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181.
Badea CT Athreya KK Espinosa G Clark D Ghafoori AP Li Y Kirsch DG Johnson GA Annapragada A Ghaghada KB 《PloS one》2012,7(4):e34496
Purpose
To investigate the utility of a liposomal-iodinated nanoparticle contrast agent and computed tomography (CT) imaging for characterization of primary nodules in genetically engineered mouse models of non-small cell lung cancer.Methods
Primary lung cancers with mutations in K-ras alone (KrasLA1) or in combination with p53 (LSL-KrasG12D;p53FL/FL) were generated. A liposomal-iodine contrast agent containing 120 mg Iodine/mL was administered systemically at a dose of 16 µl/gm body weight. Longitudinal micro-CT imaging with cardio-respiratory gating was performed pre-contrast and at 0 hr, day 3, and day 7 post-contrast administration. CT-derived nodule sizes were used to assess tumor growth. Signal attenuation was measured in individual nodules to study dynamic enhancement of lung nodules.Results
A good correlation was seen between volume and diameter-based assessment of nodules (R2>0.8) for both lung cancer models. The LSL-KrasG12D;p53FL/FL model showed rapid growth as demonstrated by systemically higher volume changes compared to the lung nodules in KrasLA1 mice (p<0.05). Early phase imaging using the nanoparticle contrast agent enabled visualization of nodule blood supply. Delayed-phase imaging demonstrated significant differential signal enhancement in the lung nodules of LSL-KrasG12D;p53FL/FL mice compared to nodules in KrasLA1 mice (p<0.05) indicating higher uptake and accumulation of the nanoparticle contrast agent in rapidly growing nodules.Conclusions
The nanoparticle iodinated contrast agent enabled visualization of blood supply to the nodules during the early-phase imaging. Delayed-phase imaging enabled characterization of slow growing and rapidly growing nodules based on signal enhancement. The use of this agent could facilitate early detection and diagnosis of pulmonary lesions as well as have implications on treatment response and monitoring. 相似文献182.
Monteiro KM Cardoso MB Follmer C da Silveira NP Vargas DM Kitajima EW Zaha A Ferreira HB 《PLoS neglected tropical diseases》2012,6(3):e1551
Background
Antigen B (AgB) is the major protein secreted by the Echinococcus granulosus metacestode and is involved in key host-parasite interactions during infection. The full comprehension of AgB functions depends on the elucidation of several structural aspects that remain unknown, such as its subunit composition and oligomeric states.Methodology/Principal Findings
The subunit composition of E. granulosus AgB oligomers from individual bovine and human cysts was assessed by mass spectrometry associated with electrophoretic analysis. AgB8/1, AgB8/2, AgB8/3 and AgB8/4 subunits were identified in all samples analyzed, and an AgB8/2 variant (AgB8/2v8) was found in one bovine sample. The exponentially modified protein abundance index (emPAI) was used to estimate the relative abundance of the AgB subunits, revealing that AgB8/1 subunit was relatively overrepresented in all samples. The abundance of AgB8/3 subunit varied between bovine and human cysts. The oligomeric states formed by E. granulosus AgB and recombinant subunits available, rAgB8/1, rAgB8/2 and rAgB8/3, were characterized by native PAGE, light scattering and microscopy. Recombinant subunits showed markedly distinct oligomerization behaviors, forming oligomers with a maximum size relation of rAgB8/3>rAgB8/2>rAgB8/1. Moreover, the oligomeric states formed by rAgB8/3 subunit were more similar to those observed for AgB purified from hydatid fluid. Pressure-induced dissociation experiments demonstrated that the molecular assemblies formed by the more aggregative subunits, rAgB8/2 and rAgB8/3, also display higher structural stability.Conclusions/Significance
For the first time, AgB subunit composition was analyzed in samples from single hydatid cysts, revealing qualitative and quantitative differences between samples. We showed that AgB oligomers are formed by different subunits, which have distinct abundances and oligomerization properties. Overall, our findings have significantly contributed to increase the current knowledge on AgB expression and structure, highlighting issues that may help to understand the parasite adaptive response during chronic infection. 相似文献183.
