Selfish supernumerary chromosome reveals its origin as a mosaic of host genome and organellar sequences

Supernumerary B chromosomes are optional additions to the basic set of A chromosomes, and occur in all eukaryotic groups. They differ from the basic complement in morphology, pairing behavior, and inheritance and are not required for normal growth and development. The current view is that B chromosomes are parasitic elements comparable to selfish DNA, like transposons. In contrast to transposons, they are autonomously inherited independent of the host genome and have their own mechanisms of mitotic or meiotic drive. Although B chromosomes were first described a century ago, little is known about their origin and molecular makeup. The widely accepted view is that they are derived from fragments of A chromosomes and/or generated in response to interspecific hybridization. Through next-generation sequencing of sorted A and B chromosomes, we show that B chromosomes of rye are rich in gene-derived sequences, allowing us to trace their origin to fragments of A chromosomes, with the largest parts corresponding to rye chromosomes 3R and 7R. Compared with A chromosomes, B chromosomes were also found to accumulate large amounts of specific repeats and insertions of organellar DNA. The origin of rye B chromosomes occurred an estimated ～1.1-1.3 Mya, overlapping in time with the onset of the genus Secale (1.7 Mya). We propose a comprehensive model of B chromosome evolution, including its origin by recombination of several A chromosomes followed by capturing of additional A-derived and organellar sequences and amplification of B-specific repeats.     

The effects of repeated delivery of angiotensin II AT(1) receptor antisense on distinct vasoactive systems in Ren-2 transgenic rats: young vs. adult animals

Although Ren-2 transgenic rat (TGR) is defined as a model of angiotensin II-dependent hypertension, we studied whether the renin-angiotensin system (RAS) is really the main contributor to blood pressure (BP) elevation in hetero- and homozygous TGRs. Moreover, we examined whether repeated antisense (AS) therapy against AT(1) receptors would have a similar effect on the BP and the contribution of the principle vasoconstrictor/vasodilator systems to BP regulation in young and adult TGRs. From the age of 30 (young) and 100 (adult) days, rats were injected with AS for 40 days in 10-day intervals. After 10 and 40 days of AS therapy, the basal BP and acute BP responses to the sequential blockade of the RAS, sympathetic nervous (SNS) and nitric oxide systems were determined in conscious rats. The RAS system was the major system maintaining elevated BP in young homozygous animals, whereas there was an increasing contribution of the SNS in heterozygous TGR with age. The AS therapy in the young TGR had a transient BP-lowering effect that was associated with reduced cardiac hypertrophy; the AS therapy was most effective in young homozygous TGR, causing a substantial reduction of angiotensin-dependent vasoconstriction. In heterozygous rats, AS therapy at earlier stages was related to an inhibition of sympathetic vasoconstriction, whereas to RAS inhibition in established hypertension. In conclusion, repeated AS therapy had transient antihypertensive effects exclusively in young TGR. The contribution of the RAS to BP maintenance is highly important only in homozygous TGRs, whereas it is surpassed by SNS in heterozygous TGR.     

Profile of thrombin generation in children with acute lymphoblastic leukemia treated by Berlin-Frankfurt-Münster (BFM) protocols

Treatment with L-asparaginase is associated with coagulation disturbances with deep venous thrombosis being the most common clinical consequence. Use of the calibrated automated thrombogram allows precise estimation of thrombin generated in vitro. We show the first data on thrombin generation, measured by calibrated automated thrombography (CAT), in children with acute lymphoblastic leukemia treated with L-asparaginase. Thrombin generation was measured by means of CAT in 23 children treated for acute lymphoblastic leukemia. Samples were obtained at predefined time points during the induction and reinduction phase of acute lymphoblastic leukemia-intercontinental Berlin-Frankfurt-Münster (BFM) 2000 or Associazione Italiana Ematologica Oncologia Pedaitrica Interim BFM 2000 protocols. Antihrombin and fibrinogen were measured on the same sample. Twenty-eight sets of thrombin generation measurements were collected from 23 patients. We observed no significant effect of antithrombin deficiency and/or hypofibrinogenemia on thrombin generation. Endogenous thrombin generation and peak thrombin were significantly higher during induction than in the reinduction phase (P?相似文献   

