However, controversial results of the associations of NRG1 polymorphisms with schizophrenia and related phenotypes have been reported. In this study, four NRG1 single nucleotide polymorphisms, three in the promoter region, and one nonsynonymous in coding region, were genotyped in a total of 825 subject including 435 schizophrenia cases and 390 normal controls of Korean ethnicity. Although logistic association analysis of NRG1 polymorphisms and haplotypes with schizophrenia showed a nominal association in rs4623364G > C (P = 0.04), the significance disappeared after corrections for multiple testing (corrected P > 0.05). Additional Selleckchem BEZ235 case/control and multiple regression analyses

in schizophrenia patients using a method that measures the smooth pursuit eye movement (SPEM) function globally based on natural logarithmic values of the signal/noise ratio also showed no association Fer-1 between NRG1 variants and SPEM abnormality among

patients with schizophrenia (P > 0.05). Despite the need for further replications in other cohorts, our findings provide additional supporting information that four variants in NRG1 investigated in this study may not be associated with schizophrenia and its related SPEM function in a Korean population.”
“The interactions and processes which structure prokaryotic cytoplasm (water, ions, metabolites, and biomacromolecules) and ensure the fidelity of the cell cycle are reviewed from a physicochemical perspective. Recent spectroscopic and biological evidence shows that water has no active structuring role in the cytoplasm, an unnecessary notion still entertained in the literature;

water acts only as a normal solvent and biochemical reactant. Subcellular structuring arises from localizations and interactions of biomacromolecules and from the growth and modifications of their surfaces by catalytic reactions. Biomacromolecular crowding is a fundamental physicochemical characteristic of cells in vivo. Though some biochemical and physiological effects of crowding (excluded volume effect) have been documented, crowding assays with polyglycols, dextrans, etc., do not properly mimic the compositional variety selleck of biomacromolecules in vivo. In vitro crowding assays are now being designed with proteins, which better reflect biomacromolecular environments in vivo, allowing for hydrophobic bonding and screened electrostatic interactions. I elaborate further the concept of complex vectorial biochemistry, where crowded biomacromolecules structure the cytosol into electrolyte pathways and nanopools that electrochemically “wire” the cell. Noncovalent attractions between biomacromolecules transiently supercrowd biomacromolecules into vectorial, semiconducting multiplexes with a high (35 to 95%)-volume fraction of biomacromolecules; consequently, reservoirs of less crowded cytosol appear in order to maintain the experimental average crowding of similar to 25% volume fraction.

[Methods] Twenty-three participants performed Jebsen-Taylor hand function test and grooved pegboard for task performance and dexterity. The power grip and pinch strength was measured using Jamar hydraulic hand dynamometer and pinch gauge. [Results] In the result of the Jebsen-Taylor hand function test, task performance with the cock-up splint was slower compared to without the splint for all items. Men’s grip power with the cock-up splint was found to be significantly decreased

compared to without buy PF-6463922 the splint. Women’s grip and palmar pinch strength with the splint decreased significantly compared to without the splint. In the grooved pegboard test, the dexterity of both men and women with learn more the cock-up splint decreased significantly compared to without the splint. [Conclusion] To assist patients to make wise decisions regarding the use of splints, occupational

therapists must have empirical knowledge of the topic as well as an understanding of the theoretical, technical, and related research evidence. The results of this study will be useful in the analysis and understanding of changes in hand function in splint applications for people with hand dysfunction.”
“Gold is a valuable metal occurring usually at very low concentrations in complex natural samples. Gold analysis thus needs preconcentration methods. Classical liquid-liquid extraction involves hazardous organic solvents. Alternatively, cloud point extraction involves non-toxic and nonvolatile surfactants. Here, we analyzed ore samples. The complex of Au(III) with sulphapyridylazo resorcin was extracted

by the cloud point method. Concentrations were measured by flame atomic absorption spectrometry. We tested the effects of pH, reagent concentration, Triton X-100 surfactant concentration, equilibration temperature and time. Results show that the best detection limit of the method was 0.48 A mu g L-1 for Au with a preconcentration factor of 31 times. Calibration is linear in range of 6.4-2,000 A mu g L-1, and relative standard deviations are lower than 5 %. Quantum chemical computations reveal the plausible structure of the gold-ligand complex. This report VE-821 mw represents the first determination of gold using sulphapyridylazo resorcin as a ligand.”
“The ORF3 protein of porcine circovirus type 2 (PCV2) causes apoptosis in virus-infected cells and is not essential for virus replication. The ORF3 protein plays an important role in the pathogenesis of the PCV2 infection in mouse models and SPF piglets. The ORF3 protein interacts with the porcine homologue of Pirh2 (pPirh2), a p53-induced ubiquitin-protein E3 ligase, which regulates p53 ubiquitination. Here, we present our study analyzing the details of the molecular interaction between these three factors.

