Comparative cytogenetics of three species of Dichotomius (Coleoptera, Scarabaeidae)

Meiotic and mitotic chromosomes of Dichotomius nisus, D. semisquamosus and D. sericeus were analyzed after conventional staining, C-banding and silver nitrate staining. In addition, Dichotomius nisus and D. semisquamosus chromosomes were also analyzed after fluorescent in situ hybridization (FISH) with an rDNA probe. The species analyzed had an asymmetrical karyotype with 2n = 18 and meta-submetacentric chromosomes. The sex determination mechanism was of the Xyp type in D. nisus and D. semisquamosus and of the Xy r type in D. sericeus. C-banding revealed the presence of pericentromeric blocks of constitutive heterochromatin (CH) in all the chromosomes of the three species. After silver staining, the nucleolar organizer regions (NORs) were located in autosomes of D. semisquamosus and D. sericeus and in the sexual bivalent of D. nisus. FISH with an rDNA probe confirmed NORs location in D. semisquamosus and in D. nisus. Our results suggest that chromosome inversions and fusions occurred during the evolution of the group

Formation of Complex and Unstable Chromosomal Translocations in Yeast

Genome instability, associated with chromosome breakage syndromes and most human cancers, is still poorly understood. In the yeast Saccharomyces cerevisiae, numerous genes with roles in the preservation of genome integrity have been identified. DNA-damage-checkpoint-deficient yeast cells that lack Sgs1, a RecQ-like DNA helicase related to the human Bloom's-syndrome-associated helicase BLM, show an increased rate of genome instability, and we have previously shown that they accumulate recurring chromosomal translocations between three similar genes, CAN1, LYP1 and ALP1. Here, the chromosomal location, copy number and sequence similarity of the translocation targets ALP1 and LYP1 were altered to gain insight into the formation of complex translocations. Among 844 clones with chromosomal rearrangements, 93 with various types of simple and complex translocations involving CAN1, LYP1 and ALP1 were identified. Breakpoint sequencing and mapping showed that the formation of complex translocation types is strictly dependent on the location of the initiating DNA break and revealed that complex translocations arise via a combination of interchromosomal translocation and template-switching, as well as from unstable dicentric intermediates. Template-switching occurred between sequences on the same chromosome, but was inhibited if the genes were transferred to different chromosomes. Unstable dicentric translocations continuously gave rise to clones with multiple translocations in various combinations, reminiscent of intratumor heterogeneity in human cancers. Base substitutions and evidence of DNA slippage near rearrangement breakpoints revealed that translocation formation can be accompanied by point mutations, and their presence in different translocation types within the same clone provides evidence that some of the different translocation types are derived from each other rather than being formed de novo. These findings provide insight into eukaryotic genome instability, especially the formation of translocations and the sources of intraclonal heterogeneity, both of which are often associated with human cancers

Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human μ-Opioid and Opioid Receptor-Like 1 Receptors

Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human μ-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors

"Adaptive response" - some underlying mechanisms and open questions

Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection, e. g. of astronauts during long-term space flights. In this mini-review we discuss some open questions and the probable underlying mechanisms involved in adaptive response: the transcription of many genes and the activation of numerous signaling pathways that trigger cell defenses - DNA repair systems, induction of proteins synthesis, enhanced detoxification of free radicals and antioxidant production.Publisher PDFPeer reviewe

MEASUREMENT OF BEAM PHASE USING PHASE PROBE AT THE NIRS-930 CYCLOTRON

The NIRS-930 cyclotron of the National Institute of Radiological Sciences (NIRS) has been used for production of short-lived radio-pharmaceuticals for PET, research of physics, developments of particle detectors in space, and so on[1]. The NIRS-930 has twelve trim coils for generation of the isochronous fields. Until recently, currents of the twelve trim coils had been adjusted only by monitoring the output beam intensity. In order to exactly produce the isochronous fields, a phase probe has been installed in the NIRS-930. The beam phase excursion could be reduced within 10 degree

Development of a compact ECR ion source for various ion production

There is a desire that a carbon-ion radiotherapy facility will produce various ion species for fundamental research. Although the present Kei2-type ion sources are dedicated for the carbon-ion production, a future ion source is expected: 1) carbon-ion production for medical use, 2) various ions with a charge-to-mass ratio of 1/3 for the existed linac injector, and 3) low cost for modification. A prototype compact electron cyclotron resonance (ECR) ion source, named Kei3, based on Kei series has been developed to correspond to produce these various ions at National Institute of Radiological Sciences (NIRS). The Kei3 has an outer diameter of 280 mm and a length of 1120 mm. The magnetic field is formed by the same permanent magnet as Kei2. The movable extraction electrode has been installed in order to optimize the beam extraction with various current densities. The gas-injection side of vacuum chamber has enough space for an oven system. We measured dependence of microwave frequency, extraction voltage, and puller position. Charge state distributions of helium, carbon, nitrogen, oxygen, and neon were also measured.16th International Conference on Ion Sources (ICIS2015

The Multi Particle Simulation for the Cyclotron NIRS-930

The simulation of the beam for the cyclotron NIRS-930 at NIRS has been performed with the use of the SNOP program* in order to study beam dynamics in a cyclotron and to improve beam intensity. SNOP simulated from beam injection to extraction with the electric fields of the inflector, the Dee electrodes and the deflector; the magnetic fields of the main coils, the trim coils and the harmonic coils and the magnetic channel which were calculated by OPERA-3d. The simulation of proton with 30 MeV extraction energy with harmonic number of 1 was already performed and well simulated RF phase and extraction efficiency**. Then we tried to apply SNOP to 18 MeV protons with harmonic 2. We first formed isochronous magnetic field with main and trim coils for simulating single particle. Next we optimized electric deflector and magnetic channel in order to maximize extraction efficiency simulating the bunch of particles. Beam loss of the simulation was compared to the experiment. We intend to apply optimized simulation parameters for actual cyclotron operation to improve beam intensity and quality