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191.
Angela Oppelt Viola H Lobert Kaisa Haglund Ashley M Mackey Lucia E Rameh Knut Liestøl Kay Oliver Schink Nina Marie Pedersen Eva M Wenzel Ellen M Haugsten Andreas Brech Tor Erik Rusten Harald Stenmark Jørgen Wesche 《EMBO reports》2013,14(1):57-64
Although phosphatidylinositol 5‐phosphate (PtdIns5P) is present in many cell types and its biogenesis is increased by diverse stimuli, its precise cellular function remains elusive. Here we show that PtdIns5P levels increase when cells are stimulated to move and we find PtdIns5P to promote cell migration in tissue culture and in a Drosophila in vivo model. First, class III phosphatidylinositol 3‐kinase, which produces PtdIns3P, was shown to be involved in migration of fibroblasts. In a cell migration screen for proteins containing PtdIns3P‐binding motifs, we identified the phosphoinositide 5‐kinase PIKfyve and the phosphoinositide 3‐phosphatase MTMR3, which together constitute a phosphoinositide loop that produces PtdIns5P via PtdIns(3,5)P2. The ability of PtdIns5P to stimulate cell migration was demonstrated directly with exogenous PtdIns5P and a PtdIns5P‐producing bacterial enzyme. Thus, the identified phosphoinositide loop defines a new role for PtdIns5P in cell migration. 相似文献
192.
Julio C. González-Olvera Eva González-Jasso Alejandra Rojas-Molina 《Nucleosides, nucleotides & nucleic acids》2013,32(9):642-655
AbstractDegradation of 2′-deoxyribonucleosides in 0.5?M aqueous pyrrolidine at 110?°C proceeds at different rates, ordered as deoxyuridine?>?deoxyadenosine?>?deoxycytidine?>?deoxyguanosine ??deoxythymidine. Deoxyadenosine degradation produces the free base, adenine, while deoxycytidine by deamination produces deoxyuridine, and then uracil. The solvolysis of deoxyadenosine has an activation energy of 23.3?kcal/mol. Ammonolysis is slower than pyrrolidinolysis for deoxyadenosine, but faster for deoxyguanosine. In pyrrolidinolysis of the trinucleotides, d-TGT and d-TAT, the guanine moiety reacts faster than the adenine moiety. These trends are interpreted in terms of the ionization of the guanine moieties under basic conditions, rendering them less susceptible to nucleophilic attack. 相似文献
193.
Rosario Vecchio Salvatore Marchese Francesco Ferla Linda Spataro Eva Intagliata 《Parasitology international》2013,62(6):487-493
BackgroundSolitary subcutaneous hydatid cyst is not frequent and the only symptom is generally a silent growing mass. Total excision remains the mainstay of treatment. Aim of the study was to present a case surgically treated and perform a statistical analysis reviewing previous published works in order to define a correct approach to diagnosis and treatment.Methods264 documents from Medline database were considered for primary subcutaneous hydatid cyst cases. Data concerning geographic region, gender, age, job, location, evolving time, history and physical, mobility, diameter, laboratory, imaging, locularity (uni- or multilocular cyst), fine-needle aspiration, preoperative diagnosis, neoadjuvant chemotherapy, treatment, spillage, adjuvant therapy, follow-up and recurrences were ordered in a database and analysed performing t-test, Fisher's test and Pearson's test.Results23 cases, included ours, resulted suitable for our study. Lower extremities were involved in most cases (60.9%) and the thigh represented the most common site (34.8%), whereas upper extremities were the rarest location (8.7%). Patients with head and neck located cysts were younger than those with upper extremities cysts (P = 0.037). Patients who underwent multiple imaging approach received a significantly correct first diagnosis (P = 0.001) and ultrasonography, unlike other techniques, appeared to be essential (P = 0.013).Case reportA 68-year-old man who lived and worked in his farm in Sicily (Italy) presented with a 30-year-growing mass in the deltoid region measuring 10 cm. Ultrasonography and magnetic resonance imaging strongly suggested hydatid cyst. Therefore the cyst was excised and pathology confirmed the diagnosis.ConclusionSolitary subcutaneous hydatid cyst must always be considered in the differential diagnosis of silent growing mass in soft tissues. History and physical associated with ultrasound and magnetic resonance imaging are sufficient to achieve a correct preoperative diagnosis. 相似文献
194.