2 years).

The rs25531 polymorphism was genotyped in both groups. Because of its close proximity to rs25531, the 5-HTTLPR promoter polymorphism was also genotyped. Genotype and allele frequencies for rs25531 and for the composite 5-HTTLPR/rs25531 marker were analyzed by chi(2) test.\n\nRESULTS: There was no significant association between any genotype and clinical category and no significant allele distribution profiles for rs25531 or 5-HTTLPR/rs25531 in either the premenstrual dysphoric disorder or the control groups.\n\nCONCLUSION: These findings do not support a major role for rs25531, either in isolation or combined with 5-HTTLPR, in contributing to susceptibility to premenstrual dysphoria.”
“OBJECTIVES selleck products This study sought to evaluate the impact of chronic kidney disease (CKD) on coronary atherosclerotic plaque composition, morphology, and outcomes in patients with acute coronary GS-9973 in vitro syndromes (ACS).\n\nBACKGROUND CKD patients presenting with ACS are at increased risk for adverse events. Whether or not this increased risk reflects differences in coronary plaque composition remains unknown.\n\nMETHODS In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with ACS in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and radiofrequency intravascular ultrasound imaging. Lesions

were prospectively characterized, and patients were followed for a median of 3.4 years. We conducted a patient-level and lesion-level analysis of study participants by comparing intravascular ultrasound parameters of untreated nonculprit lesions in patients with and without CKD.\n\nRESULTS Patients with CKD (n = 73, 11.3%) were older, more click here often female and diabetic compared to those without CKD (n = 573). Nonculprit lesions in patients with (n = 280) versus without (n = 2,390)

CKD were more likely to have plaque burden >= 70% (11.8% vs. 8.5%, p = 0.05) and minimal luminal area >= 4.0 mm(2) (25.9% vs. 19.2%, p = 0.005). The percentage of plaque comprised of necrotic core (15.0% vs. 13.0%, p = 0.0001) and dense calcium (8.2% vs. 6.4%, p < 0.0001) was higher while fibrous tissue (57.7% vs. 59.8%, p < 0.0001) was lower in CKD versus non-CKD lesions. The 3-year composite rate of cardiac death, cardiac arrest, or myocardial infarction (15.1% vs. 3.3%, p < 0.0001) was significantly higher in patients with than in those without CKD, although there were no differences in the rates of events adjudicated to nonculprit lesions.\n\nCONCLUSIONS Following percutaneous coronary intervention of all culprit lesions in ACS, patients with versus without CKD have more extensive and severe atherosclerosis remaining in their coronary tree with plaque composed of greater necrotic core and less fibrous tissue.

Response rates and time to relapse vary significantly

among treated individuals. The objective of this study was to monitor the response of seropositive and seronegative RA patients GSK1120212 in vivo to rituximab and correlate relapse with B-cell markers in the two groups.\n\nMethods: Seventeen RA patients (eight seropositive for rheumatoid factor [RF+] and nine seronegative [RF-]) were treated with two cycles of rituximab. After treatment, all patients were re-evaluated at the outpatient clinic, and rituximab was readministered when disease relapse was confirmed by clinical-laboratory measures (Disease Activity Score [DAS]-28). CD20+ cells and CD20 receptor expression levels were estimated at initiation, relapse, and re-evaluation timepoints, and were compared between the two groups.\n\nResults: Seropositive patients responded favorably to treatment compared with the seronegative group. The mean time to relapse was 337.5 +/- 127.0 days for the RF+ patients versus 233.3 +/- 59.6 days for the RF-patients (p = 0.043), despite more aggressive concomitant treatment in the seronegative group. The DAS28 decrease 3 months