C‐type natriuretic peptide slows down wound healing but promotes angiogenesis in SKH1‐hr hairless mice

C‐type natriuretic peptide (CNP) is known to increase growth rate of endothelial cells in vitro. In addition, gene transfer of CNP into ischaemic muscle was shown to induce angiogenesis. So far, no study has addressed the effect of CNP on dermal wound healing. The ear wound model in mice was used in this study. The first group was treated with dsRed‐CNP plasmid, whereas the second group was transfected with the empty dsRed‐sine plasmid, lacking sequence coding for CNP. The third group was sham operated and treated with saline to serve as second control. Wound size was measured on days 0, 1, 3, 5, 7, 9, 11 and 14. On days 7 and 14 capillary density was analysed. Wound closure rate was significantly reduced in mice treated with CNP [dsRed‐CNP 73·3 ± 3·2% versus dsRed‐sine 94·5 ± 2·4% versus saline 92·1 ± 2·4%, n = 8 per group, analysis of variance (ANOVA) P < 0·001] at day 7 postop. Capillary density was found to be significantly higher in CNP‐treated mice (dsRed‐CNP 18·7 ± 3·9 versus dsRed‐sine 12·3 ± 2·7 versus control 10·1 ± 4·7, CD31⁺ capillaries per microscope field, ANOVA P = 0·018) at day 14 postoperative. CNP significantly reduces wound closure rate in hairless mice but promotes the development of new blood vessels. A possible explanation is the dual effect of CNP, inhibiting growth of fibromyoblasts but stimulating growth of endothelial cells. Thus, CNP may serve as a therapeutic approach to diseases caused by hyperfibrosis.     

Social participation in early and established rheumatoid arthritis patients

Purpose: The aim of the study was to examine whether rheumatoid arthritis (RA) patients with different levels of restriction in social participation differ in disease related as well as psychosocial variables and whether a similar pattern can be found among early and established RA patients.

Method: Two samples of RA patients with early (n?=?97; age?=?53?±?12.3 years; disease duration?= 2.8?±?1.2 years; 76% women) and established (n?=?143; age?=?58?±?10.3 years; disease duration?= 16.1?±?3.6 years; 86% women) were collected. The pattern of differences for the patients with different level of participation restriction (no restriction, mild, moderate or high restriction) was explored by the Jonckheere–Terpstra test. Results: Significant differences were found between patients with different levels of social participation restrictions in both samples in pain, fatigue, functional disability, anxiety, depression and mastery. Generally, it was found that patients with higher restrictions experienced more pain and fatigue, more anxiety and depression and reported lower mastery. Similar pattern of differences concerning disease activity and self-esteem was found mainly in the established group. Conclusions: The study shows that the level of perceived restrictions in social participation are highly relevant regarding the disease related variables such as pain, fatigue and functional disability as well as psychological status and personal resources in both early and established RA.

• Implications for Rehabilitation

• Supporting involvement and participation of individuals with rheumatoid arthritis is important for decreasing the impact of RA symptoms on everyday life.

• Recognition and empowerment of individual resources such a mastery and self-esteem of RA patients could be beneficial for overcoming restrictions in participation.

     

Molecular cytogenetic analysis of complex karyotypes with derivative chromosome der(1)t(1;5) found in two patients with myeloid leukemia