195.
Richard A. Stabler Jonas T. Larsson Suaad Al‐Jaberi Eva M. Nielsen Emily Kay Clarence C. Tam Craig D. Higgins Laura C. Rodrigues Judith F. Richardson Sarah J. O'Brien Brendan W. Wren 《Environmental microbiology》2013,15(8):2371-2383
Campylobacter jejuni is the leading cause of human bacterial gastroenteritis worldwide, but source attribution of the organism is difficult. Previously, DNA microarrays were used to investigate isolate source, which suggested a non‐livestock source of infection. In this study we analysed the genome content of 162 clinical, livestock and water and wildlife (WW) associated isolates combined with the previous study. Isolates were grouped by genotypes into nine clusters (C1 to C9). Multilocus sequence typing (MLST) data demonstrated that livestock associated clonal complexes dominated clusters C1–C6. The majority of WW isolates were present in the C9 cluster. Analysis of previously reported genomic variable regions demonstrated that these regions were linked to specific clusters. Two novel variable regions were identified. A six gene multiplex PCR (mPCR) assay, designed to effectively differentiated strains into clusters, was validated with 30 isolates. A further five WW isolates were tested by mPCR and were assigned to the C7‐C9 group of clusters. The predictive mPCR test could be used to indicate if a clinical case has come from domesticated or WW sources. Our findings provide further evidence that WW C. jejuni subtypes show niche adaptation and may be important in causing human infection. 相似文献
196.
It has been hypothesized that a high reproductive output contributes to the unique gigantism in large dinosaur taxa. In order to infer more information on dinosaur reproduction, we established allometries between body mass and different reproductive traits (egg mass, clutch mass, annual clutch mass) for extant phylogenetic brackets (birds, crocodiles and tortoises) of extinct non-avian dinosaurs. Allometries were applied to nine non-avian dinosaur taxa (theropods, hadrosaurs, and sauropodomorphs) for which fossil estimates on relevant traits are currently available. We found that the reproductive traits of most dinosaurs conformed to similar-sized or scaled-up extant reptiles or birds. The reproductive traits of theropods, which are considered more bird-like, were indeed consistent with birds, while the traits of sauropodomorphs conformed better to reptiles. Reproductive traits of hadrosaurs corresponded to both reptiles and birds. Excluding
Massospondylus
carinatus
, all dinosaurs studied had an intermediary egg to body mass relationship to reptiles and birds. In contrast, dinosaur clutch masses fitted with either the masses predicted from allometries of birds (theropods) or to the masses of reptiles (all other taxa). Theropods studied had probably one clutch per year. For sauropodomorphs and hadrosaurs, more than one clutch per year was predicted. Contrary to current hypotheses, large dinosaurs did not have exceptionally high annual egg numbers (AEN). Independent of the extant model, the estimated dinosaur AEN did not exceed 850 eggs (75,000 kg sauropod) for any of the taxa studied. This estimated maximum is probably an overestimation due to unrealistic assumptions. According to most AEN estimations, the dinosaurs studied laid less than 200 eggs per year. Only some AEN estimates obtained for medium to large sized sauropods were higher (200-400 eggs). Our results provide new (testable) hypotheses, especially for reproductive traits that are insufficiently documented or lacking from the fossil record. This contributes to the understanding of their evolution. 相似文献
197.
