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排序方式: 共有198条查询结果,搜索用时 15 毫秒
1.
Julie A. Harris Akihiko Koyama Sumihiro Maeda Kaitlyn Ho Nino Devidze Dena B. Dubal Gui-Qiu Yu Eliezer Masliah Lennart Mucke 《PloS one》2012,7(9)
Accumulation of hyperphosphorylated tau in the entorhinal cortex (EC) is one of the earliest pathological hallmarks in patients with Alzheimer’s disease (AD). It can occur before significant Aβ deposition and appears to “spread” into anatomically connected brain regions. To determine whether this early-stage pathology is sufficient to cause disease progression and cognitive decline in experimental models, we overexpressed mutant human tau (hTauP301L) predominantly in layer II/III neurons of the mouse EC. Cognitive functions remained normal in mice at 4, 8, 12 and 16 months of age, despite early and extensive tau accumulation in the EC. Perforant path (PP) axon terminals within the dentate gyrus (DG) contained abnormal conformations of tau even in young EC-hTau mice, and phosphorylated tau increased with age in both the EC and PP. In old mice, ultrastructural alterations in presynaptic terminals were observed at PP-to-granule cell synapses. Phosphorylated tau was more abundant in presynaptic than postsynaptic elements. Human and pathological tau was also detected within hippocampal neurons of this mouse model. Thus, hTauP301L accumulation predominantly in the EC and related presynaptic pathology in hippocampal circuits was not sufficient to cause robust cognitive deficits within the age range analyzed here. 相似文献
2.
Mavericks are virus-like mobile genetic elements found in the genomes of eukaryotes. Although Mavericks encode capsid morphogenesis homologs, their viral particles have not been observed. Here, we provide new evidence supporting the viral nature of Mavericks and the potential existence of virions. To this end, we conducted a phylogenomic analysis of Mavericks in hundreds of vertebrate genomes, discovering 134 elements with an intact coding capacity in 17 host species. We reveal an extensive genomic fossil record in 143 species and date three groups of elements to the Late Cretaceous. Bayesian phylogenetic analysis using genomic fossil orthologs suggests that Mavericks have infected osteichthyans for ∼419 My. They have undergone frequent cross-species transmissions in cyprinid fish and all core genes are subject to strong purifying selection. We conclude that vertebrate Mavericks form an ancient lineage of aquatic dsDNA viruses which are probably still functional in some vertebrate lineages. 相似文献
3.
Gregor Stiglic Petra Povalej Brzan Nino Fijacko Fei Wang Boris Delibasic Alexandros Kalousis Zoran Obradovic 《PloS one》2015,10(12)
Different studies have demonstrated the importance of comorbidities to better understand the origin and evolution of medical complications. This study focuses on improvement of the predictive model interpretability based on simple logical features representing comorbidities. We use group lasso based feature interaction discovery followed by a post-processing step, where simple logic terms are added. In the final step, we reduce the feature set by applying lasso logistic regression to obtain a compact set of non-zero coefficients that represent a more comprehensible predictive model. The effectiveness of the proposed approach was demonstrated on a pediatric hospital discharge dataset that was used to build a readmission risk estimation model. The evaluation of the proposed method demonstrates a reduction of the initial set of features in a regression model by 72%, with a slight improvement in the Area Under the ROC Curve metric from 0.763 (95% CI: 0.755–0.771) to 0.769 (95% CI: 0.761–0.777). Additionally, our results show improvement in comprehensibility of the final predictive model using simple comorbidity based terms for logistic regression. 相似文献
4.
Evelina Colacino Antonella Converso Antonio De Nino Antonella Leggio Angelo Liguori Loredana Maiuolo 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):581-583
Abstract The complete set of the 4′-aza analogues of 2′,3′-dideoxynucleosides was synthesized by cycloaddition of N-tetrahydropiranyl or N-trityl methylene nitrones on suitably protected vinyl nucleobases. The convertible nucleoside approach was used in the preparation of cytosine and 5-methyl cytosine analogues. 相似文献
5.
C.N. Holenstein C.R. Lendi Nino Wili 《Computer methods in biomechanics and biomedical engineering》2019,22(8):853-860
Measuring cell-generated forces by Traction Force Microscopy (TFM) has become a standard tool in cell mechanobiology. Although widely used in two dimensional (2D) experiments, only a few methods exist to measure traction in three-dimensional (3D) cell culture, since 3D volumetric high-resolution microscopy and more demanding computational approaches are required. Although it is commonly known that the selected experimental and computational setup highly influence the quality and accuracy of the results, no existing methods can adequately assess the errors involved in this process. We present a fully integrated simulation and evaluation platform that allows one to simulate TFM images and quantify errors of an applied approach for traction stress reconstruction, in order to improve experiments that attempt to measure mechanical interaction in cellular systems. In this context, we show that a careful parameter selection can decrease the reconstructed traction error by up to 40%. 相似文献
6.