after treatment was 1.695 +/- 1.076 in seropositive patients versus 0.94 +/- 1.62 in seronegative patients. At relapse, DAPT Proteases inhibitor CD20 receptor expression (molecules/cell) was higher in RF+ patients than in their RF- counterparts, despite a significantly lower percentage of CD20+ cells.\n\nConclusion: Rituximab treatment is efficient in both seropositive and seronegative RA. However, seropositive RA patients tend to respond favorably compared with seronegative patients. The differential CD20 receptor expression

in the two groups at relapse potentially suggests a different pathogenetic mechanism of relapse and merits further investigation.”
“Trehalose, https://www.selleckchem.com/products/cbl0137-cbl-0137.html a nonreducing disaccharide of glucose, is synthesized as a stress response factor when cells are exposed to stressful conditions. In the cornea, oxidative stress plays the key role in the development of acute corneal inflammatory response to UVB rays, photokeratitis. We found previously that trehalose reduced UVB-induced oxidative effects on the formation of cytotoxic peroxynitrite, apoptotic corneal epithelial cell death and changes in corneal optics. The aim of the present study was to examine whether trehalose might inhibit UVB-mediated proinflammatory cytokine and matrix metalloproteinase induction and the development of an antioxidant/pro-oxidant imbalance in the corneal epithelium, changes found previously to be strongly involved in the acute corneal UVB-induced inflammation. The expression of heat shock protein 70 as a potential biomarker for corneal UVB-induced damage was also examined.\n\nThe corneas of New Zealand white rabbits were irradiated with UVB rays, 312 nm, daily dose of 0.5 J/cm(2) for 4 days.

This paper reports on how the presence of wave-like disturbances in a time series, can lead to an overestimation of turbulence statistics, errors when calculating the stability parameter, erroneous estimation of the friction velocity u* used to screen flux data, and errors in turbulent flux calculations. Using time series of the pressure signal from a microbarograph, wavelike disturbances at an AmeriFlux site are identified. The wave-like disturbances are removed during

the calculation of turbulence statistics and turbulent fluxes. Our PCI-32765 cost findings suggest that filtering eddy-covariance data in the presence of wave-like events prevents both an overestimation of turbulence statistics and errors in turbulent flux calculations. Results show that large-amplitude wave-like events, events surpassing three standard deviations, occurred on 18% of the nights considered in the present study. Remarkably, on flux towers located in a very stably stratified boundary-layer GDC 0032 ic50 regime, the presence of a gravity wave can enhance turbulence statistics more than 50 %. In addition, the presence of the disturbance modulates the calculated turbulent fluxes of CO2 resulting in erroneous turbulent flux calculations of the order of 10% depending on averaging time and pressure perturbation

threshold criteria. Furthermore, the friction velocity u* was affected by the presence of the wave, and in at least one case, a 10% increase caused u* to exceed the arbitrary 0.25 m s(-1) threshold used in many studies. This results in an unintended bias in the data selected for analysis in the flux calculations. The impact of different averaging periods was also examined and found to be variable specific. These early case study results provide an insight into errors introduced when calculating “purely”

turbulent fluxes. These results could contribute to improving modeling efforts by providing more accurate inputs of both turbulent kinetic energy, and isolating the turbulent component of u* for flux selection in the stable nocturnal boundary layer.”
“The electrochemical MLN4924 chemical structure behaviour of Ti-Ni shape memory alloy and Co-Cr alloys were investigated in dynamic Tyrode’s simulated body fluid on a Model CP6 Potentiostat/Galvanostat. The results indicated that, for all alloys, the anodic dissolution and the pitting sensitivity increased with the flow rate of the Tyrode’s solution increasing while the open-circuit potentials and pitting corrosion potentials decreased with the Tyrode’s solution increasing. Pitting corrosion of Ti-Ni alloy was easier than Co-Cr alloys. Since the solution’s flow enhanced oxygen transform and made it easy to reach the surface of electrodes, the plateau of oxygen diffusion control was diminished.

