Influence of decreasing nutrient path length on the development of engineered cartilage

SummaryObjectiveChondrocyte-seeded agarose constructs of 4mm diameter (2.34mm thickness) develop spatially inhomogeneous material properties with stiffer outer edges and a softer central core suggesting nutrient diffusion limitations to the central construct region [Guilak F, Sah RL, Setton LA. Physical regulation of cartilage metabolism. In: Mow VC, Hayes WC, Eds. Basic Orthopaedic Biomechanics, Philadelphia 1997;179–207.]. The effects of reducing construct thickness and creating channels running through the depth of the thick constructs were examined.MethodsIn Study 1, the properties of engineered cartilage of 0.78mm (thin) or 2.34mm (thick) thickness were compared. In Study 2, a single nutrient channel (1mm diameter) was created in the middle of each thick construct. In Study 3, the effects of channels on larger 10mm diameter, thick constructs were examined.ResultsThin constructs developed superior mechanical and biochemical properties than thick constructs. The channeled constructs developed significantly higher mechanical properties vs control channel-free constructs while exhibiting similar glycosaminoglycan (GAG) and collagen content. Collagen staining suggested that channels resulted in a more uniform fibrillar network. Improvements in constructs of 10mm diameter were similarly observed.ConclusionsThis study demonstrated that more homogeneous tissue-engineered cartilage constructs with improved mechanical properties can be achieved by reducing their thickness or incorporating macroscopic nutrient channels. Our data further suggests that these macroscopic channels remain open long enough to promote this enhanced tissue development while exhibiting the potential to refill with cell elaborated matrix with additional culture time. Together with reports that <3mm defects in cartilage heal in vivo and that irregular holes are associated with clinically used osteochondral graft procedures, we anticipate that a strategy of incorporating macroscopic channels may aid the development of clinically relevant engineered cartilage with functional properties

Comparative chromosome painting discloses homologous Segments in distantly related mammals

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species

Transport in Coupled Quantum Dots: Kondo Effect Versus Anti-Ferromagnetic Correlation

The interplay between the Kondo effect and the inter-dot magnetic interaction in a coupled-dot system is studied. An exact result for the transport properties at zero temperature is obtained by diagonalizing a cluster, composed by the double-dot and its vicinity, which is connected to leads. It is shown that the system goes continuously from the Kondo regime to an anti-ferromagnetic state as the inter-dot interaction is increased. The conductance, the charge at the dots and the spin-spin correlation are obtained as a function of the gate potential.Comment: 4 pages, 3 postscript figures. Submitted to PR

An Electrochemical Sensor Based on Nanostructured Hollandite-type Manganese Oxide for Detection of Potassium Ions

The participation of cations in redox reactions of manganese oxides provides an opportunity for development of chemical sensors for non-electroactive ions. A sensor based on a nanostructured hollandite-type manganese oxide was investigated for voltammetric detection of potassium ions. The detection is based on the measurement of anodic current generated by oxidation of Mn(III) to Mn(IV) at the surface of the electrode and the subsequent extraction of the potassium ions into the hollandite structure. In this work, an amperometric procedure at an operating potential of 0.80 V (versus SCE) is exploited for amperometric monitoring. The current signals are linearly proportional to potassium ion concentration in the range 4.97 × 10−5 to 9.05 × 10−4 mol L−1, with a correlation coefficient of 0.9997

Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment

SummaryCohesin is a conserved ring-shaped multiprotein complex that participates in chromosome segregation, DNA repair, and transcriptional regulation [1, 2]. Cohesin loading onto chromosomes universally requires the Scc2/4 “loader” complex (also called NippedBL/Mau2), mutations in which cause the developmental disorder Cornelia de Lange syndrome in humans [1–9]. Cohesin is most concentrated in the pericentromere, the region surrounding the centromere [10–15]. Enriched pericentromeric cohesin requires the Ctf19 kinetochore subcomplex in budding yeast [16–18]. Here, we uncover the spatial and temporal determinants for Scc2/4 centromere association. We demonstrate that the critical role of the Ctf19 complex is to enable Scc2/4 association with centromeres, through which cohesin loads and spreads onto the adjacent pericentromere. We show that, unexpectedly, Scc2 association with centromeres depends on cohesin itself. The absence of the Scc1/Mcd1/Rad21 cohesin subunit precludes Scc2 association with centromeres from anaphase until late G1. Expression of SCC1 is both necessary and sufficient for the binding of cohesin to its loader, the association of Scc2 with centromeres, and cohesin loading. We propose that cohesin triggers its own loading by enabling Scc2/4 to connect with chromosomal landmarks, which at centromeres are specified by the Ctf19 complex. Overall, our findings provide a paradigm for the spatial and temporal control of cohesin loading

Theory and Applications of Non-Relativistic and Relativistic Turbulent Reconnection

