The evolutionary history of α-satellite DNA, the major component of primate centromeres, is hardly defined because of the difficulty in its sequence assembly and its rapid evolution when compared ...with most genomic sequences. By using several approaches, we have cloned, sequenced, and characterized α-satellite sequences from two species representing critical nodes in the primate phylogeny: the white-cheeked gibbon, a lesser ape, and marmoset, a New World monkey. Sequence analyses demonstrate that white-cheeked gibbon and marmoset α-satellite sequences are formed by units of ∼171 and ∼342 bp, respectively, and they both lack the high-order structure found in humans and great apes. Fluorescent in situ hybridization characterization shows a broad dispersal of α-satellite in the white-cheeked gibbon genome including centromeric, telomeric, and chromosomal interstitial localizations. On the other hand, centromeres in marmoset appear organized in highly divergent dimers roughly of 342 bp that show a similarity between monomers much lower than previously reported dimers, thus representing an ancient dimeric structure.
All these data shed light on the evolution of the centromeric sequences in Primates. Our results suggest radical differences in the structure, organization, and evolution of α-satellite DNA among different primate species, supporting the notion that 1) all the centromeric sequence in Primates evolved by genomic amplification, unequal crossover, and sequence homogenization using a 171 bp monomer as the basic seeding unit and 2) centromeric function is linked to relatively short repeated elements, more than higher-order structure.
Moreover, our data indicate that complex higher-order repeat structures are a peculiarity of the hominid lineage, showing the more complex organization in humans.
Chemical analysis of ancient residues of pharmaceutical or cosmetic preparations such as balms or ointments is made problematic by the high complexity of these mixtures, composed of organic and ...inorganic materials. Consequently, a multi-analytical approach and special caution in the interpretation of the results are necessary. In order to contribute to the improvement of analytical strategies for the characterization of complex residues and to reconstruct ancient medical practices, a replica of a pharmaceutical formulation of the seventeenth century was prepared in the laboratory according to a historically documented recipe. In a round robin exercise, a portion of the preparation was analysed as a blind sample by 11 laboratories using various analytical techniques. These included spectroscopic, chromatographic and mass spectrometric methods. None of the laboratories was able to completely reconstruct the complex formulation, but each of them gave partial positive results. The round robin exercise has demonstrated that the application of a multi-analytical approach can permit a complete and reliable reconstruction of the composition. Finally, on the basis of the results, an analytical protocol for the study of residues of ancient medical and pharmaceutical preparations has been outlined.
Low-grade intestinal inflammation and alterations of gut barrier integrity are found in patients affected by extraintestinal autoimmune diseases such as type 1 diabetes (T1D), but a direct causal ...link between enteropathy and triggering of autoimmunity is yet to be established. Here, we found that onset of autoimmunity in preclinical models of T1D is associated with alterations of the mucus layer structure and loss of gut barrier integrity. Importantly, we showed that breakage of the gut barrier integrity in BDC2.5XNOD mice carrying a transgenic T cell receptor (TCR) specific for a beta cell autoantigen leads to activation of islet-reactive T cells within the gut mucosa and onset of T1D. The intestinal activation of islet-reactive T cells requires the presence of gut microbiota and is abolished when mice are depleted of endogenous commensal microbiota by antibiotic treatment. Our results indicate that loss of gut barrier continuity can lead to activation of islet-specific T cells within the intestinal mucosa and to autoimmune diabetes and provide a strong rationale to design innovative therapeutic interventions in “at-risk” individuals aimed at restoring gut barrier integrity to prevent T1D occurrence.
Background
Distal humeral malunions are uncommon injuries, often associated with limited elbow motion, pain, instability, weakness, and sometimes ulnar neuritis. The complex anatomy of the elbow ...joint makes this condition one of the most complex elbow injuries to treat.
Materials and methods
Four patients were treated by the same surgeon between 2011 and 2013 using a double-locking precontoured plating system for malunited intra-articular or extra-articular fractures of the distal end of the humerus.
Results
At a mean 3 years of follow-up, a significant improvement in the elbow motion and functional outcome, evaluated with the Mayo Elbow Performance Index and the Disability of the Arm, Shoulder, and Hand, were observed. Articular reduction obtained after the surgery was maintained in all patients without evidence of avascular necrosis. No other complications (i.e., infection, nervous iatrogenic lesions) were reported.
Conclusions
Corrective osteotomy using double-locking precontoured plating system preceded by preoperative planning using a CT scan allowed an improvement in the functional outcome and elbow motion, without complications.
