The analysis of injection molding defects caused by gate vestiges

Issues of product safety are the most serious problems of an injection molded product due to their risk to human health. Such a safety problem can be the needle-shaped vestige at the gate zone of injection molded products, called a gate vestige. Only observations of the formation of gate vestiges can be found in the literature, but the processing parameters influencing their dimensions, especially their height have not been studied yet. Our goal was to study the effect of various injection molding processing parameters and gate constructions on gate vestige formation

NFKB1 -94ins/delATTG polymorphism is a novel prognostic marker in first line-treated multiple myeloma

Nuclear factor kappa B (NFKB) plays an important role in multiple myeloma (MM), and bortezomib affects this pathway. We retrospectively analysed the effect of the NFKB1 -94ins/delATTG polymorphism on the survival of 295 MM patients treated at a single centre. The median progression-free survival (PFS) was 790 (659-921) d in patients with NFKB1 homozygous insertion genotype (I/I, n = 99) and 624 (515-733) d in deletion-carriers (I/D&D/D, n = 196, P = 0.013). In multivariate analysis, I/I carriers showed a favourable PFS compared to I/D&D/D with a hazard ratio of 0.622 (0.457-0.847), P = 0.003, in addition to international staging system (ISS) score, fluorescence in situ hybridization (FISH) risk score, age and bortezomib treatment. I/I patients benefited more from bortezomib treatment [PFS 902 (703-1101) and 580 (343-817), P = 0.008] than I/D&D/D patients [PFS 659 (487-831) and 488 (323-653), P = 0.531]; in addition the beneficial effect of low ISS score was not observed in the I/D&D/D group [PFS 639 (454-824) and 650 (458-842), P = 0.226], while it was clear in I/I patients [PFS 1140 (803-1477) and 580 (408-752), P < 0.001]. We conclude that homozygous carriers of the insertion allele of the NFKB1 -94ins/delATTG polymorphism have a better prognosis and probably benefit more from bortezomib treatment than MM patients carrying the deletion allele

Greenhouse bumblebees (Bombus terrestris) spread their genes into the wild

Bumblebees (Bombus spp.) are commonly used for greenhouse pollination of tomatoes and other crop plants. The colonies used for this purpose are provided by commercial bumblebee breeders, which by now operate at a professional company level. As a result of this practice commercially bred bumblebee colonies are transported and used over large distances and national borders, introducing subspecies into non-endemic regions. The question whether and to what extends gene flow between such managed greenhouse and wild bumblebee populations exists, so far has not been addressed. Here we used samples from three greenhouses in Poland and the surrounding populations to address this question. Using microsatellite DNA data we found strong genetic introgression from the sampled greenhouse populations into the adjacent populations. Depending on the analysed population, the number of individuals assigned to the greenhouse populations ranged from 0.08 to 0.47. We also found that more distant populations were much less affected by genetic introgression from the greenhouses

Extraction methods for phycocyanin determination in freshwater filamentous cyanobacteria and their application in a shallow lake

Phycocyanin (PC) is one of the water-soluble accessory pigments of cyanobacteria species, and its concentration in aquatic systems is used to estimate the presence and relative abundance of blue-green algae. PC concentration and the PC/Chl-a ratio of four N2-fixing filamentous cyanobacteria strains (Cylindrospermopsis raciborskii, Anabaena spiroides, Aphanizomenon flos-aquae and Aphanizomenon issatschenkoi) common to Lake Balaton (Hungary) were determined using repeated freezing and thawing. A strong linear correlation was found between the extracted PC and Chl-a concentrations for all strains at high Chl-a concentrations (almost stable PC/Chl-a ratio in the range of 20−100 µg l−1 Chl-a). Extraction of PC and Chl-a from samples with low biomass of cyanobacteria (less than 20 µg l−1 Chl-a) proved to be unreliable using the standard protocol of freeze–thaw cycles (coefficients of variation exceeding 10–15%). In order to find an extraction method that is robust in fresh waters characterized by low algae biomass (e.g. Lake Balaton), the effectiveness of four extraction methods (repeated freeze–thaw method and homogenization with mortar and pestle, Ultrasonic, and Polytron homogenizer) were compared using C. raciborskii. It was found that the efficiency of extraction of phycocyanin was highest when a single freeze–thaw cycle was followed by sonication (25% additional yield compared with using the freeze–thaw method alone). Applying this combined method to surface water samples of Lake Balaton, a strong correlation was found between PC concentration and cyanobacterial biomass (R 2 = 0.9436), whilst the repeated freezing–thawing method found no detectable PC content. Here we show that the combined sonication/freeze–thaw method could be suitable for measuring filamentous cyanobacteria PC content, even at low concentrations; as well as for the estimation of cyanobacterial contribution to total biomass in fresh waters

