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91.
Dorothee Dormann Anja Capell Aaron M. Carlson Sunita S. Shankaran† Ramona Rodde Manuela Neumann‡ Elisabeth Kremmer§ Takashi Matsuwaki¶ Keitaro Yamanouchi¶ Masugi Nishihara¶ Christian Haass 《Journal of neurochemistry》2009,110(3):1082-1094
Neuronal and glial deposition of misfolded, proteolytically processed, polyubiquitinated and abnormally phosphorylated C-terminal fragments (CTFs) of the TAR DNA binding protein-43 (TDP-43) is a pathological hallmark of frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U) and certain cases of amyotrophic lateral sclerosis. We demonstrate that TDP-43 can be proteolytically processed by caspases upon induction of apoptosis to a major 35 kDa and a minor 25 kDa CTF. These fragments are initially soluble, but over time they accumulate as insoluble and pathologically phosphorylated derivatives. However, proteolytic processing appears not to be absolutely required for the deposition of insoluble TDP-43 species, since a caspase resistant mutant of TDP-43 is also converted into insoluble species. Phosphorylation at S409/410 apparently occurs late during the conversion of soluble to insoluble TDP-43, suggesting that phosphorylation is not a prerequisite for aggregation. Loss of function of the progranulin (PGRN) gene causes FTLD-U with TDP-43 positive inclusions and has been suggested to lead to caspase activation and subsequent TDP-43 processing. However, siRNA-mediated knockdown of PGRN in cell culture as well as a PGRN gene knockout in mice failed to cause the formation of the disease characterizing CTFs of TDP-43. Our findings therefore suggest that caspase-mediated processing generates CTFs of similar biochemical properties as those occurring in nuclear and cytoplasmic deposits of FTLD-U patients independent of PGRN levels. 相似文献
92.
Summary
dl-Malic acid grown cells of Candida sphaerica (anamorph of Kluyveromyces marxianus) formed a saturable transport system that mediated accumulative transport of l(-)malic acid with the following kinetic parameters at pH 5.0: V
max, 0.44 nmol l(-)malate·s-1 per milligram dry weight; K
m
,0.1 mM
l(-)malate. Initial uptake of the acid was accompanied by disappearance of extracellular protons, the rates of which followed Michaelis-Menten kinetics as a function of the acid concentration. Variation with extracellular pH of the K
m
values, calculated either as the concentrations of anions or of undissociated acid, pointed to anions as the transported form. Furthermore, accumulated free acid suffered rapid efflux after the addition of the protonophore carbonylcyanide-M-chlorophenyl-hydrazone (CCCP). These results suggested that the transport system was a dicarboxylate-proton symporter. The system was inducible and was subject to glucose repression. Succinic, fumaric, -ketoglutaric, oxaloacetic and d-malic acid, but not maleic, malonic, oxalic nor l(+)-tartaric acid, apparently used the same transport system since they acted as competitive inhibitors of l(-)malic acid transport and induced proton movements that followed Michaelis-Menten kinetics. Experiments with glucose-repressed cells showed that undissociated dicarboxylic acid (measured with labelled succinic acid) entered the cells slowly by simple diffusion. The permeability of the cells for undissociated acid increased exponentially with pH, the diffusion constant increasing 100-fold between pH 3.5 and 6.0. 相似文献
93.
94.
Jose Bras Isabel Alonso Clara Barbot Maria?Manuela Costa Lee Darwent Tatiana Orme Jorge Sequeiros John Hardy Paula Coutinho Rita Guerreiro 《American journal of human genetics》2015,96(3):474-479
Hereditary autosomal-recessive cerebellar ataxias are a genetically and clinically heterogeneous group of disorders. We used homozygosity mapping and exome sequencing to study a cohort of nine Portuguese families who were identified during a nationwide, population-based, systematic survey as displaying a consistent phenotype of recessive ataxia with oculomotor apraxia (AOA). The integration of data from these analyses led to the identification of the same homozygous PNKP (polynucleotide kinase 3′-phosphatase) mutation, c.1123G>T (p.Gly375Trp), in three of the studied families. When analyzing this particular gene in the exome sequencing data from the remaining cohort, we identified homozygous or compound-heterozygous mutations in five other families. PNKP is a dual-function enzyme with a key role in different pathways of DNA-damage repair. Mutations in this gene have previously been associated with an autosomal-recessive syndrome characterized by microcephaly; early-onset, intractable seizures; and developmental delay (MCSZ). The finding of PNKP mutations associated with recessive AOA extends the phenotype associated with this gene and identifies a fourth locus that causes AOA. These data confirm that MCSZ and some forms of ataxia share etiological features, most likely reflecting the role of PNKP in DNA-repair mechanisms. 相似文献
95.
