The chloroplast proteome comprises nuclear- and plastome-encoded proteins. In order to function correctly these proteins must be transported, either cotranslationally or posttranslationally, to their ...final destination in the chloroplast. Here the chloroplast signal recognition particle (cpSRP) which is present in two different stromal pools plays an essential role. On the one hand, the conserved 54
kDa subunit (cpSRP54) is associated with 70S ribosomes to function in the cotranslational transport of the plastid-encoded thylakoid membrane protein D1. On the other hand, the cpSRP consists of cpSRP54 and a unique 43
kDa subunit (cpSRP43) and facilitates the transport of nuclear-encoded light-harvesting chlorophyll-binding proteins (LHCPs), the most abundant membrane proteins of the thylakoids. In addition to cpSRP, the cpSRP receptor cpFtsY and the thylakoid membrane protein Alb3 are required for posttranslational LHCP integration in a GTP-dependent manner. In contrast to the universally conserved cytosolic SRP, the chloroplast SRP of higher plants lacks an SRP-RNA component. Interestingly, cpSRP-RNA genes have been identified in the plastome of lower plants, indicating that their cpSRP structure resembles the cytosolic SRP.
Despite a relatively low fatality rate, the 2009 H1N1 pandemic virus differed from other seasonal viruses in that it caused mortality and severe pneumonia in the young and middle-aged population ...(18-59 years old). The mechanisms underlying this increased disease severity are still poorly understood. In this study, a human isolate of the 2009 H1N1 pandemic virus was adapted to the mouse (MAp2009). The pathogenicity of the MAp2009 virus and the host immune responses were evaluated in the mouse model and compared to the laboratory H1N1 strain A/Puerto Rico/8/1934 (PR8). The MAp2009 virus reached consistently higher titers in the lungs over 14 days compared to the PR8 virus, and caused severe disease associated with high morbidity and 85% mortality rate, contrasting with the 0% death rate in the PR8 group. During the early phase of infection, both viruses induced similar pathology in the lungs. However, MAp2009-induced lung inflammation was sustained until the end of the study (day 14), while there was no sign of inflammation in the PR8-infected group by day 10. Furthermore, at day 3 post-infection, MAp2009 induced up to 10- to 40-fold more cytokine and chemokine gene expression, respectively. More importantly, the numbers of CD4+ T cells and virus-specific CD8+ T cells were significantly lower in the lungs of MAp2009-infected mice compared to PR8-infected mice. Interestingly, there was no difference in the number of dendritic cells in the lung and in the draining lymph node. Moreover, mice infected with PR8 or MAp2009 had similar numbers of CCR5 and CXCR3-expressing T cells, suggesting that the impaired T cell response was not due to a lack of chemokine responsiveness or priming of T cells. This study demonstrates that a mouse-adapted virus from an isolate of the 2009 pandemic virus interferes with the adaptive immune response leading to a more severe disease.
Abstract
The article proposes a technical solution for a multi-frequency meter of electrical impedance parameters based on a precision impedance converter AD5933 from analog devices. The technical ...solution can be used in the development of portable devices for the diagnosis of biological objects.
Background and Objective
Nutrition and body weight are modifying factors for periodontitis. The purpose of this study was to quantify two molecules (ghrelin and chemerin), released in association ...with food intake and obesity, in periodontally healthy and diseased individuals with respect to different body mass categories.
Material and Methods
The two main groups (patients with chronic periodontitis and periodontally healthy/gingivitis volunteers) were subdivided into groups of subjects with normal weight body mass index (BMI) <25 and groups of overweight/obese subjects (BMI ≥25). Subgingival bacteria were analysed and the levels of acylated and total ghrelin, chemerin and interleukin‐1β (IL‐1β) were assessed in saliva, gingival crevicular fluid and serum.
