Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the ...transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recently introduced 320-detector row CT enables whole brain perfusion imaging compared to a limited scanning area in 64-detector row CT. Our aim was to evaluate patient radiation exposure in ...comprehensive stroke imaging by using multidetector row CT consisting of standard CT of the head, CTA of cerebral and cervical vessels, and CTP.
Organ doses were measured by using LiF-TLDs located at several organ sites in an Alderson-Rando phantom. Effective doses were derived from these measurements. Stroke protocols including noncontrast head CT, CTA of cerebral and cervical vessels, and CTP were performed on 320- and 64-detector row scanners.
Measured effective doses for the different scanning protocols ranged between 1.61 and 4.56 mSv, resulting in an effective dose for complete stroke imaging of 7.52/7.54 mSv (m/f) for 64-detector row CT and 10.56/10.6 mSv (m/f) for 320-detector row CT. The highest organ doses within the area of the primary beam were measured in the skin (92 mGy) and cerebral hemispheres (69.91 mGy). Use of an eye-protection device resulted in a 54% decrease of the lens dose measured for the combo protocol for whole-brain perfusion with the 320-detector row CT scanner.
Phantom measurements indicate that comprehensive stroke imaging with multidetector row CT may result in effective radiation doses from 7.52 mSv (64-detector row CT) to 10.6 mSv (320-detector row CT). The technique of 320-detector row CT offers additional information on the time course of vascular enhancement and whole-brain perfusion. Physicians should weigh the potential of the new technique against the higher radiation dose that is needed. Critical doses that would cause organ damage were not reached.
E-mental health (eMH) encompasses the use of digital technologies to deliver, support, or enhance mental health services. Despite the growing evidence for the effectiveness of eMH interventions, the ...process of implementation of eMH solutions in healthcare remains slow throughout Europe. To address this issue, the e-Mental Health Innovation and Transnational Implementation Platform North-West Europe (eMEN) project was initiated to increase the dissemination and quality of eMH services in Europe. In this project, status analyses regarding eMH in the six participating countries (i.e., Belgium, France, Germany, Ireland, The Netherlands, and the UK) were conducted and eight recommendations for eMH were developed. Expert teams from the six participating countries conducted status analyses regarding the uptake of eMH based on a narrative literature review and stakeholder interviews. Based on these status analyses, the eMEN consortium developed eight policy recommendations to further support the implementation of eMH in Europe. The status analyses showed that the participating countries are in different stages of implementing eMH into mental healthcare. Some barriers to implementing eMH were common among countries (e.g., a limited legal and regulatory framework), while others were country-specific (e.g., fragmented, federal policies). The policy recommendations included fostering awareness, creating strong political commitment, and setting reliable standards related to ethics and data security. The eMEN project has provided the initial recommendations to guide political and regulatory processes regarding eMH. Further research is needed to establish well-tailored implementation strategies and to assess the generalizability of the recommendations beyond the countries involved in the eMEN project.
Information on physiological rates and tolerances helps one gain a cause-and-effect understanding of the role that some environmental (bottom–up) factors play in regulating the seasonality and ...productivity of key species. We combined the results of laboratory experiments on reproductive success and field time series data on adult abundance to explore factors controlling the seasonality of
Acartia
spp.,
Eurytemora affinis
and
Temora longicornis
, key copepods of brackish, coastal and temperate environments. Patterns in laboratory and field data were discussed using a metabolic framework that included the effects of ‘controlling’, ‘masking’ and ‘directive’ environmental factors. Over a 5-year period, changes in adult abundance within two south-west Baltic field sites (Kiel Fjord
Pier
, 54°19′89N, 10°09′06E, 12–21 psu, and North/Baltic Sea Canal
NOK
, 54°20′45N, 9°57′02E, 4–10 psu) were evaluated with respect to changes in temperature, salinity, day length and chlorophyll a concentration.
Acartia
spp. dominated the copepod assemblage at both sites (up to 16,764 and 21,771 females m
−3
at
NOK
and
Pier
) and was 4 to 10 times more abundant than
E. affinis
(to 2,939 m
−3
at
NOK
) and
T. longicornis
(to 1,959 m
−3
at
Pier
), respectively. Species-specific salinity tolerance explains differences in adult abundance between sampling sites whereas phenological differences among species are best explained by the influence of species-specific thermal windows and prey requirements supporting survival and egg production. Multiple intrinsic and extrinsic (environmental) factors influence the production of different egg types (normal and resting), regulate life-history strategies and influence match–mismatch dynamics.
Fluorescence resonance energy transfer (FRET) provides information on the distance between a donor and an acceptor dye in the range 10 to 100 Å. Knowledge of the exact positions of some dyes with ...respect to nucleic acids now enables us to translate these data into precise structural information using molecular modeling. Advances in the preparation of dye-labeled nucleic acid molecules and in new techniques, such as the measurement of FRET in polyacrylamide gels or
in vivo, will lead to an increasingly important role of FRET in structural and molecular biology.
The aim of this study was to report initial clinical experience with a 320-slice CT scanner and to perform an image quality evaluation. 26 patients with presumptive cerebrovascular pathology ...underwent 320-slice CT. Single-rotation CT of the head, incremental CT angiography (three-dimensional (3D) CTA) as well as four-dimensional whole-brain CTA (4D CTA) and whole-brain CT perfusion (CTP) were performed and the resulting images were assessed for quality and compared with those obtained with 64-slice CT protocols. 320-slice CT neuroimaging could be performed in all cases. The image quality of 320-slice CT of the head and 3D CTA was inferior to that of the 64-slice protocols. The image quality of 4D 320-slice CTA was rated as inferior to both 320- and 64-slice 3D CTA. 4D CTA-CTP imaging added information with pivotal clinical implications. 320-slice CT neuroimaging is feasible technique that permits whole-brain 4D imaging and has the potential to identify pathologies with altered haemodynamics. However, image quality is a limitation of this technique at present.
