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91.
Granchi C Roy S Mottinelli M Nardini E Campinoti F Tuccinardi T Lanza M Betti L Giannaccini G Lucacchini A Martinelli A Macchia M Minutolo F 《Bioorganic & medicinal chemistry letters》2011,21(24):7331-7336
N-Hydroxyindole-2-carboxylates possessing sulfonamide-substituents at either position 5 or 6 were designed and synthesized. The inhibitory activities of these compounds against isoforms 1 and 5 of human lactate dehydrogenase were analysed, and Ki values of the most efficient inhibitors were determined by standard enzyme kinetic studies. Some of these compounds displayed state-of-the-art inhibitory potencies against isoform 5 (Ki values as low as 5.6 μM) and behaved as competitive inhibitors versus both the substrate and the cofactor. 相似文献
92.
93.
Taddei ML Parri M Angelucci A Bianchini F Marconi C Giannoni E Raugei G Bologna M Calorini L Chiarugi P 《Molecular cancer research : MCR》2011,9(2):149-160
EphA2 kinase regulates cell shape, adhesion, and motility and is frequently overexpressed in several cancers, including melanoma, prostate, breast, and colon cancers and lung carcinoma. Although a function in both tumor onset and metastasis has been proposed, the role played by EphA2 in tumor progression is still debated. In melanoma, EphA2 has been reported to affect cell migration and invasiveness allowing cells to move by a proteolysis-independent strategy, commonly referred as amoeboid motility. With the aim to understand the role of EphA2 in prostate cancer metastatic spreading, we stably silenced EphA2 expression in a model of aggressive metastatic prostate carcinoma. Our results show that EphA2 drives the metastatic program of prostate carcinoma, although its involvement greatly differs among metastatic steps. Indeed, EphA2 expression (i) greatly affects prostate carcinoma cell motility style, guiding an amoeboid movement based on Rho-mediated cell rounding and independent from metalloprotases, (ii) is ineffective on transendothelial migration, adhesion onto extracellular matrix proteins, and on resistance to anoikis, (iii) regulates clonogenic potential of prostate carcinoma, thereby increasing anchorage-independent growth and self-renewal, prostasphere formation, tumor onset, dissemination to bone, and growth of metastatic colonies. Our finding indicate that EphA2-overexpressing prostate carcinoma cells gain an invasive benefit from their amoeboid motility style to escape from primary tumors and then, enhancing their clonogenic potential successfully target bone and grow metastases, thereby acknowledging EphA2 as a target for antimetastatic therapy of aggressive prostate cancers. 相似文献
94.
Haybaeck J Heikenwalder M Klevenz B Schwarz P Margalith I Bridel C Mertz K Zirdum E Petsch B Fuchs TJ Stitz L Aguzzi A 《PLoS pathogens》2011,7(1):e1001257
Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrP(C), efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrP(C) selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrP(Sc) and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories. 相似文献
95.
Jacob I. Ayers Charles R. Schutt Ronald A. Shikiya Adriano Aguzzi Anthony E. Kincaid Jason C. Bartz 《PLoS pathogens》2011,7(3)
Prion strains are characterized by differences in the outcome of disease, most notably incubation period and neuropathological features. While it is established that the disease specific isoform of the prion protein, PrPSc, is an essential component of the infectious agent, the strain-specific relationship between PrPSc properties and the biological features of the resulting disease is not clear. To investigate this relationship, we examined the amplification efficiency and conformational stability of PrPSc from eight hamster-adapted prion strains and compared it to the resulting incubation period of disease and processing of PrPSc in neurons and glia. We found that short incubation period strains were characterized by more efficient PrPSc amplification and higher PrPSc conformational stabilities compared to long incubation period strains. In the CNS, the short incubation period strains were characterized by the accumulation of N-terminally truncated PrPSc in the soma of neurons, astrocytes and microglia in contrast to long incubation period strains where PrPSc did not accumulate to detectable levels in the soma of neurons but was detected in glia similar to short incubation period strains. These results are inconsistent with the hypothesis that a decrease in conformational stability results in a corresponding increase in replication efficiency and suggest that glia mediated neurodegeneration results in longer survival times compared to direct replication of PrPSc in neurons. 相似文献
96.
Di Pierro Erica Ghisla Anne Wauters Lucas A. Molinari Ambrogio Martinoli Adriano Gurnell John Tosi Guido 《European Journal of Wildlife Research》2011,57(3):585-595
Space-use patterns of seed predators are strongly affected by spatiotemporal variation in the abundance of different tree
seeds, their major food source. However, most studies have measured relationships between overall food availability and space
use, and there are few cases where effects of different food resources have been explored. We studied the effects of two food
resources, Norway spruce and silver fir seeds, on space and habitat use in red squirrel in a subalpine conifer forest from
2000 to 2006. Fir seeds disperse in the autumn of the year they are produced, spruce the following spring. We estimated spruce
and fir seed availability within individual home ranges and monitored home-range size using radiotelemetry. Males had larger
home ranges than females and the sexes responded differently to variation in food and density. Spruce seed availability negatively
affected home-range and core-area sizes of males in spring–summer. Space use was not affected by fir seed availability. Squirrels
positively selected spruce for foraging and spruce was always preferred over fir. Our results showed that spruce, but not
fir, affected space and habitat use of squirrels, suggesting they do not behaviourally respond to early seed dispersal in
fir. 相似文献
97.