Results
The amount of Treponema denticola present subgingivally was significantly higher in the groups of patients with chronic periodontitis as well as in periodontally healthy/gingivitis individuals with BMI ≥25 than in periodontally healthy/gingivitis individuals with BMI <25. The amount of total ghrelin in gingival crevicular fluid differed significantly between the groups, with the lowest levels found in the group of patients with chronic periodontitis and BMI ≥25. The levels of chemerin in gingival crevicular fluid were significantly higher in each chronic periodontitis group than in periodontally healthy/gingivitis individuals with BMI <25. However, the level of IL‐1β in the gingival crevicular fluid was most differentiating between the groups, with the highest levels found in the group of patients with chronic periodontitis and BMI <25 and the lowest levels in periodontally healthy/gingivitis individuals with BMI <25. No significant differences between any groups were seen for chemerin or for acylated ghrelin in the stimulated whole saliva, or for acylated and total ghrelin in peripheral blood serum. The BMI correlated with the serum level of chemerin.
Conclusion
Low ghrelin and high chemerin levels in the gingival crevicular fluid might be linked to periodontal disease and overweight/obesity. However, unlike IL‐1β, the levels of chemerin and ghrelin in gingival crevicular fluid are not reliable indicators of periodontal destruction.
The resistance of glioblastoma to existing therapies puts limits on
quality-of-life improvements and patient survival with a glioblastoma
diagnosis. The development of new effective glioblastoma ...therapies is based on
knowledge about the mechanisms governing tumor resistance to therapeutic
agents. Virotherapy is one of the most actively developing approaches to the
treatment of malignant neoplasms: glioblastoma in particular. Previously, we
demonstrated that the recombinant vaccinia virus VV-GMCSF-Lact exhibits
in vitro
cytotoxic activity and
in vivo
antitumor efficacy against human glioblastoma. However, the studied
glioblastoma cell cultures had different sensitivities to the oncotoxic effect
of the virus. In this study, we investigated cancer stem cell (CSC) surface
markers in glioblastoma cells with different sensitivities to VV-GMCSFLact
using flow cytometry and we assessed the levels of proteins affecting viral
entry into cells and virus infection efficiency by western blotting. We showed
that cell cultures more sensitive to VV-GMCSF-Lact are characterized by a
greater number of cells with CSC markers and a lower level of activated Akt
kinase. Akt probably inhibits lactaptin-induced apoptosis in virus-resistant
cells. Hence, we suggest that the sensitivity of glioblastoma cells to the
oncotoxic effect of VV-GMCSF-Lact is determined by the nature and extent of the
disturbances in cell death regulation in various cultures. Further
investigation of the factors affecting glioblastoma resistance to virotherapy
will test this hypothesis and identify targets for antitumor therapy, combined
with VV-GMCSF-Lact.
Grain growth inhibition in ultrafine hardmetals Pötschke, J.; Richter, V.; Gestrich, T. ...
International journal of refractory metals & hard materials,
08/2017, Letnik:
66
Journal Article
Recenzirano
Ultrafine and nanoscaled hardmetals show mechanical properties like hardness and bending strength which lie way above conventional fine or submicron grained hardmetals. To achieve such fine ...microstructures very fine WC starting powders as well as grain growth inhibitors such as Cr3C2 or VC are needed. To study the grain growth inhibition in ultrafine hardmetals investigations on samples made from nearly nanoscaled WC and Co starting powders with and without the addition of Cr3C2 were done. For studying the dissolution behaviour of Cr3C2 and the evolution of density, magnetic properties and lattice parameters of WC during sintering, interrupted sintering experiments were carried out. Thermal analysis techniques including TG-MS and DSC were used, to link the observed changes to expected reactions. The results show that grain growth inhibitors greatly influence the sintering behaviour already way below the eutectic melting of WC-Co. Especially dissolution of Cr3C2 and homogenous distribution of Cr within the samples already starts below 800 °C with the reduction of W surface oxides and the creation and spreading of Cr oxides. The findings are relevant for optimising sintering regime, composition (amount of grain growth inhibitors) as well as the microstructure and mechanical properties.