Dedifferentiated liposarcoma of the pleura is an extremely rare malignancy mimicking a variety of tumors, such as other sarcomas, mesothelioma, and malignant solitary fibrous tumor of the pleura. Liposarcoma of the pleura can be combined with mediastinal involvement, and in most cases it may be impossible to be certain where the primary tumor originated. In this report, we describe a very rare occurence of a dedifferentiated liposarcoma of the pleura in a 76-year-old woman associated with a distinct second dedifferentiated liposarcoma of the mediastinum. Histologically, the pleural tumor demonstrated spindle cells arranged in a fascicular pattern, whereas the mediastinal tumor was mostly adipocytic with small areas of spindle cells. Vimentin and protein S100 were focally expressed by the tumor cells. The differential diagnosis of the pleural mass included malignant solitary fibrous tumor. Cytogenetic analysis showed supernumerary ring chromosomes in the pleural tumor, as well as strong amplification of MDM2 and CDK4 genes in both tumors. Array comparative genomic hybridization showed amplifications of chromosome arms 6q, 12q, and 15q, shared by both tumors and strongly pointing to a common origin.     

Phase Composition of Al-Si Coating from the Initial State to the Hot-Stamped Condition

The chemical and phase composition of the coating and the coating/substrate interface of an Al-Si-coated 22MnB5 hot stamped steel was investigated by means of SEM-EDS, XRD, micro-XRD and electron diffraction. Moreover, the surface profile was analyzed by XPS and roughness measurements. The XPS measurements showed that the thickness of the Si and Al oxide layers increased from 14 to 76 nm after die-quenching, and that the surface roughness increased as well as a result of volume changes caused by phase transformations. In addition to the FeAl(Si) and Fe₂Al₅ phases and the interdiffusion layer forming complex structures in the coating, electron diffraction confirmed the presence of an Fe₂Al₅ phase, and also revealed very thin layers of Fe₃(Al,Si)C, Fe₂(Al,Si)₅ and Al-bearing rod-shaped particles in the immediate vicinity of the steel interface. Moreover, the scattered nonuniform layer of the Fe₂Al₈Si phase was identified in the outermost layer of the coating. Despite numerous studies devoted to researching the phase composition of the Al-Si coating applied to hot stamped steel, electron diffraction revealed very thin layers and particles on the coating/substrate interface and outermost layer, which have not been analyzed in detail.     

Colon resection in elderly patients: comparison of data of a single surgical department with collective data from the Czech Republic

Colorectal cancer is predominantly a disease of elderly people, since over 70% of cases occur in those aged 65 years or older. Clinicians have to frequently decide whether major surgery is justified in elderly patients with a limited life expectancy. Our retrospective study was aimed to compare outcomes of primary surgery for colorectal cancer in the elderly patient population. The evaluated data were collected from the 1st Department of Surgery, Charles University, and from all over the Czech Republic. Patients were divided into three groups: the young-old (21-59 years), the older-old (60-69 years), and the oldest-old (>69 years) patients. In the collective data the youngest and the oldest groups differ significantly in the rate of early postoperative complications (12.3% versus 17.6%, p<0.001). The number of complications associated with the emergency procedures was twice as high compared to elective surgery in all groups (p<0.001). There was no correlation between age and length of hospital stay in the single surgery department. These data suggest that major oncology procedures may be undertaken in older patients in whom operative risk is reasonable, with acceptable rates of complications.     

A prospective,randomized trial of perioperative prophylactic cefamandole in elective colorectal surgery for malignancy

The impact on wound infection of the addition of perioperative cefamandole to a mechanical bowel preparation with oral antibiotics was studied in a prospective randomized series of patients undergoing elective colectomy for biopsy-proven carcinoma or adenomatous polyps. Seventy patients were randomized, all underwent mechanical bowel preparation and received oral neomycin and erythromycin base. Thirty-four patients also received a preoperative and four postoperative doses of cefamandole, while 36 patients were randomized to receive no parenteral antibiotics. The two groups were well stratified for age, sex, and risk factors. The Dukes stage was similar and the surgical procedures were equally distributed in the two groups. There were no wound infections in the 34 patients receiving cefamandole and only one wound infection (2.8 percent) in the 36 control patients. Therefore, the addition of perioperative intravenous cefamandole to a good mechanical bowel preparation with oral antibiotics was of no benefit in reducing wound infections following resection of colorectal malignancies in this select group of patients. Supported by the Eli Lilly Company.