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81.
82.
Florian MC Dörr K Niebel A Daria D Schrezenmeier H Rojewski M Filippi MD Hasenberg A Gunzer M Scharffetter-Kochanek K Zheng Y Geiger H 《Cell Stem Cell》2012,10(5):520-530
Highlights? Constitutively increasing Cdc42 activity causes aging of young HSCs ? Elevated Cdc42 activity correlates with a loss of cell polarity in aged HSCs ? Inhibition of Cdc42 activity rejuvenates aged LT-HSC function ? Cdc42 inhibition restores the level and spatial distribution of AcH4K16 相似文献
83.
An inventory of the woodlice fauna of the former USSR yielded 190 species, 64 of them were recorded from the territory of Russia. According to the cartographic analysis, the limits of distribution of epigean terrestrial isopods over the area, excluding mountains, is explained by temperature. No woodlice records were found outside the isocline of 120 days a year with the mean daily air temperature >10°C. The highest species diversity was found between the isoclines of 180 and 210 days. These areas correspond to forest-steppe and steppe zones. 相似文献
84.
González I Rakitina D Semashko M Taliansky M Praveen S Palukaitis P Carr JP Kalinina N Canto T 《RNA (New York, N.Y.)》2012,18(4):771-782
Previously, we found that silencing suppression by the 2b protein and six mutants correlated both with their ability to bind to double-stranded (ds) small RNAs (sRNAs) in vitro and with their nuclear/nucleolar localization. To further discern the contribution to suppression activity of sRNA binding and of nuclear localization, we have characterized the kinetics of in vitro binding to a ds sRNA, a single-stranded (ss) sRNA, and a micro RNA (miRNA) of the native 2b protein and eight mutant variants. We have also added a nuclear export signal (NES) to the 2b protein and assessed how it affected subcellular distribution and suppressor activity. We found that in solution native protein bound ds siRNA, miRNA, and ss sRNA with high affinity, at protein:RNA molar ratios ~2:1. Of the four mutants that retained suppressor activity, three showed sRNA binding profiles similar to those of the native protein, whereas the remaining one bound ss sRNA at a 2:1 molar ratio, but both ds sRNAs with 1.5-2 times slightly lower affinity. Three of the four mutants lacking suppressor activity failed to bind to any sRNA, whereas the remaining one bound them at far higher ratios. NES-tagged 2b protein became cytoplasmic, but suppression activity in patch assays remained unaffected. These results support binding to sRNAs at molar ratios at or near 2:1 as critical to the suppressor activity of the 2b protein. They also show that cytoplasmically localized 2b protein retained suppressor activity, and that a sustained nuclear localization was not required for this function. 相似文献
85.
Bonura C Di Carlo P Spicola D Cal C Mammina C Fasciana T Giammanco A 《The new microbiologica》2012,35(2):239-243
Recent reports indicate an increase in rates of infection and disease due to rapidly growing mycobacteria (RGM) in patients with pre-existing chronic lung disease. Studies have described difficulties in correctly identifying closely related species, even when proper methodologies are adopted, and several different gene targets have been proposed. We describe two cases of RGM infection in a 29-year-old HIV-1 positive Congolese man and a 19-year-old HIV-1 positive Liberian woman, respectively, both with bronchiectasis due to previous Mycobacterium tuberculosis (MTB) infection. Mycobacterium porcinum and Mycobacterium bolletii were identified in bronchoalveolar lavage fluid and sputum, respectively. After starting the patients on antiretroviral treatment and primary prophylaxis against non-tuberculous mycobacteria (NTM), and ensuring that they adhered to their prescribed regimen, we observed an improvement in their clinical condition and mycobacteria cleared from their respiratory specimens. Management of RGM respiratory infection in immunocompromised patients has to be evaluated on a case-by-case basis, taking into account the patient's pulmonary sequelae, adherence to multiple treatments and immune profile. 相似文献
86.
87.
D Yin WG Yang J Weissberg CB Goff W Chen Y Kuwayama A Leiter H Xing A Meixel D Gaut F Kirkbir D Sawcer PT Vernier JW Said MA Gundersen HP Koeffler 《PloS one》2012,7(8):e43891
Nanosecond pulsed electric fields (nsPEF) induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns). An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7–30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five other types of cancer cell lines were used to detect the effect of nsPEF in vitro. Rate of cell death in these 12 different cancer cell lines was dependent on nsPEF voltage and pulse number. To examine the effect of nsPEF in vivo, carcinogen-induced cutaneous papillomas and squamous cell carcinomas in mice were exposed to nsPEF with three pulse numbers (50, 200, and 400 pulses), two nominal electric fields (40 KV/cm and 31 KV/cm), and two pulse durations (7 ns and 14 ns). Carcinogen-induced cutaneous papillomas and squamous carcinomas were eliminated efficiently using one treatment of nsPEF with 14 ns duration pulses (33/39 = 85%), and all remaining lesions were eliminated after a 2nd treatment (6/39 = 15%). 13.5% of carcinogen-induced tumors (5 of 37) were eliminated using 7 ns duration pulses after one treatment of nsPEF. Associated with tumor lysis, expression of the anti-apoptotic proteins Bcl-xl and Bcl-2 were markedly reduced and apoptosis increased (TUNEL assay) after nsPEF treatment. nsPEF efficiently causes cell death in vitro and removes papillomas and squamous cell carcinoma in vivo from skin of mice. nsPEF has the therapeutic potential to remove human squamous carcinoma. 相似文献
88.