The epidermal growth factor receptor (EGFR) is an oncogenic tyrosine kinase that is involved in tumor initiation and progression, making EGFR inhibitors and monoclonal antibodies to this receptor ...essential for anti-tumor therapy. We have previously shown that EGFR transgene expression in the human breast adenocarcinoma cell line MCF7 (MCF7-EGFR) stimulates the 3D spheroid-like growth. The primary focus of our present work was to investigate whether EGFR inhibition could affect the assembly of spheroids or lead to the destruction of pre-existing spheroids. We compared the effects of anti-EGFR siRNA, the anti-EGFR monoclonal antibody cetuximab, and the tyrosine kinase inhibitor AG1478 on dissociated and spheroid MCF7-EGFR cells. MCF7-EGFR cells were found to have a 2.5-fold higher sensitivity towards the cytotoxic effects of cetuximab and AG1478 compared with the parental MCF7 cell line. The suppression of EGFR mRNA with siRNA was found to reduce the sphere formation, whereas treating the pre-existing spheroids had no such effect. Treatment of dissociated spheroids with cetuximab and AG1478 was also found to inhibit the MCF7-EGFR sphere formation. We suggest that EGFR expression is important, at least, during the spheroid formation stage. The transition of a MCF7wt adherent cell culture to MCF7-EGFR spheroids was accompanied by a considerable increase in N-cadherin adhesion proteins. The level of N-cadherin decreased when MCF7-EGFR cells were treated with siRNA and cetuximab. Thus, we have demonstrated that N-cadherin is involved in the EGFR-dependent formation of MCF7-EGFR spheroids. Accordingly, MCF7-EGFR spheroids can be considered a suitable model for studying aggressive hormone-positive breast tumors.
Animal migrations offer a unique opportunity for developing and testing hypotheses about the ecological requirements of different species and the tradeoffs that they make between conflicting ...life‐history demands. There has been relatively little research into the causes and consequences of migrations by fruit bats, despite their potential significance for pollination and seed dispersal. We assessed the causes of one of the most spectacular migrations of fruit bats known: the annual influx of an estimated 5–10 million E. helvum into Kasanka National Park in Zambia. We tested several predictions based on the hypothesis that E. helvum migrates to exploit seasonal variations in food supply opportunistically. Phenological data, feeding observations and monitoring of fruit bat movements provided the first quantitative evidence in support of the hypothesis that the migration of E. helvum in Zambia is driven by food supply. The E. helvum colony exhibited several surprising behaviors, including a tendency for migratory satellite colonies to aggregate, rather than to disperse, during the time of peak food production, and a tendency to fly well beyond the most immediate food sources when foraging. Alternative hypotheses to explain the E. helvum migration were not supported, but further research is needed to clarify the results of this preliminary study. Both the size of the colony and its potential for large‐scale movements suggest that this bat may play an important economic and ecological role over a significant portion of sub‐Saharan Africa. Information is still lacking about migration routes, food sources, habitat requirements and the role of migration in disease transmission between colonies of E. helvum.
Patients with multiple stenoses or occlusions of the extracranial arteries require an individualized diagnostic approach. We evaluated the feasibility and clinical utility of a novel MR imaging ...technique for regional perfusion imaging in this patient group.
Superselective pseudocontinuous arterial spin-labeling with a circular labeling spot enabling selective vessel labeling was added to routine imaging in a prospective pilot study in 50 patients (10 women, 70.05 ± 10.55 years of age) with extracranial steno-occlusive disease. Thirty-three had infarct lesions. DSC-MR imaging was performed in 16/50 (32%), and cerebral DSA, in 12/50 patients (24%). Vascular anatomy and the distribution of vessel stenoses and occlusions were defined on sonography and TOF-MRA. Stenoses were classified according to the NASCET criteria. Infarct lesions and perfusion deficits were defined on FLAIR and DSC-MR imaging, respectively. Individual perfusion patterns were defined on the superselective pseudocontinuous arterial spin-labeling maps and were correlated with vascular anatomy and infarct lesion localization.
The superselective pseudocontinuous arterial spin-labeling imaging sequence could be readily applied by trained technicians, and the additional scan time of 12.7 minutes was well-tolerated by patients. The detected vessel occlusions/stenoses and perfusion patterns corresponded between cerebral DSA and superselective pseudocontinuous arterial spin-labeling maps in all cases. Perfusion deficits on DSC-CBF maps significantly correlated with those on superselective pseudocontinuous arterial spin-labeling maps (Pearson
= 0.9593,
< .01). Individual collateral recruitment patterns were not predictable from the vascular anatomy in 71% of our patients.
Superselective pseudocontinuous arterial spin-labeling is a robust technique for regional brain perfusion imaging, suitable for the noninvasive diagnostics of individual perfusion patterns in patients with complex cerebrovascular disease.
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