Detection of Abrin-Like and Prepropulchellin-Like Toxin Genes and Transcripts Using Whole Genome Sequencing and Full-Length Transcript Sequencing of Abrus precatorius

The sequenced genome and the leaf transcriptome of a near relative of Abrus pulchellus and Abrus precatorius was analyzed to characterize the genetic basis of toxin gene expression. From the high-quality genome assembly, a total of 26 potential coding regions were identified that contain genes with abrin-like, pulchellin-like, and agglutinin-like homology, with full-length transcripts detected in leaf tissue for 9 of the 26 coding regions. All of the toxin-like genes were identified within only five isolated regions of the genome, with each region containing 1 to 16 gene variants within each genomic region (<1 Mbp). The Abrusprecatorius cultivar sequenced here contains genes which encode for proteins that are homologous to certain abrin and prepropulchellin genes previously identified, and we observed substantial diversity of genes and predicted gene products in Abrus precatorius and previously characterized toxins. This suggests diverse toxin repertoires within Abrus, potentially the results of rapid toxin evolution.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Ventricular volume asymmetry as a novel imaging biomarker for disease discrimination and outcome prediction

Aims: Disruption of the predictable symmetry of the healthy heart may be an indicator of cardiovascular risk. This study defines the population distribution of ventricular asymmetry and its relationships across a range of prevalent and incident cardiorespiratory diseases. Methods and results: The analysis includes 44 796 UK Biobank participants (average age 64.1 ± 7.7 years; 51.9% women). Cardiovascular magnetic resonance (CMR) metrics were derived using previously validated automated pipelines. Ventricular asymmetry was expressed as the ratio of left and right ventricular (LV and RV) end-diastolic volumes. Clinical outcomes were defined through linked health records. Incident events were those occurring for the first time after imaging, longitudinally tracked over an average follow-up time of 4.75 ± 1.52 years. The normal range for ventricular symmetry was defined in a healthy subset. Participants with values outside the 5th-95th percentiles of the healthy distribution were classed as either LV dominant (LV/RV > 112%) or RV dominant (LV/RV < 80%) asymmetry. Associations of LV and RV dominant asymmetry with vascular risk factors, CMR features, and prevalent and incident cardiovascular diseases (CVDs) were examined using regression models, adjusting for vascular risk factors, prevalent diseases, and conventional CMR measures. Left ventricular dominance was linked to an array of pre-existing vascular risk factors and CVDs, and a two-fold increased risk of incident heart failure, non-ischaemic cardiomyopathies, and left-sided valvular disorders. Right ventricular dominance was associated with an elevated risk of all-cause mortality. Conclusion: Ventricular asymmetry has clinical utility for cardiovascular risk assessment, providing information that is incremental to traditional risk factors and conventional CMR metrics

Human p53 interacts with the elongating RNAPII complex and is required for the release of actinomycin D induced transcription blockage

The p53 tumour suppressor regulates the transcription initiation of selected genes by binding to specific DNA sequences at their promoters. Here we report a novel role of p53 in transcription elongation in human cells. Our data demonstrate that upon transcription elongation blockage, p53 is associated with genes that have not been reported as its direct targets. p53 could be co-immunoprecipitated with active forms of DNA-directed RNA polymerase II subunit 1 (RPB1), highlighting its association with the elongating RNA polymerase II. During a normal transcription cycle, p53 and RPB1 are localised at distinct regions of selected non-canonical p53 target genes and this pattern of localisation was changed upon blockage of transcription elongation. Additionally, transcription elongation blockage induced the proteasomal degradation of RPB1. Our results reveal a novel role of p53 in human cells during transcription elongation blockage that may facilitate the removal of RNA polymerase II from DNA

Komplex molekuláris genetikai vizsgálati algoritmus myeloproliferativ neoplasiák diagnosztikájában