We characterized the centrosomal status, ploidy, and gene status (TP53, CDKN2A/B, BRAF, and NRAS) of 15 human metastatic melanoma cell

lines. Cells were labelled for pericentrin (a centrosomal marker), DNA and alpha-tubulin, and scored for centrosome morphology, supernumerary centrosomes, and mitotic symmetry. The incidence of supernumerary centrosomes correlated with that of gross centrosomal abnormalities (r = 0.90), mitotic asymmetry (r = 0.90), and, surprisingly, increased content of G/M cells (r = INCB28060 order 0.79). Centrosomal numerical dysregulation, observed in all cell lines, was found not to be specifically related to the status of any of the characterized gene mutations that were found in 13/15 cell lines.

We conclude that centrosomal dysregulation may arise from multiple mechanisms and may drive the generation of genetic and phenotypic diversity in melanoma.”
“Great attention is devoted to persistent organic pollutant (POP), among which the pesticide dicofol is critical related to food safety and might raise the risk of cancer incidence. To take a comprehensive evaluation of its toxicity, we investigated its interaction with a serine protease alpha-chymotrypsin by multispectroscopic techniques and molecular modeling method. UV-vis absorption, synchronous fluorescence, and circular dichroism data elucidated that dicofol unfolded the framework of alpha-chymotrypsin and led to secondary structure changes. The fluorescence and lifetime assay determined the static quenching mode and binding parameters. As an auxiliary method, molecular modeling Selleckchem XMU-MP-1 has

displayed the specific MI-503 binding site and information about binding forces and drug-residues distances which were consistent with conclusions from above. Additional, enzyme activity assay gave evidence at the functional aspect to clarify the fact that dicofol could contribute to the conformational changes and furthermore alter the function of the enzyme. (C) 2012 Elsevier Ltd. All rights reserved.”
“DesA3 (Rv3229c) from Mycobacterium tuberculosis is a membrane-bound stearoyl coenzyme A Delta(9) desaturase that reacts with the oxidoreductase Rv3230c to produce oleic acid. This work provides evidence for a mechanism used by mycobacteria to regulate this essential enzyme activity. DesA3 expressed as a fusion with either a C-terminal His(6) or c-myc tag had consistently higher activity and stability than native DesA3 having the native C-terminal sequence of LAA, which apparently serves as a binding determinant for a mycobacterial protease/degradation system directed at DesA3. Fusion of only the last 12 residues of native DesA3 to the C terminus of green fluorescent protein (GFP) was sufficient to make GFP unstable. Furthermore, the comparable C-terminal sequence from the Mycobacterium smegmatis DesA3 homolog Msmeg_1886 also conferred instability to the GFP fusion.

The Hamilton Depression Rating Scale (HDRS) was also applied for comparative purposes.\n\nResults: Our results demonstrate that the SHAPS in its spanish version

maintains the validity and reliability level of the original english find more version. A moderate internal consistency was determined by Cronbach alpha value of 0.77.\n\nConclusion: our results demonstrate the the spanish version of the SHAPS has validity and reliability similar to its original version, and thus it represents a good alternative to evaluate anhedonia in spanish-speaking populations.”
“Plant growth promoting rhizobacteria (PGPR) has been a focus of research for its potential as an eco-friendly alternative to chemical fertilizers in the agriculture industry. In current study, the effect of culture suspension

(CS) of a novel gibberellins (GAs) producing bacterial strain Burkholderia sp. KCIC 11096BP, was observed on shoot length, shoot fresh and dry biomass, root fresh and dry biomass, chlorophyll contents, endogenous bioactive GAs (GA(1) and GA(4)) and their immediate precursors, abscisic acid (ABA), soluble sugar contents and crude protein contents of cucumber (Cucumis sativus L). We found that growth attributes of cucumber were significantly promoted by the application of CS of Burkholderia sp. KCTC 11096BR The quantity of GA(1) and GA(4) and their immediate precursors GA(20) and GA(9) respectively, were also significantly promoted as compared to their respective controls. Contrary to GAS, the quantity of endogenous free ABA in cucumber leaves was much lower in bacterial CS treated plants. Soluble sugar contents MGCD0103 and crude protein contents of cucumber leaves were also significantly higher in bacterial CS treatments as compared to control. It was concluded that Burkholderia sp. KCTC 11096BP can be used as an eco-friendly bio-fertilizer in our farming systems. (C) 2010 Elsevier Masson

SAS. All rights reserved.”
“BackgroundOverweight MEK inhibitor or obese individuals with type 2 diabetes are encouraged to lose weight for optimal glucose management, yet many find this difficult. Determining whether alterations in dietary patterns irrespective of weight loss can aid glucose control has not been fully investigated. MethodsWe conducted a systematic review and meta-analysis aiming to determine the effects of a Mediterranean diet compared to other dietary interventions on glycaemic control irrespective of weight loss. Electronic databases were searched for controlled trials that included a Mediterranean diet intervention. The interventions included all major components of the Mediterranean diet and were carried out in free-living individuals at high risk or diagnosed with type 2 diabetes. Network meta-analysis compared all interventions with one another at the same time as maintaining randomisation. Analyses were conducted within a Bayesian framework.

