Experimental station with continuous electron beam for investigation of various mechanisms of EM radiation generation

In this report we describe a new facility designed, manufactured and commissioned at Belgorod National Research University. It is a compact and cost-efficient low energy continuous electron beam installation developed to underpin research and education foundation of the University group. We present the measurements of the beam size, emittance, position and trajectory. A THz detection beam line has also been constructed and tested. The status of the THz radiation generation programme, future upgrades and experimental plans have been describe

Loss of tolerance to gut immunity protein; glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis

Abstract Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn’s disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation. PAbs were more frequent in PSC(46.2%) compared to controls(healthy:0% and CLD:4.5%), [P < 0.001, for each]. Occurrence of anti-GP2 antibody was 30.8% (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4% (13/19) of anti-GP2 IgA antibodies were bound with secretory component, suggesting an active retro-transportation of anti-GP2 from the gut lumen to the mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9–99] months) and remained an independent predictor after adjusting for Mayo risk score(HR: 4.69 [1.05–21.04], P = 0.043). These results highlight the significance of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk stratification in PSC and considered as a potential therapeutic target

Rediscovery of the anti-pancreatic antibodies and evaluation of their prognostic value in a prospective clinical cohort of Crohn's patients: the importance of specific target antigens (GP2 and CUZD1).

BACKGROUNDS: Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1] belong to protein families involved in gut innate immunity processes and have recently been identified as specific targets of anti-pancreatic autoantibodies [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of novel target-specific PAbs regarding long-term disease course of an adult CD patient cohort. METHODS: Sera of 458 consecutive well-characterised IBD patients from a single referral IBD centre were tested by enzyme-linked immunosorbent assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG] and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were available on complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up [median, 108 months]. RESULTS: Totals of 12.4% and 20.8% of CD patients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared with UC [p < 0.01]. Antibody status was stable over time. Agreement among three different anti-GP2 assays was good. Positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA [pLogRank < 0.01] or anti-CUZD1 IgA [pLogRank < 0.001] positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in the multivariate Cox-regression model (hazard ratio [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p < 0.001). CONCLUSIONS: The present study has shown that specific PAbs [especially IgA subtype] predict complicated disease course including the development of perianal disease in CD

Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries

The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome domains in various mammalian cell types are described. The visualization of splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed distinctly different distribution patterns in these cell types. Heat shock experiments confirmed that the distribution patterns also depend on physiological parameters. Using a combination of fluorescencein situ hybridization and immunodetection protocols, individual chromosome domains were visualized simultaneously with the Sm antigen or the transcript of an integrated human papilloma virus genome. Three-dimensional analysis of fluorescence-stained target regions was performed by confocal laser scanning microscopy. RNA transcripts and components of the splicing machinery were found to be generally excluded from the interior of the territories occupied by the individual chromosomes. Based on these findings we present a model for the functional compartmentalization of the cell nucleus. According to this model the space between chromosome domains, including the surface areas of these domains, defines a three-dimensional network-like compartment, termed the interchromosome domain (ICD) compartment, in which transcription and splicing of mRNA occurs

Current status of the IAG working group 4.3.7 on geodetic GNSS-R

Presentación realizada online en el Scientific Assembly of the International Association of Geodesy (2021) celebrado del 28 de junio al 2 de julio en Beijing

How to use implantable loop recorders in clinical trials and hybrid therapy

Epidemiological studies show that atrial fibrillation (AF) is associated with a doubling of mortality, even after adjustment for confounders. AF can be asymptomatic, but this does not decrease the thromboembolic risk of the patient. Office ECGs, occasional 24-h Holter recordings and long-term ECG event recording might not be sensitive and accurate enough in patients with AF, especially in those with paroxysmal episodes. In one study, 7 days of continuous monitoring with event recorders detected paroxysmal AF in 20 of 65 patients with a previous negative 24-h Holter recording. Over the last decade, enormous improvements have been made in the technology of implantable devices, which can now store significant information regarding heart rhythm. The first subcutaneous implantable monitor (Reveal XT, Medtronic) was validated for continuous AF monitoring by the XPECT study. The dedicated AF detection algorithm uses irregularity and incoherence of R–R intervals to identify and classify patterns in ventricular conduction. Its sensitivity in identifying patients with AF is >96%. Numerous clinical data from continuous monitoring of AF have recently been published. The first applications of this technology have been in the field of surgical and catheter AF ablation. With regard to cryptogenic stroke, an international randomized trial is ongoing to compare standard care with standard care plus the implantable cardiac monitor for AF detection in patients discharged with the diagnosis of cryptogenic stroke: the Crystal AF trial. Continuous AF monitoring provides an optimal picture of daily AF burden, both symptomatic and asymptomatic. Implantable cardiac monitors have high sensitivity, enable better assessment of therapy success and may guide further AF therapy

Predictive genetic testing for motor neuron disease : time for a guideline?

Predictive (presymptomatic) testing refers to the situation where a person at risk of inheriting a specific condition requests a genetic test to clarify their status. This most commonly occurs in familial cancer, cardiac and neurodegenerative disorders. People seek predictive testing for a variety of reasons including to reduce uncertainty, enable financial planning or access reproductive medicine option

The first whole genome and transcriptome of the cinereous vulture reveals adaptation in the gastric and immune defense systems and possible convergent evolution between the Old and New World vultures

Background: The cinereous vulture, Aegypius monachus, is the largest bird of prey and plays a key role in the ecosystem by removing carcasses, thus preventing the spread of diseases. Its feeding habits force it to cope with constant exposure to pathogens, making this species an interesting target for discovering functionally selected genetic variants. Furthermore, the presence of two independently evolved vulture groups, Old World and New World vultures, provides a natural experiment in which to investigate convergent evolution due to obligate scavenging. Results: We sequenced the genome of a cinereous vulture, and mapped it to the bald eagle reference genome, a close relative with a divergence time of 18 million years. By comparing the cinereous vulture to other avian genomes, we find positively selected genetic variations in this species associated with respiration, likely linked to their ability of immune defense responses and gastric acid secretion, consistent with their ability to digest carcasses. Comparisons between the Old World and New World vulture groups suggest convergent gene evolution. We assemble the cinereous vulture blood transcriptome from a second individual, and annotate genes. Finally, we infer the demographic history of the cinereous vulture which shows marked fluctuations in effective population size during the late Pleistocene. Conclusions: We present the first genome and transcriptome analyses of the cinereous vulture compared to other avian genomes and transcriptomes, revealing genetic signatures of dietary and environmental adaptations accompanied by possible convergent evolution between the Old World and New World vulturesopen