Interspecific introgression of MHC genes in Triturus newts: evidence from multiple contact zones

The major histocompatibility complex (MHC) genes are central to the adaptive immune response in vertebrates. Selection generally maintains high MHC variation because the spectrum of recognized pathogens depends on MHC polymorphism. Novel alleles favoured by selection originate by interallelic recombination or de novo mutations but may also be acquired by introgression from related species. However, the extent and prevalence of MHC introgression remain an open question. In this study, we tested for MHC introgression in six hybrid zones formed by six Triturus newt species. We sequenced and genotyped the polymorphic second exons of the MHC class I and II genes and compared their interspecific similarity at various distances from the centre of the hybrid zone. We found evidence for introgression of both MHC classes in the majority of examined hybrid zones, with support for a more substantial class I introgression. Furthermore, the overall MHC allele sharing outside of hybrid zones was elevated between pairs of Triturus species with abutting ranges, regardless of the phylogenetic distance between them. No effect of past hybrid zone movement on MHC allele sharing was found. Finally, using previously published genome-wide data, we demonstrated that MHC introgression was more extensive than genome-wide introgression, supporting its adaptive potential. Our study thus provides evidence for the prevalence of MHC introgression across multiple Triturus hybrid zones, indicating that MHC introgression between divergent hybridizing species may be widespread and adaptive.Animal science

Using muon rings for the optical throughput calibration of the SST-1M prototype for the Cherenkov Telescope Array

Imaging Atmospheric Cherenkov Telescopes (IACTs) are ground-based instruments devoted to the study of very high energy gamma-rays coming from space. The detection technique consists of observing images created by the Cherenkov light emitted when gamma rays, or more generally cosmic rays, propagate through the atmosphere. While in the case of protons or gamma-rays the images present a filled and more or less elongated shape, energetic muons penetrating the atmosphere are visualised as characteristic circular rings or arcs. A relatively simple analysis of the ring images allows the reconstruction of all the relevant parameters of the detected muons, such as the energy, the impact parameter, and the incoming direction, with the final aim to use them to calibrate the total optical throughput of the given IACT telescope. We present the results of preliminary studies on the use of images created by muons as optical throughput calibrators of the single mirror small size telescope prototype SST-1M proposed for the Cherenkov Telescope Array.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

DigiCam - Fully Digital Compact Read-out and Trigger Electronics for the SST-1M Telescope proposed for the Cherenkov Telescope Array

The SST-1M is one of three prototype small-sized telescope designs proposed for the Cherenkov Telescope Array, and is built by a consortium of Polish and Swiss institutions. The SST-1M will operate with DigiCam - an innovative, compact camera with fully digital read-out and trigger electronics. A high level of integration will be achieved by massively deploying state-of-the-art multi-gigabit transmission channels, beginning from the ADC flash converters, through the internal data and trigger signals transmission over backplanes and cables, to the camera's server link. Such an approach makes it possible to design the camera to fit the size and weight requirements of the SST-1M exactly, and provide low power consumption, high reliability and long lifetime. The structure of the digital electronics will be presented, along with main physical building blocks and the internal architecture of FPGA functional subsystems.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Software design for the control system for Small-Size Telescopes with single-mirror of the Cherenkov Telescope Array

The Small-Size Telescope with single-mirror (SST-1M) is a 4 m Davies-Cotton telescope and is among the proposed telescope designs for the Cherenkov Telescope Array (CTA). It is conceived to provide the high-energy ($>$ few TeV) coverage. The SST-1M contains proven technology for the telescope structure and innovative electronics and photosensors for the camera. Its design is meant to be simple, low-budget and easy-to-build industrially. Each device subsystem of an SST-1M telescope is made visible to CTA through a dedicated industrial standard server. The software is being developed in collaboration with the CTA Medium-Size Telescopes to ensure compatibility and uniformity of the array control. Early operations of the SST-1M prototype will be performed with a subset of the CTA central array control system based on the Alma Common Software (ACS). The triggered event data are time stamped, formatted and finally transmitted to the CTA data acquisition. The software system developed to control the devices of an SST-1M telescope is described, as well as the interface between the telescope abstraction to the CTA central control and the data acquisition system.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Prototype of the SST-1M Telescope Structure for the Cherenkov Telescope Array