The objective of this study was to evaluate differences in correlations among Biological Elements and environmental parameters
for different river types, analysed at two different spatial scales. A total of 82 sites, with at least good ecological status,
were sampled across Europe, representing three core river types: Mountain rivers (26 sites); Lowland rivers (29 sites) and
Mediterranean rivers (17 sites). At each site samples of macrophytes, macroinvertebrates and fishes were taken during spring,
following the methodological procedures established by the European STAR project. Environmental parameters were also recorded,
based on a site protocol developed by the European projects AQEM and STAR. Environmental parameters were divided into three
categories: aquatic habitats (mesohabitat scale), global features (reach scale) and obligatory typology parameters of Water
Framework Directive (WFD) (geographical scale). Data were analysed to evaluate at the two scales, first, relationships among
biological elements, and second, relationships between biological elements and environmental parameters. Within each river
type, correlation matrices (Bray–Curtis distance) were calculated separately for each biological element and for each category
of environmental parameters. All biological elements were correlated (p<0.01) to the larger spatial scale: macrophytes and macroinvertebrates are more correlated in lowland and mountain rivers,
while in Mediterranean rivers, fish and macrophytes presented higher correlations. These links tend to be consistent for different
spatial scales, except if they are weak on a larger regional scale, obligatory parameters of WFD were, in most cases, significantly
correlated with the three biological communities (p<0.05). Results at different spatial scales supported the hierarchical theory of river formation. Reach and mesohabitat environmental
parameters tend to explain aquatic communities at a lower spatial scale, while geographical parameters tend to explain the
communities at a major spatial scale. 相似文献
96.
Local and regional assessments of the impacts of plant invaders on vegetation structure and soil properties of Mediterranean islands 总被引:7,自引:0,他引:7
Montserrat Vilà Marc Tessier Carey M. Suehs Giuseppe Brundu Luisa Carta Alexandros Galanidis Philip Lambdon Manuela Manca Frédéric Médail Eva Moragues Anna Traveset reas Y. Troumbis Philip E. Hulme 《Journal of Biogeography》2006,33(5):853-861
Aims Although biological invasions occur throughout the world, and some invaders are widespread in many habitats, few studies on the ecological impact of invaders have examined multiple sites. We tested how the impact of three widespread plant invaders changed depending on the identity of the species and the invaded island. We also tested whether relative species loss was lower in species‐rich communities than in species‐poor ones. Location We conducted floristic surveys and soil analyses in eight Mediterranean Basin islands: Crete and Lesbos (Greece), Sardinia (Italy), Corsica, Bagaud and Porquerolles (France), and Mallorca and Menorca (Spain). Methods We compared native species richness and diversity, proportion of life forms, soil percentage nitrogen, percentage organic carbon, C/N, and soil pH in nearby paired plots of 2 × 2 m: one control and one invaded by either the deciduous tree Ailanthus altissima, the succulent subshrubs Carpobrotus spp. or the annual geophyte Oxalis pes‐caprae, across eight Mediterranean Basin islands. Results On average, the presence of invaders reduced species diversity, Carpobrotus spp. exhibiting the largest impact and Oxalis the least. However, the relative impact was island‐dependent, and was positively but weakly associated with the species richness of the recipient community. Therophytes were the life form that experienced the largest decrease across islands. The effects of invasion on soil properties were very variable. Total N changed (increased) only in plots invaded by Ailanthus, significantly decreasing the C/N ratio. The presence of this tree increased soil pH, whereas the opposite was found in plots invaded by the other two species. Organic C increased in plots invaded by Ailanthus and Carpobrotus species. Main conclusions By conducting an analysis at multiple sites, we found that the three plant invaders had an impact on plant community structure not entirely concordant with changes in soil properties. The impacts depended on the identity of the species and of the invaded island, suggesting that impact of invaders is context‐specific. The impact in terms of species loss was not lower in species‐rich than in species‐poor communities. 相似文献
97.
98.
99.
Antonia Nostro Roberto Scaffaro Giovanna Ginestra Manuela D’Arrigo Luigi Botta Andreana Marino Giuseppe Bisignano 《Applied microbiology and biotechnology》2010,87(2):729-737
The aim of this study was to evaluate the effect of poly-ethylene-co-vinyl acetate (EVA) films incorporating different concentrations
(0.1%, 0.5% and 1%) of nisin on the biofilm-forming ability of Listeria monocytogenes ATCC 7644, Staphylococcus aureus 815 and Staphylococcus epidermidis ATCC 35984. Nisin was incorporated into two grades of EVA (EVA14 and EVA28) in the melt during a common film-blowing operation.
The efficacy of EVA/nisin films was evaluated by biofilm biomass measurements and Live/Dead staining in combination with fluorescence
microscopy. In order to evaluate whether the nisin incorporation could modify the film surface properties, contact angle measurements
and scanning electron microscopy were performed. The results revealed the efficacy of EVA14/nisin films in reducing biofilm
formation on their surfaces with more evident effect for S. epidermidis than L. monocytogenes and S. aureus strains. In contrast, EVA28/nisin films showed unsatisfactory activity. Fluorescence microscopy confirmed poor biofilm formation
on EVA14/nisin films, also characterised by the presence of dead cells. The data presented in this study offer new potential
applications for developing strategies aimed to improve the effect of antimicrobial agents. 相似文献
100.
María?F.?MonteroEmail author Manuela?Aristizábal Guillermo?García Reina 《Journal of applied phycology》2011,23(6):1053-1057
Biodiesel from algae is considered an alternative for a third generation of biofuels. However, most microalgae are not lipogenic
during fast growth periods, but high-lipid content occurs at resting stages. Microalgae biomass production for biodiesel needs
continuous high volumetric and aerial yields and large amount of neutral lipid in the biomass. These requirements are similar
to demanding a marathon runner to be obese. We show that by using cell sorting capabilities of flow cytometers, in combination
with the lipid-soluble fluorescent dye Nile Red, we can isolate and select cells with a high and stable lipid content. In
our study, we were able to select the equivalent of a stable “fat marathon runner” through three sorting events obtained from
wild populations of Tetraselmis suecica. 相似文献