the ischemic muscles (5.9±0.7 vs. 2.6±0.4 CD34+ cells/HPF, P<0.001) 3 days after the last injection.Conclusions/Significance
Intramuscular injection of EPC-CM is as effective as cell transplantation for promoting tissue revascularization and functional recovery. Owing to the technical and practical limitations of cell therapy, cell free conditioned media may represent a potent alternative for therapeutic angiogenesis in ischemic cardiovascular diseases. 相似文献937.
Franti?ek Balu?ka Stefano Mancuso Dieter Volkmann Peter W Barlow 《Plant signaling & behavior》2009,4(12):1121-1127
This year celebrates the 200th aniversary of the birth of Charles Darwin, best known for his theory of evolution summarized in On the Origin of Species. Less well known is that, in the second half of his life, Darwin’s major scientific focus turned towards plants. He wrote several books on plants, the next-to-last of which, The Power of Movement of Plants, published together with his son Francis, opened plants to a new view. Here we amplify the final sentence of this book in which the Darwins proposed that: “It is hardly an exaggeration to say that the tip of the radicle thus endowed [with sensitivity] and having the power of directing the movements of the adjoining parts, acts like the brain of one of the lower animals; the brain being seated within the anterior end of the body, receiving impressions from the sense-organs, and directing the several movements.” This sentence conveys two important messages: first, that the root apex may be considered to be a ‘brain-like’ organ endowed with a sensitivity which controls its navigation through soil; second, that the root apex represents the anterior end of the plant body. In this article, we discuss both these statements.Key words: auxin, cognition, plant neurobiology, plant tropisms, roots, sensory biology, signaling 相似文献
938.
939.
Anna Ghelli Anna Maria Porcelli Claudia Zanna Sara Vidoni Stefano Mattioli Anna Barbieri Luisa Iommarini Maria Pala Alessandro Achilli Antonio Torroni Michela Rugolo Valerio Carelli 《PloS one》2009,4(11)
Leber''s hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD) on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts) carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad implications for other neurodegenerative disorders such as Parkinson''s disease. 相似文献
940.
Federica Semprucci Paola Boi Anita Manti Anabella Covazzi Harriague Marco Rocchi Paolo Colantoni Stefano Papa Maria Balsamo 《Helgoland Marine Research》2010,64(2):101-115
Bacteria, meio- and macrofauna were investigated at different depths in a coastal area of the Central Adriatic Sea, yielding
information about the composition and abundance of the benthic community. In particular, 14 nematode genera were recorded
for the first time in the Upper Adriatic Sea. All communities resulted as being significantly different between inshore and
offshore stations, especially when the season interaction was considered. Sediment grain size seemed to be the main natural
variable, along with trophic resources, affecting the distribution and composition of these benthic components, whilst there
was no clear evidence of competition for food sources and predatory pressure between the communities. Meiofauna appeared the
most useful community for detecting disturbances and river influences. In particular, the lowest copepod abundance in the
shallow waters seemed to be related to a greater anthropogenic disturbance inshore, whilst meiofaunal abundance and diversity
together with the nematode maturity index suggest the influence of the Foglia and Metauro rivers and the small stream Arzilla. 相似文献