A single-mirror small-size (SST-1M) Davies-Cotton telescope with a dish diameter of 4 m has been built by a consortium of Polish and Swiss institutions as a prototype for one of the proposed small-size telescopes for the southern observatory of the Cherenkov Telescope Array (CTA). The design represents a very simple, reliable, and cheap solution. The mechanical structure prototype with its drive system is now being tested at the Institute of Nuclear Physics PAS in Krakow. Here we present the design of the prototype and results of the performance tests of the structure and the drive and control system.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Higher efficacy of oral nitrendipine admininstration in comparison with sublingual route. Pharmacokinetic and pharmacodynamic evaluation in hypertensive urgencies

Wstęp Istnieje opinia, że leki hipotensyjne podawane w stanach podwyższonego ciśnienia drogą podjęzykową powodują skuteczniejsze obniżenie ciśnienia niż preparaty podawane drogą doustną. Celem badania była ocena stężeń w surowicy oraz efektu działania: redukcji ciśnienia tętniczego po podaniu drogą podjęzykową [SL], doustną [PO] oraz podjęzykową i doustną [SL + PO] 5 mg nitrendipiny. Materiał i metody Nitrendipinę w kroplach w dawce 5 mg podawano 12 chorym z podwyższonym ciśnieniem tętniczym (średnia wartość 167 &plusmn; 9/108 &plusmn; 9 mm Hg), w wieku 55 &plusmn; 9 lat, o masie ciała 81 &plusmn; 13 kg, w sposób randomizowany, z zastosowaniem placebo, drogą podjęzykową [SL] (utrzymanie leku w jamie ustnej przez 20 min i usunięcie pozostałości), doustną [PO] (połknięcie) oraz podjęzykową i doustną [SL + PO] (utrzymanie leku w jamie ustnej przez 20 min i połknięcie). Wartości ciśnienia rejestrowano za pomocą 24-godzinnej automatycznej rejestracji (SpaceLabs 90207), pomiary wykonywano co 10 minut. Stężenia nitrendipiny oznaczano w 16 próbkach krwi pobieranych w ciągu 8 godzin od podania leku metodą chromatografii cieczowej (HPLC), czułość wynosiła 2 ng/ml. Wyniki Najwyższe stężenia nitrendipiny stwierdzono po podaniu PO: Cmax 32,8 &plusmn; 9 ng/ml (tmax 1,0 h) i po podaniu SL + PO: 33,8 &plusmn; 8 ng/ml (tmax 0,96 h) vs. SL: 15,1 &plusmn; 4 ng/ml (tmax 0,53 h). Porównywano stężenia i biodostępność nitrendipiny podanej 3 metodami po 15 min (0,25 h), gdyż późniejsze różnice wynikały z faktu wchłonięcia po podaniu SL w ciągu 20 minut tylko 2,81 mg leku (56,2% podanej dawki). Stężenia nitrendipiny po 0,25 h od podania wyniosły po podaniu PO: 14,4 &plusmn; 71 ng/ml, SL + PO: 10,1 &plusmn; 6,9 ng/ml, a po SL: 7,3 &plusmn; 3,4 ng/ml. Wartości AUCcałk po podaniu PO wynosiły: 90,5 &plusmn; 35 ng.h/ml (AUC po 0,25 h: 1,5). Wartości AUCcałk po podaniu SL + PO: 60,0 &plusmn; 29 ng.h/ml (AUC po 0,25 h: 0,9). Pole pod krzywą stężenie&#8211;czas po podaniu SL wyniosło tylko 12,8 &plusmn; 7 ng.h/ml (po 0,25 h: 1,1). Wchłanianie leku z przewodu pokarmowego było szybsze niż ze śluzówki jamy ustnej. Redukcja ciśnienia skurczowego [SBP] po 15 minutach wyniosła w porównaniu z placebo, odpowiednio, po podaniu PO: 7,1 mm Hg (p < 0,05), po podaniu SL + PO: 3,2 mm Hg (ns), a po podaniu SL: 5,5 mm Hg (ns). Istotna redukcja SBP wystąpiła po podaniu PO przez okres 0,25&#8211;10 h (maks. w 3 h, &#8211;17,2%) , po podaniu SL + PO przez okres 1&#8211;10 h (maks. 2,5 h, &#8211;14,9%). Redukcja powyżej 10% SBP wystąpiła po 1 h u wszystkich pacjentów po podaniu PO i SL + PO. Po podaniu drogą SL nie stwierdzono istotnej redukcji SBP. Wnioski Wchłanianie nitrendipiny zachodziło szybciej z przewodu pokarmowego po połknięciu leku w porównaniu z podaniem SL. Tylko po podaniu leku PO oraz SL + PO występowało większe i dłużej utrzymujące się obniżenie ciśnienia. W praktyce nie istnieje czysta droga podjęzykowa podania leku: przy poleceniu utrzymywania leku pod językiem jedynie część jest wchłaniana ze śluzówki jamy ustnej, reszta jest połykana i wchłonięta z przewodu