This review focuses on the various patterns of CNS tuberculosis and various modalities used for the diagnosis.”
“Objectives Morphological changes of the pelvic floor during pregnancy and delivery can be visualized by three-dimensional (3D) perineal ultrasound. The aim of this study was Selleck Ilomastat to compare biometric measurements of the levator ani muscle according to maternal constitutional factors, delivery mode and size of the baby immediately after the first delivery.\n\nMethods In this prospective observational study, 130 primiparae were recruited (all of them Caucasians with singleton pregnancy and cephalic presentation). A 3D perineal ultrasound

scan was performed on the second day after delivery with standardized settings. Volumes were obtained at rest and on Valsalva maneuver, and biometric measurements of the levator hiatus were determined in the axial plane. Different obstetric and constitutional parameters were obtained from our clinical files.\n\nResults All biometric measurements of the levator hiatus were significantly greater in the vaginal delivery group

than in the Cesarean section group (P < 0.001), whereas subgroup analysis within the vaginal (spontaneous vs. operative vaginal) and Cesarean (primary DMXAA in vitro vs. secondary) delivery groups did not show statistically significant differences. There was no demonstrable influence of maternal constitutional factors (age, body mass index (BMI)) or different obstetric parameters (length of second stage of labor, episiotomy, maternal injuries) on levator hiatus size postpartum, even in subgroups that delivered vaginally. Women with de novo postpartum stress incontinence showed a significantly higher mean levator hiatus transverse diameter and larger hiatal area on Valsalva maneuver (P < 0.05). There was also a positive but very weak correlation between the newborn’s head circumference and hiatal dimensions at Valsalva maneuver (P < 0.05).\n\nConclusions Pelvic floor imaging by 3D ultrasound this website is easily accessible even on the first days after delivery and can provide useful information on morphological changes of the levator ani muscle. In our study,

women with vaginal or operative vaginal delivery had a significantly larger hiatal area and transverse diameter than women who delivered by Cesarean section. Maternal constitutional factors (BMI, age) and duration of second stage of labor had no influence on the biometric measurements of hiatal area, whereas weight and head circumference of the baby showed a positive correlation with area of the levator hiatus. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.”
“A codon-optimized Aspergillus niger pectin methylesterase (PME) gene was expressed in the methylo-trophic yeast Canidia boidinii. The PME-producing strains showed better growth on pectin than the wild-type strains, suggesting that the PME-producing strains could efficiently utilize methyl ester moieties of pectin.

4% (95% confidence interval=3.5-5.3) and 1.5% (95% confidence interval=1.0-2.0), respectively. Among HCV RNA carriers, genotyping showed that HCV genotypes 2 and 3 were the most prevalent as they were detected in

18 (56.3%) and 5 (15.6%) individuals, respectively. HCV genotypes la and 4 were the least frequent among the blood donors. HCV mixed genotypes 2/3 and 2/4 were also detected among the blood donors. Conclusion. The prevalence of HCV found in this study is lower than previously reported prevalences. Large-scale studies are needed to obtain a better picture of the molecular epidemiology of HCV in Burkina Faso.”
“Background: In published case reports, tocilizumab (TCZ) has www.selleckchem.com/products/INCB18424.html shown good efficacy for AA amyloidosis in almost all patients. We investigated the efficacy and Cell Cycle inhibitor safety of TCZ in AA amyloidosis in a multicentre study of unselected cases. Methods: We e-mailed rheumatology and internal medicine departments in France, Switzerland and North Africa by using the Club Rhumatismes Inflammation (CRI) network and the French TCZ registry, Registry RoAcTEmra (REGATE), to gather data on consecutive patients with histologically proven AA amyloidosis who had received at least one TCZ infusion. Efficacy