Realistic astrophysical environments are turbulent due to the extremely high Reynolds numbers. Therefore, the theories of reconnection intended for describing astrophysical reconnection should not ignore the effects of turbulence on magnetic reconnection. Turbulence is known to change the nature of many physical processes dramatically and in this review we claim that magnetic reconnection is not an exception. We stress that not only astrophysical turbulence is ubiquitous, but also magnetic reconnection itself induces turbulence. Thus turbulence must be accounted for in any realistic astrophysical reconnection setup. We argue that due to the similarities of MHD turbulence in relativistic and non-relativistic cases the theory of magnetic reconnection developed for the non-relativistic case can be extended to the relativistic case and we provide numerical simulations that support this conjecture. We also provide quantitative comparisons of the theoretical predictions and results of numerical experiments, including the situations when turbulent reconnection is self-driven, i.e. the turbulence in the system is generated by the reconnection process itself. We show how turbulent reconnection entails the violation of magnetic flux freezing, the conclusion that has really far reaching consequences for many realistically turbulent astrophysical environments. In addition, we consider observational testing of turbulent reconnection as well as numerous implications of the theory. The former includes the Sun and solar wind reconnection, while the latter include the process of reconnection diffusion induced by turbulent reconnection, the acceleration of energetic particles, bursts of turbulent reconnection related to black hole sources as well as gamma ray bursts. Finally, we explain why turbulent reconnection cannot be explained by turbulent resistivity or derived through the mean field approach.Comment: 66 pages, 24 figures, a chapter of the book "Magnetic Reconnection - Concepts and Applications", editors W. Gonzalez, E. N. Parke

Mediation role of cardiorespiratory fitness on the association between fatness and cardiometabolic risk in European adolescents: The HELENA study

Purpose: This study was aimed to analyze the mediation role of cardiorespiratory fitness (CRF) on the association between fatness and cardiometa-bolic risk scores (CMRs) in European adolescents. Methods: A cross-sectional study was conducted in adolescents (n = 525; 46% boys; 14.1 +/- 1.1 years old, mean +/- SD) from 10 European cities involved in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. CRF was measured by means of the shuttle run test, while fatness measures included body mass index (BMI), waist to height ratio, and fat mass index estimated from skinfold thicknesses. A clustered CMRs was computed by summing the standardized values of homeostasis model assessment, systolic blood pressure, triglycerides, total cholesterol/high-density lipoprotein cholesterol ratio, and leptin. Results: Linear regression models indicated that CRF acted as an important and partial mediator in the association between fatness and CMRs in 12-17-year-old adolescents (for BMI: coefficients of the indirect role beta = 0.058 (95% confidence interval (95%CI): 0.023-0.101), Sobel test z = 3.11 (10.0% mediation); for waist to height ratio: beta = 4.279 (95%CI: 2.242-7.059), z = 3.86 (11.5% mediation); and for fat mass index: beta = 0.060 (95%CI: 0.020-0.106), z = 2.85 (9.4% mediation); all p < 0.01). Conclusion: In adolescents, the association between fatness and CMRs could be partially decreased with improvements to fitness levels; therefore, CRF contribution both in the clinical field and public health could be important to consider and promote in adolescents independently of their fatness levels.We thank the adolescents who participated in the study and their parents and teachers for their collaboration. We also acknowledge the HELENA study members involved in fieldwork for their efforts. The HELENA project was supported by the European Community 6th Framework Programme for Research and Technological Development (contract FOODCT-2005-007034). The data for this study were gathered under the aegis of the HELENA project, and further analysis was additionally supported by the Spanish Ministry of Economy and Competitiveness (Grants RYC-2010-05957 and RYC-2011-09011), the Spanish Ministry of Health: Maternal, Child Health and Development Network (Grants RD08/0072 and RD16/0022), the Fondo Europeo de Desarrollo Regional (MICINN-FEDER), and the University of Granada, Plan Propio de Investigaci~on 2016, Excellence Actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). The content of this article reflects the authors' views alone, and the European Community is not liable for any use that may be made of the information contained herein

Early‐onset coenzyme Q10 deficiency associated with ataxia and respiratory chain dysfunction due to novel pathogenic COQ8A variants, including a large intragenic deletion

Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous subtype of mitochondrial disease. We report two girls with ataxia and mitochondrial respiratory chain deficiency who were shown to have primary CoQ10 deficiency. Muscle histochemistry displayed signs of mitochondrial dysfunction—ragged red fibers, mitochondrial paracrystalline inclusions, and lipid deposits while biochemical analyses revealed complex II+III respiratory chain deficiencies. MRI brain demonstrated cerebral and cerebellar atrophy. Targeted molecular analysis identified a homozygous c.1015G>A, p.(Ala339Thr) COQ8A variant in subject 1, while subject 2 was found to harbor a single heterozygous c.1029_1030delinsCA variant predicting a p.Gln343_Val344delinsHisMet amino acid substitution. Subsequent investigations identified a large‐scale COQ8A deletion in trans to the c.1029_1030delinsCA allele. A skin biopsy facilitated cDNA studies that confirmed exon skipping in the fibroblast derived COQ8A mRNA transcript. This report expands the molecular genetic spectrum associated with COQ8A ‐related mitochondrial disease and highlights the importance of thorough investigation of candidate pathogenic variants to establish phase. Rapid diagnosis is of the utmost importance as patients may benefit from therapeutic CoQ10 supplementation