Francesco Bisi Mosé Nodari Nuno Miguel Dos Santos Oliveira Elisa Masseroni Damiano G. Preatoni Lucas A. Wauters Guido Tosi Adriano Martinoli 《European Journal of Wildlife Research》2011,57(2):305-312
Populations on the limits of species’ distribution can show different behavioral adaptations to strong ecological pressure
than in the central part of the range. We investigated space use patterns of alpine mountain hare (Lepus timidus) at two areas on the southern edge of the species’ range. We monitored 34 hares between 2005 and 2008, estimating home range
size, overlap, and site fidelity, and compared our results with space use in Scottish and North-European populations. Home
ranges of mountain hares did not differ between two study areas with different habitat types. Subadult animals used larger
ranges than adults and both age groups reduced home range size in autumn, a period that might be critical for hares due to
changes in diet and/or high energy expenditure during the previous breeding season. Home ranges in these alpine populations
were smaller than in Scandinavian populations but within the range of populations in different habitat types in Scotland.
Seasonal home ranges overlapped considerably, but differed among the sexes: male–female overlap was higher than same sex (male–male
and female–female) spatial overlap. Seasonal shifts of home ranges were small, and site fidelity remained high over the seasons,
suggesting that resource distribution remained constant throughout the year and that the knowledge of an intensively frequented
area is an important element of habitat quality. We concluded that habitat structure and availability of mates interact in
affecting mountain hare space use in alpine habitats. 相似文献
98.
Giuseppe Maria Carpaneto Adriano Mazziotta Paolo Maltzeff 《Journal of Insect Conservation》2011,15(6):833-837
We attempt to identify the threat to flying beetles imposed by mist nets deployed for bird studies in an area of Mediterranean
mosaic of evergreen scrub and deciduous forest in Italy. The present paper is the first attempt to identify the non-target
species which die in these artificial traps. A large number of large scarab beetles was entangled in mist nets during a complete
ringing session. The seasonal trend of beetle populations and their daily flight activity were also recorded. The results
lead us to suggest that the populations of some threatened dung beetles can be impoverished at local level and represent a
bycatch of mist net techniques, especially in early spring and at sunrise, when their swarming and reproductive activity is
high. When summed with other factors affecting these beetles, such as habitat loss and fragmentation, this tool may represent
a threat for vulnerable insect populations. Trapping effects may also represent a depletion of food resource for some insectivorous
birds. For these reasons we recommend cooperative research between ornithologists and entomologists to fully study the bycatch
effects of mist netting on flying insects and their effects on food availability for insectivorous birds. 相似文献
99.
The Brazilian Atlantic Forest is a Biodiversity Hotspot, yet many biological groups in this biome are poorly known. We compiled
information on the diversity of Atlantic Forest tiger moths (Arctiidae) and assessed the resemblance among localities, whether
arctiid assemblages are concordant with major vegetation types, and the importance of environmental factors in structuring
the variation among assemblages. Additionally, we developed a procedure composed of subsampling and procrustean analysis to
assess the robustness of the results from community composition ordinations when localities differ in species richness. To
do this, we built a database from specimens deposited in the ten most important Brazilian entomological collections, and mapped
species richness in one-degree latitude/longitude grid cells. We employed Principal Coordinates Analysis to assess similarities
among the best-sampled localities. We obtained 8,667 records including 1,193 species, representing 60 and 20% of the estimated
Brazilian and Neotropical faunas, respectively. Our subsampling procedure indicated that the ordination was not greatly affected
by differences in species richness, and was congruent with major vegetation types. Lowland localities on the seacoast were
quite distinct in species composition. A second group included localities in montane areas in the southeast part of the biome.
The last group included localities in the southern region and those with Araucaria forests, and was associated with long distances
from the ocean, even distribution of precipitation throughout the year, and large annual temperature ranges. 相似文献
100.
Dragisic C Ashkenazi E Bede L Honzák M Killeen T Paglia A Semroc B Savy C 《Journal of industrial microbiology & biotechnology》2011,38(2):371-374
Increasingly, government regulations, voluntary standards, and company guidelines require that biofuel production complies with sustainability criteria. For some stakeholders, however, compliance with these criteria may seem complex, costly, or unfeasible. What exiting tools, then, might facilitate compliance with a variety of biofuel-related sustainability criteria? This paper presents four existing tools and methodologies that can help stakeholders assess (and mitigate) potential risks associated with feedstock production, and can thus facilitate compliance with requirements under different requirement systems. These include the Integrated Biodiversity Assessment Tool (IBAT), the ARtificial Intelligence for Ecosystem Services (ARIES) tool, the Responsible Cultivation Areas (RCA) methodology, and the related Biofuels + Forest Carbon (Biofuel + FC) methodology. 相似文献