Objectives: Mechanical Circulatory Support (MCS) systems are characterized by a constant flow of innovations. The use of mock loops could speed up the validation process of MCS. However, they usually ...offer realistic representations of ventricular hemodynamics, but not of its anatomy, limiting their testing capabilities. We propose an innovative cardiovascular simulator that includes a physiologically activated 3D model of the left ventricle (LV), suitable to test MCSs under different (patho-)physiological conditions. Methods: The cardiovascular simulator includes an in silico lumped parameters model of the cardiovascular system (right ventricle, atria, pulmonary and systemic circulations). The in vitro system consists of a compliant 3D model of the LV, hydraulically activated by gear pumps and DC motors to recreate pressure-volume (PV) loops following the loading conditions resulting from the in-silico model. Starting from the CT scan of a patient, the compliant 3D LV was created in polyvinyl alcohol using the molding technique (inner chamber volume 125 mL). At first the hemodynamic of a healthy patient with a cardiac output of 5.0 L/min was simulated. Then afterloads, preloads, heart rates and ventricular contractile states were changed, to mimic different heart failure conditions. Results: The PV loops measured in the 3D LV model range between the systolic and diastolic values of the cardiac cycle for each considered case scenario. PV loops reflect the changes in the afterload and/or preload applied in the in-silico model and the intrinsic mechanical properties of the considered LV. Conclusions: The proposed cardiovascular simulator represents a realistic anatomical and physiological replication of the LV interacting with the remainder closed loop circulatory in silico model. The result is a 4D LV model that can work as a reliable test bench for MCSs under different (patho-)physiological conditions. Acknowledgements: This study was supported by an FWO project (1SD0321N) and a KU Leuven C3 project (C3/20/033).
Myxoid Liposarcomas (MLS), characterized by the expression of FUS‐CHOP fusion gene are clinically very sensitive to the DNA binding antitumor agent, trabectedin. However, resistance eventually ...occurs, preventing disease eradication. To investigate the mechanisms of resistance, a trabectedin resistant cell line, 402‐91/ET, was developed. The resistance to trabectedin was not related to the expression of MDR related proteins, uptake/efflux of trabectedin or GSH levels that were similar in parental and resistant cells. The 402‐91/ET cells were hypersensitive to UV light because of a nucleotide excision repair defect: XPG complementation decreased sensitivity to UV rays, but only partially to trabectedin. 402‐91/ET cells showed collateral sensitivity to temozolomide due to the lack of O6‐methylguanine‐DNA‐methyltransferase (MGMT) activity, related to the hypermethylation of MGMT promoter. In 402‐91 cells chromatin immunoprecipitation (ChIP) assays showed that FUS‐CHOP was bound to the PTX3 and FN1 gene promoters, as previously described, and trabectedin caused FUS‐CHOP detachment from DNA. Here we report that, in contrast, in 402‐91/ET cells, FUS‐CHOP was not bound to these promoters. Differences in the modulation of transcription of genes involved in different pathways including signal transduction, apoptosis and stress response between the two cell lines were found. Trabectedin activates the transcription of genes involved in the adipogenic‐program such as c/EBPα and β, in 402‐91 but not in 402‐91/ET cell lines. The collateral sensitivity of 402‐91/ET to temozolomide provides the rationale to investigate the potential use of methylating agents in MLS patients resistant to trabectedin.
An 11-year-old female spayed domestic shorthair cat was presented with haematuria of 2 months’ duration followed by pollakiuria and stranguria. A firm, non-painful mass in the urinary bladder was ...palpated. Abdominal radiographs and ultrasound were suggestive of a urinary neoplasia. During explorative laparotomy, a partial cystectomy and surgical debulking were performed. Histopathology and immunostaining were consistent with a fibrosarcoma. The cat was discharged 10 days after surgery with a residual mass of about 1.8 cm on ultrasound re-examination. The cat was not given adjuvant therapy. The cat was euthanased 8 months after surgery because of tumour invasion of the urinary trigone and subsequent ureter dilation, hydronephrosis and severe azotaemia. Malignant urinary fibrosarcoma in this cat appeared to be only locally invasive. Palliative surgery without adjuvant postoperative chemotherapy in this cat resulted in an 8 month period of good quality of life.
The use of ceramic-on-ceramic (alumina- and zirconia-based) couplings in hip joint prostheses has been reported to produce lower wear rates than other combinations (i.e., metal-on-polyethylene and ...ceramic-on-polyethylene). The addition of zirconia into an alumina matrix (zirconia-toughened alumina, ZTA) has been reported to result in an enhancement of flexural strength, fracture toughness, and fatigue resistance. The development of new processing routes in nonaqueous media has allowed to obtain high-density ZTA nanocomposites with a very homogeneous microstructure and a significantly smaller and narrower particle-size distribution of zirconia than conventional powder mixing methods. The aim of the present study was to set up and validate a new ZTA nanocomposite by testing its biocompatibility and wear behavior in a hip-joint simulator in comparison with commercial alumina and experimental alumina specimens. The primary osteoblast proliferation onto ZTA nanocomposite samples was found to be not significantly different from that onto commercial alumina samples. After 7 million cycles, no significant differences were observed between the wear behaviors of the three sets of cups. In this light, it can be affirmed that ZTA nanocomposite materials can offer the option of improving the lifetime and reliability of ceramic joint prostheses.
Since the first report in 1993, an ectopic centromere, i.e. neocentromere formation, has been reported in more than 100 small supernumerary marker chromosomes (sSMC), in 7 instances of centromere ...repositioning, and in about a dozen cases with more complex chromosomal rearrangements. Here we report 2 new cases with centromere repositioning and 3 neocentric sSMC consisting exclusively of heterochromatic material. Yet, no centromere formation was reported for the regions 18q22.1 and Xq27.1∼27.2 as it was observed in the 2 cases with centromere repositioning here; in both cases, cytogenetically an inversion was suggested. Two of the 3 neocentric sSMC were derived from a short arm of an acrocentric chromosome. The remainder neocentric sSMC case was previously reported and was stainable only by material derived from itself.
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