was defined as a sustained decrease in proteinuria level and/or stable or improved glomerular filtration rate (GFR) and by TCZ maintenance. Results: We collected 12 cases of AA amyloidosis treated with TCZ as monotherapy (mean age of patients 63 +/- 16.2 years, amyloidosis duration selleck inhibitor 20.6 +/- 31.3 months): eight patients had rheumatoid arthritis (RA), six with

previous failure of anti-tumor necrosis factor alpha (anti-TNF-alpha) therapy. In total, 11 patients had renal involvement, with two already on hemodialysis (not included in the renal efficacy assessment). For the nine other patients, baseline GFR and proteinuria level were 53.6 +/- 32.8 mL/min and 5 +/- 3.3 g/24 h, respectively. The mean follow-up was 13.1 +/- 11 months. TCZ was effective for six of the eight RA patients (87.5%) according to European League Against Rheumatism response criteria (four good and two moderate responders). As expected, C-reactive protein (CRP) level decreased with treatment for 11 patients. Renal amyloidosis (n = 9) progressed in three patients and was stabilized in three. Overall, three patients showed improvement, with sustained decrease in proteinuria level (42%, 82% and 96%). Baseline CRP level was higher in subsequent responders to TCZ than other patients (p = 0.02). Among the six RA patients with previous anti-TNF-alpha therapy, amyloidosis was ameliorated in one and stabilized in three. Three serious adverse events occurred (two diverticulitis and one major calciphylaxia due to renal failure). Finally, 7 of 12 (58%) patients continued TCZ. Conclusions: The efficacy of TCZ for AA amyloidosis varies depending on the inflammatory status at treatment onset.

htt(-) cells also failed to maintain myosin II in the cortex of the cleavage furrow, generating unseparated daughter cells connected through a thin cytoplasmic bridge. Furthermore, similar to Dictyostelium htt(-) cells, siRNA-mediated knockdown of human HTT also decreased the PP2A activity in HeLa cells. Our data indicate that Htt regulates the phosphorylation status of myosin II during chemotaxis and cytokinesis through PP2A.”
“D-(+)-Galactose-conjugated single-walled carbon nanotubes (SWCNTs)

were synthesized for use as biosensors to detect Saracatinib research buy the cancer marker galectin-3. To investigate the binding of galectin-3 to the D-(+)-galactose-conjugated SWCNTs, an electrochemical biosensor

was fabricated by using molybdenum electrodes. The binding affinities of the conjugated SWCNTs to galectin-3 LY2606368 chemical structure were quantified using electrochemical sensitivity measurements based on the differences in resistance together with typical I-V characterization. The electrochemical sensitivity measurements of the D-(+)-galactose-conjugated SWCNTs differed significantly between the samples with and without galectin-3. This indicates that D-(+)-galactose-conjugated SWCNTs are potentially useful electrochemical biosensors for the detection of cancer marker galectin-3.”
“Background: Paphiopedilum is a horticulturally and ecologically important genus of ca. 80 species of lady’s slipper orchids native to Southeast Asia. These plants have long been of ASP2215 Protein Tyrosine Kinase inhibitor interest regarding their chromosomal evolution, which involves a progressive aneuploid series based

on either fission or fusion of centromeres. Chromosome number is positively correlated with genome size, so rearrangement processes must include either insertion or deletion of DNA segments. We have conducted Fluorescence In Situ Hybridization (FISH) studies using 5S and 25S ribosomal DNA (rDNA) probes to survey for rearrangements, duplications, and phylogenetically-correlated variation within Paphiopedilum. We further studied sequence variation of the non-transcribed spacers of 5S rDNA (5S-NTS) to examine their complex duplication history, including the possibility that concerted evolutionary forces may homogenize diversity.\n\nResults: 5S and 25S rDNA loci among Paphiopedilum species, representing all key phylogenetic lineages, exhibit a considerable diversity that correlates well with recognized evolutionary groups. 25S rDNA signals range from 2 (representing 1 locus) to 9, the latter representing hemizygosity. 5S loci display extensive structural variation, and show from 2 specific signals to many, both major and minor and highly dispersed. The dispersed signals mainly occur at centromeric and subtelomeric positions, which are hotspots for chromosomal breakpoints.