Mahban Irandoust Julian Alvarez Zarate Isabelle Hubeek Ellen M. van Beek Karin Schornagel Aart J. F. Broekhuizen Mercan Akyuz Arjan A. van de Loosdrecht Ruud Delwel Peter J. Valk Edwin Sonneveld Pamela Kearns Ursula Creutzig Dirk Reinhardt Eveline S. J. M. de Bont Eva A. Coenen Marry M. van den Heuvel-Eibrink C. Michel Zwaan Gertjan J. L. Kaspers Jacqueline Cloos Timo K. van den Berg 《PloS one》2013,8(1)
Background
Recent studies show the importance of interactions between CD47 expressed on acute myeloid leukemia (AML) cells and the inhibitory immunoreceptor, signal regulatory protein-alpha (SIRPα) on macrophages. Although AML cells express SIRPα, its function has not been investigated in these cells. In this study we aimed to determine the role of the SIRPα in acute myeloid leukemia.Design and Methods
We analyzed the expression of SIRPα, both on mRNA and protein level in AML patients and we further investigated whether the expression of SIRPα on two low SIRPα expressing AML cell lines could be upregulated upon differentiation of the cells. We determined the effect of chimeric SIRPα expression on tumor cell growth and programmed cell death by its triggering with an agonistic antibody in these cells. Moreover, we examined the efficacy of agonistic antibody in combination with established antileukemic drugs.Results
By microarray analysis of an extensive cohort of primary AML samples, we demonstrated that SIRPα is differentially expressed in AML subgroups and its expression level is dependent on differentiation stage, with high levels in FAB M4/M5 AML and low levels in FAB M0–M3. Interestingly, AML patients with high SIRPα expression had a poor prognosis. Our results also showed that SIRPα is upregulated upon differentiation of NB4 and Kasumi cells. In addition, triggering of SIRPα with an agonistic antibody in the cells stably expressing chimeric SIRPα, led to inhibition of growth and induction of programmed cell death. Finally, the SIRPα-derived signaling synergized with the activity of established antileukemic drugs.Conclusions
Our data indicate that triggering of SIRPα has antileukemic effect and may function as a potential therapeutic target in AML. 相似文献198.
Eva C. Schulte Immanuel Stahl Darina Czamara Daniel C. Ellwanger Sebastian Eck Elisabeth Graf Brit Mollenhauer Alexander Zimprich Peter Lichtner Dietrich Haubenberger Walter Pirker Thomas Brücke Benjamin Bereznai Maria J. Molnar Annette Peters Christian Gieger Bertram Müller-Myhsok Claudia Trenkwalder Juliane Winkelmann 《PloS one》2013,8(11)
Approximately 20% of individuals with Parkinson’s disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance. 相似文献
199.
Carola E. Bunse Sylvia Borchers Pavankumar R. Varanasi Sabine Tischer Constan?a Figueiredo Stephan Immenschuh Ulrich Kalinke Ulrike K?hl Lilia Goudeva Britta Maecker-Kolhoff Arnold Ganser Rainer Blasczyk Eva M. Weissinger Britta Eiz-Vesper 《PloS one》2013,8(12)
Adoptive transfer of antiviral T cells enhances immune reconstitution and decreases infectious complications after stem cell transplantation. Information on number and function of antiviral T cells in stem cell grafts is scarce. We investigated (1) immunomodulatory effects of G-CSF on antiviral T cells, (2) the influence of apheresis, and (3) the optimal time point to collect antiviral cells.CMV-, EBV- and ADV-specific T cells were enumerated in 170 G-CSF-mobilized stem cell and 24 non-mobilized platelet donors using 14 HLA-matched multimers. T-cell function was evaluated by IFN-γ ELISpot and granzyme B secretion. Immunophenotyping was performed by multicolor flow cytometry.G-CSF treatment did not significantly influence frequency of antiviral T cells nor their in vitro expansion rate upon antigen restimulation. However, T-cell function was significantly impaired, as expressed by a mean reduction in secretion of IFN-γ (75% in vivo, 40% in vitro) and granzyme B (32% target-independent, 76% target-dependent) as well as CD107a expression (27%). Clinical follow up data indicate that the first CMV-reactivation in patients and with it the need for T-cell transfer occurs while the donor is still under the influence of G-CSF.To overcome these limitations, T-cell banking before mobilization or recruitment of third party donors might be an option to optimize T-cell production. 相似文献
200.
Min Xia Daxin Chen Valeria Endresz Ildiko Faludi Andrea Szabo Eva Gonczol Vijay Kakkar Xinjie Lu 《PloS one》2013,8(12)