Valencia C Arévalo J Dujardin JC Llanos-Cuentas A Chappuis F Zimic M 《PLoS neglected tropical diseases》2012,6(6):e1656
Background
Increased rates for failure in leishmaniasis antimony treatment have been recently recognized worldwide. Although several risk factors have been identified there is no clinical score to predict antimony therapy failure of cutaneous leishmaniasis.Methods
A case control study was conducted in Peru from 2001 to 2004. 171 patients were treated with pentavalent antimony and followed up to at least 6 months to determine cure or failure. Only patients with ulcerative cutaneous leishmaniasis (N = 87) were considered for data analysis. Epidemiological, demographical, clinical and laboratory data were analyzed to identify risk factors for treatment failure. Two prognostic scores for antimonial treatment failure were tested for sensitivity and specificity to predict antimony therapy failure by comparison with treatment outcome.Results
Among 87 antimony-treated patients, 18 (21%) failed the treatment and 69 (79%) were cured. A novel risk factor for treatment failure was identified: presence of concomitant distant lesions. Patients presenting concomitant-distant lesions showed a 30.5-fold increase in the risk of treatment failure compared to other patients. The best prognostic score for antimonial treatment failure showed a sensitivity of 77.78% and specificity of 95.52% to predict antimony therapy failure.Conclusions
A prognostic score including a novel risk factor was able to predict antimonial treatment failure in cutaneous leishmaniasis with high specificity and sensitivity. This prognostic score presents practical advantages as it relies on clinical and epidemiological characteristics, easily obtained by physicians or health workers, and makes it a promising clinical tool that needs to be validated before their use for developing countries. 相似文献184.
185.
Marco A. Molina-Montenegro Jorge Gallardo-Cerda T. S. M. Flores Cristian Atala 《Plant Ecology》2012,213(1):133-142
The upper and poleward limit of tree distribution are usually determined by abiotic factors such as low temperature and strong
winds. Thus, cold resistance is a key element for survival in high altitudes and latitudes where conditions can reduce plant
growth. A trade-off between resource allocation to cold resistance and growth could emerge in populations frequently exposed
to low temperatures like those in the treeline zone. We studied annual height growth and ice nucleation temperature in Nothofagus pumilio (Nothofagaceae) populations growing in its extremes of altitudinal distribution and in 3 sites situated on a latitudinal
gradient in the Chilean Andes. Additionally, gas exchange, water and nitrogen use efficiency and total soluble sugar (TSS)
were also measured as possible mechanisms for survival in high altitudes. Individuals from the treeline populations showed
lower annual height growth and lower ice nucleation temperatures compared with those from lower populations. In the same way,
individuals from more poleward populations showed lower annual height growth and lower ice nucleation temperatures. Gas exchange,
water and nitrogen use efficiency and TSS were also higher in the high altitude populations. The results obtained support
the hypothesis of trade-off, because the upper and poleward populations showed more cold resistance but a lower height growth.
Additionally, we show that cold resistance mechanisms do not impact the physiological performance, suggesting possible adaptation
of the high altitude populations. Low temperatures may be affecting cellular growth instead of photosynthesis, creating a
pool of carbohydrates that could participate in cold tolerance. Other abiotic and biotic factors should be also assessed to
fully understand the distributional range of Nothofagus species. 相似文献
186.
187.