Meinzer M Flaisch T Seeds L Harnish S Antonenko D Witte V Lindenberg R Crosson B 《PloS one》2012,7(3):e33631
The neural basis of word-retrieval deficits in normal aging has rarely been assessed and the few previous functional imaging studies found enhanced activity in right prefrontal areas in healthy older compared to younger adults. However, more pronounced right prefrontal recruitment has primarily been observed during challenging task conditions. Moreover, increased task difficulty may result in enhanced activity in the ventral inferior frontal gyrus (vIFG) bilaterally in younger participants as well. Thus, the question arises whether increased activity in older participants represents an age-related phenomenon or reflects task difficulty effects. In the present study, we manipulated task difficulty during overt semantic and phonemic word-generation and used functional magnetic resonance imaging to assess activity patterns in the vIFG in healthy younger and older adults (N = 16/group; mean age: 24 vs. 69 years). Both groups produced fewer correct responses during the more difficult task conditions. Overall, older participants produced fewer correct responses and showed more pronounced task-related activity in the right vIFG. However, increased activity during the more difficult conditions was found in both groups. Absolute degree of activity was correlated with performance across groups, tasks and difficulty levels. Activity modulation (difficult vs. easy conditions) was correlated with the respective drop in performance across groups and tasks. In conclusion, vIFG activity levels and modulation of activity were mediated by performance accuracy in a similar way in both groups. Group differences in the right vIFG activity were explained by performance accuracy which needs to be considered in future functional imaging studies of healthy and pathological aging. 相似文献
89.
Marcello A. Mannino Giulio Catalano Sahra Talamo Giovanni Mannino Rosaria Di Salvo Vittoria Schimmenti Carles Lalueza-Fox Andrea Messina Daria Petruso David Caramelli Michael P. Richards Luca Sineo 《PloS one》2012,7(11)
Hunter-gatherers living in Europe during the transition from the late Pleistocene to the Holocene intensified food acquisition by broadening the range of resources exploited to include marine taxa. However, little is known on the nature of this dietary change in the Mediterranean Basin. A key area to investigate this issue is the archipelago of the Ègadi Islands, most of which were connected to Sicily until the early Holocene. The site of Grotta d’Oriente, on the present-day island of Favignana, was occupied by hunter-gatherers when Postglacial environmental changes were taking place (14,000-7,500 cal BP). Here we present the results of AMS radiocarbon dating, palaeogenetic and isotopic analyses undertaken on skeletal remains of the humans buried at Grotta d’Oriente. Analyses of the mitochondrial hypervariable first region of individual Oriente B, which belongs to the HV-1 haplogroup, suggest for the first time on genetic grounds that humans living in Sicily during the early Holocene could have originated from groups that migrated from the Italian Peninsula around the Last Glacial Maximum. Carbon and nitrogen isotope analyses show that the Upper Palaeolithic and Mesolithic hunter-gatherers of Favignana consumed almost exclusively protein from terrestrial game and that there was only a slight increase in marine food consumption from the late Pleistocene to the early Holocene. This dietary change was similar in scale to that at sites on mainland Sicily and in the rest of the Mediterranean, suggesting that the hunter-gatherers of Grotta d’Oriente did not modify their subsistence strategies specifically to adapt to the progressive isolation of Favignana. The limited development of technologies for intensively exploiting marine resources was probably a consequence both of Mediterranean oligotrophy and of the small effective population size of these increasingly isolated human groups, which made innovation less likely and prevented transmission of fitness-enhancing adaptations. 相似文献
90.
The pancreatic β-cell surface protein Tmem27 is promotes the preservation of functional β-cell mass. It is a selective substrate of the protease Bace2, yet the intramolecular features of Tmem27 that regulate its processing by this sheddase have not been characterized. In particular, the importance of homodimerization, glycosylation, trafficking to the plasma membrane (PM), the existence of multiple cleavage sites, and the amino acid residues that govern these features are currently unknown. Using Tmem27 mutational analysis and multiple biochemical approaches, we here show that Tmem27 dimerization is a dynamic process mediated by its intracellular cysteine residue and that prevents Tmem27 cleavage, that extracellular asparagine glycosylation is essential for Tmem27 trafficking to the PM and its processing by Bace2, that the amount of Tmem27 at the PM is proportional to its total cell levels upon glucose stimulation and Bace2 inhibition, and that the double phenylalanine motif in the Tmem27 cleavage site is an intramolecular Bace2 inhibitor. These findings define structural properties of Tmem27 that affect the susceptibility to its protease Bace2 and have implications for the efficiency with which Tmem27 and other Bace2 substrates are cleaved in normal and disease states. 相似文献