A detailed inventory of DNA copy number alterations in four commonly used Hodgkin's lymphoma cell lines

Background and Objectives Classical Hodgkin's lymphoma (cHL) is a common malignant lymphoma characterized by the presence of large, usually multinucleated malignant Hodgkin and Reed Sternberg (HRS) cells which are thought to be derived from germinal center B-cells. In cHL, the HRS cells constitute less than 1% of the tumor volume; consequently the profile of genetic aberrations in cHL is still poorly understood. Design and Methods In this study, we subjected four commonly used cHL cell lines to array comparative genomic hybridization (aCGH) in order to delineate known chromosomal aberrations in more detail and to search for small hitherto undetected genomic imbalances. Results The aCGH profiles of the four cell lines tested confirmed the complex patterns of rearrangements previously demonstrated with multicolor fluorescence in situ hybridization and chromosomal CGH (cCGH). Importantly, aCGH allowed a much more accurate delineation of imbalances as compared to previous studies performed at a chromosomal level of resolution. Furthermore, we detected 35 hitherto undetected aberrations including a homozygous deletion of chromosomal region 15q26.2 in the cell line HDLM2 encompasing RGMA and CHD2 and an amplification of the STAT6 gene in cell line L1236 leading to STAT6 overexpression. Finally, in cell line KM-H2 we found a 2.35 Mb deletion at 16q12.1 putatively defining a small critical region for the recurrent 16q deletion in cHL. This region contains the CYLD gene, a known suppressor gene of the NF-kappa B pathway. Interpretation and Conclusions aCGH was performed on four cHL cell lines leading to the improved delineation of known chromosomal imbalances and the detection of 35 hitherto undetected aberrations. More specifically, our results highlight STAT6 as a potential transcriptional target and identified RGMA, CHD2 and CYLD as candidate tumor suppressors in cHL

Ink-jet printed BaTiO₃ for photonics

ABSTRACTA water-based BaTiO3 precursor solution, suited for ink-jet printing of hetero-epitaxial BaTiO3 layers on LaAlO3 single-crystal substrates was developed. First, a study on the simultaneous stabilization of Ba2+ and Ti4+ions in a neutral, aqueous environment was performed. Thermal analysis of the precursor was used to select appropriate temperature programs and the rheology of the solutions is studied to optimize dipcoating and later ink-jet printing parameters. On both substrates, it was possible to obtain epitaxial layers of about 200 nm thickness after sintering at temperatures above 1000 °C. Currently, we are adapting the thermal program and heating atmosphere in order to reduce the sintering temperatures, decrease the surface roughness and increase density.</jats:p

Is MS Intention Tremor Amplitude Related to Changed Peripheral Reflexes?

Intention tremor is related to lesions in the cerebellum or connected pathways. Intention tremor amplitude decreased after peripheral arm cooling in patients with multiple sclerosis (MS), likely caused by a reduction of muscle spindle afferent inflow, while amplitude increased when muscle spindles were artificially stimulated by tendon vibration. This study investigated the contribution of peripheral reflexes to the generation of MS intention tremor. Tendon reflexes of biceps, triceps, and brachioradialis, muscles were measured, using an electromechanical triggered reflex hammer. MS patients with (n = 17) and without (n = 17) upper limb intention and 18 healthy controls were tested. Latency of brachioradialis, biceps, and triceps tendon reflexes was greater in MS patients with tremor than in healthy controls and MS patients without tremor (except for the triceps reflex). Peak and peak-to-peak amplitude were not different between groups. It is concluded that tendon reflexes were delayed but not enlarged in MS patients with tremor

Altered expression of maize PLASTOCHRON1 enhances biomass and seed yield by extending cell division duration

Maize is the highest yielding cereal crop grown worldwide for grain or silage. Here, we show that modulating the expression of the maize PLASTOCHRON1 (ZmPLA1) gene, encoding a cytochrome P450 (CYP78A1), results in increased organ growth, seedling vigour, stover biomass and seed yield. The engineered trait is robust as it improves yield in an inbred as well as in a panel of hybrids, at several locations and over multiple seasons in the field. Transcriptome studies, hormone measurements and the expression of the auxin responsive DR5(rev): mRFPer marker suggest that PLA1 may function through an increase in auxin. Detailed analysis of growth over time demonstrates that PLA1 stimulates the duration of leaf elongation by maintaining dividing cells in a proliferative, undifferentiated state for a longer period of time. The prolonged duration of growth also compensates for growth rate reduction caused by abiotic stresses