pokarmowego.Background In management of hypertensive urgencies the common opinion exists, that antihypertensive drugs given sublingually are more efficacious than administered orally. The aim of the study was to assess plasma concentrations and effect (blood pressure reduction) after sublingual [SL], oral [PO] and sublingual and oral [SL + PO] administration [adm] of 5 mg nitrendipine [NIT]. Material and methods NIT drops, dose 5 mg, were administered to 12 moderate hypertensive patients with mean initial blood pressure 167/108 (&plusmn; 9/9) mm Hg, mean age 55 &plusmn; 9 years, body mass 81 &plusmn; 13 kg. Patients were given NIT randomly in comparison with placebo: sublingually (keeping drops 20 minutes in the mouth and then removing the rest), orally (swallowing drops), and combined (keeping drops in the mouth for 20 min then swallowing). BP was recorded for 24 hrs using ambulatory BP monitoring (SpaceLabs 90207), readings every 10 min. NIT levels were measured in 16 blood samples drawn for 8 hrs after drug intake by HPLC method (sensitivity 2 ng/ml). Results Highest NIT concentrations were measured after POadm: Cmax 32.8 &plusmn; 9 ng/ml (tmax 1.0 h) and after SL + PO: 33.8 &plusmn; 8 ng/ml (tmax 0.96 h) vs. SL 15.1 &plusmn; 4 ng/ml (tmax 0.53). The concentrations and bioavailability of NIT after 3 ways of administration were compared after 15 min (0.25 h), because latter differences were due to low absorption after SL administration within 20 minutes: 2.81 mg only (56.2% given dose). NIT concentrations after 0.25 h were for PO administration: 14.4 &plusmn; 7 ng/ml, SL + PO: 10.1 &plusmn; 6.9 ng/ml and SL: 7.3 &plusmn; 3.4 ng/ml. Total AUC after PO administration was 90.5 &plusmn; 35 ng.h/ml (AUC after 0.25 h: 1.5 ng.h/ml). Total AUC after SL + PO was 60.0 &plusmn; 29 ng.h/ml (AUC after 0.25 h: 0.9). And finally: total AUC after SL administration was only 12.8 &plusmn; 7 ng.h/ml (after 0.25 h: 1.1). This indicated that absorption from GI tract was faster than from oral mucosa. Systolic blood pressure reductions [SBP] after 0.25 was, respectively, for PO administration: 7.1 mm Hg (p < 0.05), SL + PO: 3.2 mm Hg (ns), and for SL: 5.5 mm Hg (ns). Significant SBP reduction was observed after PO administration for 0.25&#8211;10 hrs (max after 3 h, &#8211;17.2%), after SL + PO for 1&#8211;10 hrs (max after 2.5 h, &#8211;14.9%). In all patients 1 h after PO and SL + PO administration > 10% reduction of SBP was registered. After SL no significant reduction of SBP was observed. Conclusions Study demonstrated the faster absorption of NIT from gastro-intestinal tract than from oral mucosa. Only after PO and SL+PO administration greater and prolonged reduction of SBP was observed. The pure sublingual administration does not exist in practice: only small part of drug is absorbed from oral mucosa and most part of drug after swallowing is absorbed from gastro-intestinal tract

Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors

Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find genes, potentially implicated in this cancer. In this study, we focus on the FAM107A (3p14.3) gene, since we found its significantly reduced expression in LSCC by microarray profiling (Affymetrix U133 Plus 2.0 array). By RT-PCR we have confirmed complete FAM107A downregulation in laryngeal cancer cell lines (15/15) and primary tumors (21/21) and this finding was further supported by FAM107A protein immunohistochemistry (15/15). We further demonstrate that a combined two hit mechanism including loss of 3p and hypermethylation of FAM107A promoter region (in 9/15 cell lines (p p FAM107A expression (5 to 6 fold increase) in the UT-SCC-29 cell line, characterized by high DNA methylation. Therefore, we report the recurrent inactivation of FAM107A in LSCC, what may suggest that the gene is a promising tumor suppressor candidate involved in LSCC development.</p