Ricciardi M Malpeli G Bifari F Bassi G Pacelli L Nwabo Kamdje AH Chilosi M Krampera M 《PloS one》2012,7(5):e35639
Mesenchymal stromal cells (MSCs) reside in many organs including lung, as shown by their isolation from fetal lung tissues, bronchial stromal compartment, bronchial-alveolar lavage and transplanted lung tissues. It is still controversial whether lung MSCs can undergo mesenchymal-to-epithelial-transition (MET) and possess immune regulatory properties. To this aim, we isolated, expanded and characterized MSCs from normal adult human lung (lung-hMSCs) and compared with human bone marrow-derived MSCs (BM-hMSCs). Our results show that lung-MSCs reside at the perivascular level and do not significantly differ from BM-hMSCs in terms of immunophenotype, stemness gene profile, mesodermal differentiation potential and modulation of T, B and NK cells. However, lung-hMSCs express higher basal level of the stemness-related marker nestin and show, following in vitro treatment with retinoic acid, higher epithelial cell polarization, which is anyway partial when compared to a control epithelial bronchial cell line. Although these results question the real capability of acquiring epithelial functions by MSCs and the feasibility of MSC-based therapeutic approaches to regenerate damaged lung tissues, the characterization of this lung-hMSC population may be useful to study the involvement of stromal cell compartment in lung diseases in which MET plays a role, such as in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. 相似文献
188.
Lagos CF Araya-Secchi R Thomas P Pérez-Acle T Tapia RA Salas CO 《Journal of molecular modeling》2012,18(5):2055-2064
Trypanosoma cruzi glutamate cysteine ligase (TcGCL) is considered a potential drug target to develop novel antichagasic drugs. We have used
a variety of computational methods to investigate the interactions between TcGCL with Glutathione (GSH). The three-dimensional
structure of TcGCL was constructed by comparative modeling methods using the Saccharomyces cerevisiae glutamate cysteine ligase as template. Molecular dynamics simulations were used to validate the TcGCL model and to analyze
the molecular interactions with GSH. Using RMSD clustering, the most prevalent GSH binding modes were identified paying attention
to the residues involved in the molecular interactions. The GSH binding modes were used to propose pharmacophore models that
can be exploited in further studies to identify novel antichagasic compounds. 相似文献
189.
Elena Bassi Emanuela Donaggio Andrea Marcon Massimo Scandura Marco Apollonio 《Mammalian Biology》2012,77(5):369-376
Red fox (Vulpes vulpes) and wolf (Canis lupus) are two widespread opportunistic predators living in simpatry in many areas. Nonetheless, scarce information are available on their trophic interactions. We investigated food habits of these two carnivores in a mountain area in Italy and assessed the extent of their trophic niche overlap, focusing on the consumption of wild ungulates. Thereby we analyzed the content of 669 red fox scats and 253 wolf scats collected between May 2008 and April 2009. Red foxes resulted to have a more than three times higher niche breadth than wolves. Vegetables, small mammals, wild ungulates, and invertebrates were major items (altogether 92% of volume) of the red fox annual diet. On the contrary wolf annual diet relied on wild ungulates (94% of volume) with wild boar (Sus scrofa) being the main food item. The degree of trophic niche overlap between the two species was found to be low (Pianka's O = 0.356). Diet variation between the warm and the cold seasons was limited in both species, and higher in red fox than in wolf. The two canids appeared to use wild ungulates unevenly being the former more selective for younger preys, smaller in size (newborn piglets and roe deer Capreolus capreolus fawns), whereas the latter exhibited a preference for medium-sized and large ungulates (10–35 kg wild boar and adult roe deer). Even if wild ungulates represent the main shared food category, the different use of age/weight classes by the two predators, together with their possible consumption as carrions by red fox, suggests a very limited trophic competition between wolf and red fox.This study represents a contribution to the knowledge of trophic interaction in predator–prey systems where sympatric carnivores are present. 相似文献
190.
G?tz Palfner Valentina Valenzuela-Mu?oz Cristian Gallardo-Escarate Luís E. Parra José Becerra Mario Silva 《Mycological Progress》2012,11(3):733-739
Cordyceps cuncunae Palfner sp. nov. is reported from Valdivian rainforest in southern Chile, parasiting larvae of an unidentified ghost moth species (Lepidoptera, Hepialidae) which probably feed on roots of Laureliopsis philippiana. Morphology and anatomy of stromata as well as morphological and molecular characteristics of mycelium in pure culture which produces two anamorphs, one of them Lecanicillium-like, are described. The systematic position of the new taxon within the most recent generic concept is discussed. This is the first record of an endemic Cordyceps species from Chile. 相似文献