Alberto Mu?oz Margherita Bertuzzi Jan Bettgenhaeuser Nino Iakobachvili Elaine M. Bignell Nick D. Read 《PloS one》2015,10(9)
Aspergillus fumigatus is an inhaled fungal pathogen of human lungs, the developmental growth of which is reliant upon Ca2+-mediated signalling. Ca2+ signalling has regulatory significance in all eukaryotic cells but how A. fumigatus uses intracellular Ca2+ signals to respond to stresses imposed by the mammalian lung is poorly understood. In this work, A. fumigatus strains derived from the clinical isolate CEA10, and a non-homologous recombination mutant ΔakuB
KU80, were engineered to express the bioluminescent Ca2+-reporter aequorin. An aequorin-mediated method for routine Ca2+ measurements during the early stages of colony initiation was successfully developed and dynamic changes in cytosolic free calcium ([Ca2+]c) in response to extracellular stimuli were measured. The response to extracellular challenges (hypo- and hyper-osmotic shock, mechanical perturbation, high extracellular Ca2+, oxidative stress or exposure to human serum) that the fungus might be exposed to during infection, were analysed in living conidial germlings. The ‘signatures’ of the transient [Ca2+]c responses to extracellular stimuli were found to be dose- and age-dependent. Moreover, Ca2+-signatures associated with each physico-chemical treatment were found to be unique, suggesting the involvement of heterogeneous combinations of Ca2+-signalling components in each stress response. Concordant with the involvement of Ca2+-calmodulin complexes in these Ca2+-mediated responses, the calmodulin inhibitor trifluoperazine (TFP) induced changes in the Ca2+-signatures to all the challenges. The Ca2+-chelator BAPTA potently inhibited the initial responses to most stressors in accordance with a critical role for extracellular Ca2+ in initiating the stress responses. 相似文献
7.
Nino Asatiani Tamar Kartvelishvili Marina Abuladze Lali Asanishvili Nelly Sapojnikova 《Biological trace element research》2011,142(3):388-397
The changes in glutathione-dependent cycle enzymes and catalase activities under Cr(VI)-induced oxidative stress were investigated
in two distinct cell lines: L-41−human epithelial-like cells and HLF−fetal human diploid lung fibroblasts, which differ in
tissue origin, proliferation, and antioxidant enzymes activities. The chromium concentrations from 1 to 5 μM cause nontoxic
effects and activate antioxidant enzymes to overcome oxidative stress. In spite of some differences in the endogenous antioxidant
activities, both cell lines reveal the same range of toxic concentrations (20–30 μM). The irreversible inhibition of glutathione-dependent
antioxidant enzymes develops under toxic concentrations and serves as a marker of toxicity. The endogenous antioxidant activity
influences time-dependent expression of Cr(VI) toxicity and the dynamics of antioxidant enzymes activity under nontoxic conditions.
The cell antioxidant defense system is an important marker of the cell adaptive capacity under nontoxic and toxic conditions. 相似文献
8.
Irene Faravelli Megi Meneri Domenica Saccomanno Daniele Velardo Elena Abati Delia Gagliardi Valeria Parente Lucia Petrozzi Dario Ronchi Nino Stocchetti Edoardo Calderini Grazia D’Angelo Giovanna Chidini Edi Prandi Giulia Ricci Gabriele Siciliano Nereo Bresolin Giacomo Pietro Comi Stefania Corti Francesca Magri Alessandra Govoni 《Journal of cellular and molecular medicine》2020,24(5):3034-3039
The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response. 相似文献
9.
Vladimir Elisashvili Eva Kachlishvili Nino Tsiklauri Eka Metreveli Tamar Khardziani Spiros N. Agathos 《World journal of microbiology & biotechnology》2009,25(2):331-339
The production of lignocellulolytic enzymes by eleven basidiomycetes species isolated from two ecosystems of Georgia was investigated
for the first time under submerged (SF) and solid-state fermentation (SSF) of lignocellulosic by-products. Notable intergeneric
and intrageneric differences were revealed with regard to the extent of hydrolase and oxidase activity. Several fungi produced
laccase along with hydrolases in parallel with growth during the trophophase, showing that the synthesis of this enzyme is
not connected with secondary metabolism. The lignocellulosic substrate type had the greatest impact on enzyme secretion. Some
of the substrates significantly stimulated lignocellulolytic enzyme synthesis without supplementation of the culture medium
with specific inducers. Exceptionally high carboxymethyl cellulase (CMCase, 122 U ml−1) and xylanase (195 U ml−1) activities were revealed in SF of mandarin peelings by Pseudotremella gibbosa IBB 22 and of residue after ethanol production (REP) by Fomes fomentarius IBB 38, respectively. The SSF of REP by T. pubescens IBB 11 ensured the highest level of laccase activity (24,690 U l−1), whereas the SSF of wheat bran and SF of mandarin peels provided the highest manganese peroxidase activity (570–620 U l−1) of Trichaptum biforme IBB 117. Moreover, the variation of lignocellulosic growth substrate provides an opportunity to obtain enzyme preparations
containing different ratios of individual enzymes. 相似文献
10.
Jennifer A. Whitaker Veriko Mirtskhulava Maia Kipiani Drew A. Harris Nino Tabagari Russell R. Kempker Henry M. Blumberg 《PloS one》2013,8(3)