Pelizaeus-Merzbacher-like disease (PMLD) is a genetically heterogeneous disorder within the group of hypomyelinating leukoencephalopathies. Mutations of the gap junction protein alpha 12 (GJA12) gene ...are known to cause one autosomal recessive PMLD form. Few patients with GJA12 mutated PMLD have been reported, and to date, the frequency as well as the genotypic and phenotypic spectrum of GJA12 related PMLD is unclear.
We report mutation analysis of the GJA12 gene in a clinical and radiologic well-characterized multiethnic cohort of 193 patients with PMLD from 182 families.
Only 16 patients (8.3%) from 14 families (7.7%) carry GJA12 mutations including five families where we detected only one mutated allele. Among those, we identified 11 novel alterations. Thus, GJA12 mutations are a rather rare cause for Pelizaeus-Merzbacher-like disease. The clinical phenotype of patients with a GJA12 mutation was evaluated and is overall comparable to the clinical features seen in mild forms of proteolipid protein 1 (PLP1) related disorder but with better cognition and earlier signs of axonal degeneration.
The vertebrate kinetochore complex assembles at the centromere on α-satellite DNA. In humans, α-satellite DNA has a repeat length of 171 bp slightly longer than the DNA in the chromatosome containing ...the linker histone H1. The centromere-binding protein CENP-B binds specifically to α-satellite DNA with properties of a centromeric-linker histone. Here, we analysed if linker histone H1 is present at or excluded from centromeric chromatin by CENP-B. By immunostaining we detected the presence, but no enrichment or depletion of five different H1 subtypes at centromeric chromatin. The binding dynamics of H1 at centromeric sites were similar to that at other locations in the genome. These dynamics did not change in CENP-B depleted cells, suggesting that CENP-B and H1 co-exist in centromeric chromatin with no or little functional overlap. By bimolecular fluorescence complementation (BiFC) and Förster resonance energy transfer (FRET), we revealed that the linker histone H1 subtypes H1° and H1.2 bind to centromeric chromatin in interphase nuclei in direct neighbourhood to inner kinetochore proteins.
The Escherichia coli low-copy-number plasmid R1 contains a segregation machinery composed of parC, ParR and parM. The R1 centromere-like site parC contains two separate sets of repeats. By atomic ...force microscopy (AFM) we show here that ParR molecules bind to each of the 5-fold repeated iterons separately with the intervening sequence unbound by ParR. The two ParR protein complexes on parC do not complex with each other. ParR binds with a stoichiometry of about one ParR dimer per each single iteron. The measured DNA fragment lengths agreed with B-form DNA and each of the two parC 5-fold interon DNA stretches adopts a linear path in its complex with ParR. However, the overall parC/ParR complex with both iteron repeats bound by ParR forms an overall U-shaped structure: the DNA folds back on itself nearly completely, including an angle of ∼150°. Analysing linear DNA fragments, we never observed dimerized ParR complexes on one parC DNA molecule (intramolecular) nor a dimerization between ParR complexes bound to two different parC DNA molecules (intermolecular). This bacterial segrosome is compared to other bacterial segregation complexes. We speculate that partition complexes might have a similar overall structural organization and, at least in part, common functional properties.
Abstract
Purpose:
To evaluate the additional benefit of true geometric (air-gap) magnification views for the characterization of microcalcifications in digital mammography.
Materials and Methods:
...After ethical approval, we retrospectively reviewed patient records to identify 100 patients with suspicious microcalcifications (35 malignant, 65 benign) who had a standard digital mammography and an additional digital magnification view in the same projection within three months. All images were obtained using an amorphous silicon-based full-field digital system (Senographe 2000 D, GE Healthcare, Chalfont St. Giles, UK). Images were independently analyzed by six board-certified radiologists. The probability of malignancy was estimated using first standard contact mammography alone (MG) and then mammography in combination with the magnification view (MG+MAG) using a modified Breast Imaging Reporting and Data System (BI-RADS) classification system and a percentage scale. Results were compared using receiver operating characteristic (ROC) analysis. In addition, readers assessed the subjective visibility of the calcifications.
Results:
For all six readers combined, the area under the curve (AUC) was 0.664 ± 0.052 for MG and 0.813 ± 0.042 for MG + MAG, resulting in a statistically significant improvement of 0.148 ± 0.120. Each reader had a higher AUC for MG + MAG than MG, with the improvement being statistically significant in four of the six readers. In 76.34 % of the cases, MG + MAG resulted in better visibility of calcifications compared with mammography alone. In 33 % slightly more and in 39 % significantly more calcifications were found.
Conclusion:
Even in digital mammography with the option of using electronic magnification (zoom) at the viewing workstation, true geometric (air-gap) magnification views remain important for the visibility and correct classification of microcalcifications and for the assessment of their extent.
Citation Format:
• Fallenberg EM, Dimitrijevic L, Diekmann F et al. Impact of Magnification Views on the Characterization of Microcalcifications in Digital Mammography. Fortschr Röntgenstr 2014; 186: 274 – 280
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