847 research outputs found
IKKα modulates oxidative stress-induced DNA damage and repair in primary human OA chondrocytes
Impact of a reduced dose intensity of adjuvant anthracycline based chemotherapy in a population-based cohort of stage I–II breast cancers
Cardiac Resynchronization Therapy for End-Stage Hypertrophic Cardiomyopathy: The Need for Disease-Specific Criteria
Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C
Cardiac myosin binding protein-C (cMyBP-C) is a multi-domain (C0-C10) protein that regulates heart muscle contraction through interaction with myosin, actin and other sarcomeric proteins. Several mutations of this protein cause familial hypertrophic cardiomyopathy (HCM). Domain C1 of cMyBP-C plays a central role in protein interactions with actin and myosin. Here, we studied structure-function relationship of three disease causing mutations, Arg177His, Ala216Thr and Glu258Lys of the domain C1 using computational biology techniques with its available X-ray crystal structure. The results suggest that each mutation could affect structural properties of the domain C1, and hence it's structural integrity through modifying intra-molecular arrangements in a distinct mode. The mutations also change surface charge distributions, which could impact the binding of C1 with other sarcomeric proteins thereby affecting contractile function. These structural consequences of the C1 mutants could be valuable to understand the molecular mechanisms for the disease
Impact of cardiovascular involvement on the clinical course of paediatric mitochondrial disorders
Good subjective outcomes, stable knee and high return to sport after tibial eminence avulsion fracture in children
Avulsion fracture of the tibial spine (TSA) is uncommon in children, although its incidence is increasing with the earlier practice of competitive sport activities. This study aims to report mid to long term outcomes in children who sustained a TSA, with a special focus on a return to sport activities. Skeletally immature patients with a TSA, treated in two orthopedic hospitals, were evaluated for range of motion and knee laxity using KT1000, KiRA and Rolimeter. The pediatric International Knee Documentation Committee score (Pedi-IKDC) and the Hospital for Special Surgery pediatric Functional Activity Brief Scale (Pedi-FABS) questionnaires were recorded during the latest visit. Forty-two children were included. Twenty-six were treated nonoperatively and 16 underwent surgery. At a mean follow-up of 6.9 ± 3.6 years, 36 patients completed the questionnaires and 23 patients were tested with arthrometers. Among them, 96% had normal knee laxity. The Pedi-IKDC score averaged 96.4 ± 5.7 points, while the mean Pedi-FABS was 22.2 ± 5.9 points, without statistically significant differences between groups. Twenty-eight patients (78%) returned to their previous level of sport activity (eight amateur, 13 competitive, seven elite athletes). Eight patients (22%) quit sport, mostly because of re-injury fear. If properly treated, pediatric TSAs achieve a high rate of successful healing, with complete restoration of knee stability and an early return to sport activities
Basal and IL-1β enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKα and IKKβ NF-κB activating kinases
IKKα and IKKβ are essential kinases for activating NF-κB transcription factors that regulate cellular differentiation and inflammation. By virtue of their small size, chemokines support the crosstalk between cartilage and other joint compartments and contribute to immune cell chemotaxis in osteoarthritis (OA). Here we employed shRNA retroviruses to stably and efficiently ablate the expression of each IKK in primary OA chondrocytes to determine their individual contributions for monocyte chemotaxis in response to chondrocyte conditioned media. Both IKKα and IKKβ KDs blunted both the monocyte chemotactic potential and the protein levels of CCL2/MCP-1, the chemokine with the highest concentration and the strongest association with monocyte chemotaxis. These findings were mirrored by gene expression analysis indicating that the lowest levels of CCL2/MCP-1 and other monocyte-active chemokines were in IKKαKD cells under both basal and IL-1β stimulated conditions. We find that in their response to IL-1β stimulation IKKαKD primary OA chondrocytes have reduced levels of phosphorylated NFkappaB p65pSer536 and H3pSer10. Confocal microscopy analysis revealed co-localized p65 and H3pSer10 nuclear signals in agreement with our findings that IKKαKD effectively blunts their basal level and IL-1β dependent increases. Our results suggest that IKKα could be a novel OA disease target
Insect-based aquafeeds modulate the fatty acid profile of zebrafish: a comparison on the different life stages
Insects are considered as an alternative and sustainable ingredient for feed production. In this study, Hermetia illucens (Hi) prepupae (fed on coffee roasted by-product added with 10% Schyzochytrium sp., a marine protist rich in polyunsaturated fatty acids) was processed into meal and included at graded levels in five experimental diets to replace dietary fish meal (0, 25, 50, 75, 100%) offered to zebrafish (Danio rerio) as experimental model. The fatty acids (FAs) profile of fish larvae (20 days), juveniles (2 months, deprived of the viscera) and adults (6 months, male and female, deprived of the viscera) specimens was investigated to evaluate the impact of dietary FM replacement with full-fat Hi prepupae meal. For the first time, the quantification of FAs in Danio rerio, performed by gas chromatography-mass spectrometry, was computed in absolute terms (mg 100g-1 dw), identifying the real variation in the content of any single FA. In fish, quantified total FAs in larvae, juvenile, adult male and adult female were 134±2, 235±8, 266±3 and 266±8 mg g-1 dw, respectively. With respect to zebrafish fed the control diet, specimens fed diet with increasing level of Hi prepupae meal showed significantly higher content of saturated and omega6 FAs, and significantly lower content of poly-unsaturated and omega3 FAs, reflecting partially the FAs composition of the administered diets. At the same time, the docosahexaenoic/eicosapentaenoic acid ratio increased significantly. Moreover, adult female showed a higher content of PUFA with respect to adult male, which could be justified by the needs of physiological reproductive processes. The principal component analysis demonstrated that the FAs composition in Danio rerio depends on both the life stage and the diet
Second-harmonic generation sensitivity to transmembrane potential in normal and tumor cells.
Second-harmonic generation (SHG) is emerging as a powerful tool for the optical measurement of transmembrane potential in live cells with high sensitivity and temporal resolution. Using a patch clamp, we characterize the sensitivity of the SHG signal to transmembrane potential for the RH 237 dye in various normal and tumor cell types. SHG sensitivity shows a significant dependence on the type of cell, ranging from 10 to 17% per 100 mV. Furthermore, in the samples studied, tumor cell lines display a higher sensitivity compared to normal cells. In particular, the SHG sensitivity increases in the cell line Balb/c3T3 by the transformation induced with SV40 infection of the cells. We also demonstrate that fluorescent labeling of the membrane with RH 237 at the concentration used for SHG measurements does not induce any measurable alteration in the electrophysiological properties of the cells investigated. Therefore, SHG is suitable for the investigation of outstanding questions in electrophysiology and neurobiology
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