High-throughput stem-loop RT-qPCR miRNA expression profiling using minute amounts of input RNA

MicroRNAs (miRNAs) are an emerging class of small non-coding RNAs implicated in a wide variety of cellular processes. Research in this field is accelerating, and the growing number of miRNAs emphasizes the need for high-throughput and sensitive detection methods. Here we present the successful evaluation of the Megaplex reverse transcription format of the stem-loop primer-based real-time quantitative polymerase chain reaction (RT-qPCR) approach to quantify miRNA expression. The Megaplex reaction provides simultaneous reverse transcription of 450 mature miRNAs, ensuring high-throughput detection. Further, the introduction of a complementary DNA pre-amplification step significantly reduces the amount of input RNA needed, even down to single-cell level. To evaluate possible pre-amplification bias, we compared the expression of 384 miRNAs in three different cancer cell lines with Megaplex RT, with or without an additional pre-amplification step. The normalized Cq values of all three sample pairs showed a good correlation with maintenance of differential miRNA expression between the cell lines. Moreover, pre-amplification using 10 ng of input RNA enabled the detection of miRNAs that were undetectable when using Megaplex alone with 400 ng of input RNA. The high specificity of RT-qPCR together with a superior sensitivity makes this approach the method of choice for high-throughput miRNA expression profiling

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Politionele integriteit onderzocht

In dit hoofdstuk definiëren we het begrip ‘politionele integriteit’ en staan we stil bij mogelijke morele dilemma’s die politieambtenaren kunnen ervaren en het bestaan van een zogenaamde politiecultuur. We gaan ook dieper in op de vorm die een integriteitsbeleid kan aannemen en de instrumenten die daarbij nuttig kunnen zijn. Er wordt een typologie van politionele integriteitsschendingen gegeven en er wordt ingegaan op integriteitsonderzoeken

Integrating serious games and tangible objects for functional handgrip training: A user study of Handly in persons with Multiple Sclerosis

We present Handly, an integrated upper-limb rehabilitation system for persons with a neurological disorder. Handly consists of tangibles for training four hand tasks with specific functional handgrips and a motivational game. These persons need intensive personalized therapy in order to sustain or enhance their abilities and aptitude in daily activities. Conventional approaches require intense support by a therapist or usage of expensive robots, both of which are not a sustainable model of training. Handly combines tangibles specifically designed for repetitive task-oriented motor skill training of typical daily activities with serious gaming, thus offering a comprehensive approach. A feedback mechanism guides the user and an accessible game environment stimulates individual training. We performed an initial evaluation of Handly with eight persons with Multiple Sclerosis. We show that a tangible-virtual environment for intensive upper-limb rehabilitation is feasible and that this approach is highly appreciated by the patients

Accuracy of self-evaluation in persons with multiple sclerosis

Multiple Sclerosis (MS) is a chronic illness of the central nervous system causing different symptoms that affect important skills in the driving task. The condition is progressive, so that there is a point in time in which the patient is no longer capable of safe driving. The purpose of the study was to assess whether persons with MS can evaluate their own driving skills accurately. 20 persons with MS (mean age 49 ±9) and 17 healthy controls (mean age 41 ±16) from 22 to 62 years old took part in the experiment. The male-female ratio (40%-60%) was equal in both groups. All participants drive a normal car with a gear shift (without adjustments) regularly. The results of a subjective measure of driving skills (questionnaire) were compared to an objective measure (driving simulator test). The driving test consisted of three separate trajectories assessing skills that may be affected by visual, cognitive and physical limitations. The questionnaire contained the same items. Results of the questionnaire indicate that persons with MS acknowledge that they have problems while driving, which are caused by MS, but they do not think these have a significant effect on their driving abilities. They rate their own abilities even higher than the healthy control group does on questions such as “how much difficulty do you have with overtaking?”. In contrast, their self-evaluation is relatively pessimistic in questions about divided attention. The simulator driving test revealed that persons with MS perform worse than healthy controls, especially on a secondary task and when having to overtake other vehicles. When subjective and objective measures of driving skills are compared, persons with MS overestimate themselves more than the healthy control group. The overestimation is significant but does not necessarily indicate a problem of unsafety in traffic. The overestimations are more prominent when judging traffic flow, operationalized by overtaking manoeuvres, and to a lesser extent concerning divided attention. The group is more accurate in assessing their physical abilities, but their performances are also the best in this domain