Introduction: Mutations in Janus kinase 2, calreticulin and thrombopoietin receptor genes have been identified in the genetic background of Philadelphia chromosome negative, "classic" myeloproliferative neoplasms. Aim: The aim of the authors was to identify driver mutations in a large myeloproliferative cohort of 949 patients. Method: A complex array of molecular techniques (qualitative and quantitative allele-specific polymerase chain reactions, fragment analyzes, high resolution melting and Sanger sequencing) was applied. Results: All 354 patients with polycythemia vera carried Janus kinase 2 mutations (V617F 98.6%, exon 12: 1.4%). In essential thrombocythemia (n = 468), the frequency of V617F was 61.3% (n = 287), that of calreticulin 25.2% (n = 118), and that of thrombopoietin receptor mutations 2.1% (n = 10), while 11.3% (n = 53) were triple-negative. Similar distribution was observed in primary myelofibrosis (n = 127): 58.3% (n = 74) V617F, 23.6% (n = 30) calreticulin, 6.3% (n = 8) thrombopoietin receptor mutation positive and 11.8% (n = 15) triple-negative. Conclusions: The recent discovery of calreticulin gene mutations led to definite molecular diagnostics in around 90% of clonal myeloproliferative cases. Orv. Hetil., 2014, 155(52), 2074-2081

Distinct clinical characteristics of myeloproliferative neoplasms with calreticulin mutations

Somatic insertions/deletions in the calreticulin gene have recently been discovered to be causative alterations in myeloproliferative neoplasms. A combination of qualitative and quantitative allele-specific polymerase chain reaction, fragment-sizing, high resolution melting and Sanger-sequencing was applied for the detection of three driver mutations (in Janus kinase 2, calreticulin and myeloproliferative leukemia virus oncogene genes) in 289 cases of essential thrombocythemia and 99 cases of primary myelofibrosis. In essential thrombocythemia, 154 (53%) Janus kinase 2 V617F, 96 (33%) calreticulin, 9 (3%) myeloproliferative leukemia virus oncogene gene mutation-positive and 30 triple-negative (11%) cases were identified, while in primary myelofibrosis 56 (57%) Janus kinase 2 V617F, 25 (25%) calreticulin, 7 (7%) myeloproliferative leukemia virus oncogene gene mutation-positive and 11 (11%) triple-negative cases were identified. Patients positive for the calreticulin mutation were younger and had higher platelet counts compared to Janus kinase 2 mutation-positive counterparts. Calreticulin mutation-positive patients with essential thrombocythemia showed a lower risk of developing venous thrombosis, but no difference in overall survival. Calreticulin mutation-positive patients with primary myelofibrosis had a better overall survival compared to that of the Janus kinase 2 mutation-positive (P=0.04) or triple-negative cases (P=0.01). Type 2 calreticulin mutation occurred more frequently in essential thrombocythemia than in primary myelofibrosis (P=0.049). In essential thrombocythemia, the calreticulin mutational load was higher than the Janus kinase 2 mutational load (P<0.001), and increased gradually in advanced stages. Calreticulin mutational load influenced blood counts even at the time point of diagnosis in essential thrombocythemia. We confirm that calreticulin mutation is associated with distinct clinical characteristics and explored relationships between mutation type, load and clinical outcome

Arthritis psoriaticával társuló középsúlyos és súlyos psoriasis betegségterhe Magyarországon

INTRODUCTION: Psoriasis is a frequent, chronic, systemic immune-mediated disease mainly affecting the skin and joints. AIM: To assess health related quality of life and cost-of-illness in moderate to severe psoriasis associated with psoriatic arthritis. METHOD: A cross-sectional questionnaire survey was conducted at two academic dermatology clinics in Hungary. RESULTS: Fifty-seven patients (65% males) completed the survey with a mean age of 54.3+/-11.6 years and mean EQ-5D score of 0.48+/-0.4. Mean annual total cost was euro8,977 per patient, of which 71% occurred due to biological therapy and 21% were indirect costs, respectively. Permanent work disability due to psoriasis accounted for euro1,775 (95% of the indirect costs). Per patient costs of subgroups not receiving systemic therapy (21%), traditional systemic therapy (32%), and biological systemic therapy (47%) amounted to the sum of euro1,729, euro1,799, and euro16,983, respectively. CONCLUSIONS: Patients on biological therapy showed significantly better health related quality of life. As for health economics, the efficacy of systemic treatments is appropriate to be assessed together in patients with moderate to severe psoriasis associated with psoriatic arthritis, since actual health gain might exceed that reported in psoriasis or psoriatic arthritis separately. Orv. Hetil., 2014, 155(48), 1913-1921