Creatine kinase in energy metabolic signaling in muscle

There has been much debate on the mechanism of regulation of mitochondrial ATP synthesis to balance ATP consumption during changing cardiac workloads. A key role of creatine kinase (CK) isoenzymes in this regulation of oxidative phosphorylation and in intracellular energy transport had been proposed, but has in the mean time been disputed for many years. It was hypothesized that high-energy phosphoryl groups are obligatorily transferred via CK; this is termed the phosphocreatine shuttle. The other important role ascribed to the CK system is its ability to buffer ADP concentration in cytosol near sites of ATP hydrolysis. 

Almost all of the experiments to determine the role of CK had been done in the steady state, but recently the dynamic response of oxidative phosphorylation to quick changes in
cytosolic ATP hydrolysis has been assessed at various levels of inhibition of CK. Steady state models of CK function in energy transfer existed but were unable to explain the dynamic response with CK inhibited.

The aim of this study was to explain the mode of functioning of the CK system in heart, and in particular the role of different CK isoenzymes in the dynamic response to workload steps. For this purpose we used a mathematical model of cardiac muscle cell energy metabolism containing the kinetics of the key processes of energy production, consumption and transfer pathways. The model underscores that CK plays indeed a dual role in the cardiac cells. The buffering role of CK system is due to the activity of myofibrillar CK (MMCK) while the energy transfer role depends on the activity of mitochondrial CK (MiCK). We propose that this may lead to the differences in regulation mechanisms and energy transfer modes in species with relatively low MiCK activity such as rabbit in comparison with species with high MiCK activity such as rat.

The model needed modification to explain the new type of experimental data on the dynamic response of the mitochondria. We submit that building a Virtual Muscle Cell is not possible without continuous experimental tests to improve the model. In close interaction with experiments we are developing a model for muscle energy metabolism and transport mediated by the creatine kinase isoforms which now already can explain many different types of experiments

Bag-in-the-lens intraocular lens in paediatric cataract surgery: intraoperative and postoperative outcomes

Purpose: To report intra- and postoperative surgical outcome using the bag-in-the-lens (BIL) technique in paediatric cataract surgery. Methods: In a retrospective case series, we studied the outcomes of children aged <12 years operated for cataract with the bag-in-the-lens intraocular lens (IOL), with a minimum of 6 months of follow-up. Results: Since 2013, 50 eyes in 30 patients <12 years (20 bilateral and 10 unilateral) have been operated at our department with the BIL technique, with a median follow-up time of 33.5 months (range 6–77). Median age at surgery was 49.5 months (4–139). In one case, the IOL luxated through the capsulorhexes to the vitreous, but could be secured and repositioned as planned without further difficulties. Anterior vitrectomy was necessary in one case due to prolapse of vitreous to the anterior chamber during surgery. No other intraoperative complications occurred. Visual axis opacification (VAO) developed in four eyes (8%). So far, only one of these has needed a reoperation with clearing of the secondary cataract. A complete absence of VAO was thus seen throughout the study period in 92%. In two eyes, postoperative iris capture occurred. In both cases, surgical repositioning of the iris was needed. No eyes developed secondary glaucoma during the study period. Conclusion: The BIL technique seems to be a safe surgical procedure in paediatric cataract, with significantly less complications and need for additional surgery compared with the conventional lens-in-the-bag technique.publishedVersio

Sex-biased dispersal in a northern ungulate population

In most mammals dispersal is male-biased and in many polygynous ungulates female philopatry and matrilineal grouping involve small-scale genetic structure. We have through sex-related differences in microsatellite allele distribution addressed sex-biased dispersal in a spatially expanding northern ungulate population. The Norwegian red deer population (Cervus elaphus atlanticus) has the last hundred years grown substantially and expanded spatially after a major decline from 300 to 100 years ago. Previous Bayesian analyses suggest a present division of genetic variation into five geographically separated subpopulations. Among these subpopulations the overall Fst values were 0.067 (SE=0.014) for males and 0.094 (SE=0.017) for females. Pairwise Fst values were significantly higher for females than males, demonstrating a stronger genetic structure among females, and that dispersal has been lower in females than males. Accordingly, a higher number of male than female first generation dispersers were identified among the five subpopulations using Bayesian assignment with prior population information, but significantly so only with relaxed stringency levels of assignment. The identified male-biased dispersal distances varied from 30 to 300 kilometers suggesting male biased dispersal on a large scale in red deer

MtsslWizard: In Silico Spin-Labeling and Generation of Distance Distributions in PyMOL

MtsslWizard is a computer program, which operates as a plugin for the PyMOL molecular graphics system. MtsslWizard estimates distances between spin labels on proteins quickly with user-configurable options through a simple graphical interface. In default mode, the program searches for ensembles of possible MTSSL conformations that do not clash with a static model of the protein. Once conformations are assigned, distance distributions between two or more ensembles are calculated, displayed, and can be exported to other software. The program’s use is evaluated in a number of challenging test cases and its strengths and weaknesses evaluated. The benefits of the program are its accuracy and simplicity

Classification and unscrambling a class-inside-class situation by object target rotation : Hungarian silver coins of the Árpád Dynasty, 997 – 1301 AD

Classification is an important part of chemometrics and mostly based on optimization by vector rotations. The present study is a continuation of the classification of medieval Hungarian silver coins including the 16 kings of the Hungarian Árpád Dynasty (997AD – 1301AD) (Rácz et al.: Heritage Science 2013 1:2) The Rácz et al. paper identified three historical periods of the Árpád Dynasty from chemical data. The aim of the present study is to test whether the classification could be further refined by marker object projection aided classification. It offers an example of the efficiency of this method in unscrambling a classinside- class situation. The frequency distribution of concentrations of the coins are skewed and to a certain extent bi- modal, and the arithmetic mean value and standard deviation around the mean frequently used in parametric methods may be poor descriptors of the information carried by the data. We test a combination of principal components decomposition and the nonparametric, non-iterative object target rotation method to overcome some of the theoretical limitations of parametric methods. This test includes identification of archetypical class ―Ambassadors‖ of each of the three historical periods of the Árpád Dynasty and shows a class-inside-class situation

Fulcrum: Flexible Network Coding for Heterogeneous Devices

Producción CientíficaWe introduce Fulcrum, a network coding framework that achieves three seemingly conflicting objectives: 1) to reduce the coding coefficient overhead down to nearly n bits per packet in a generation of n packets; 2) to conduct the network coding using only Galois field GF(2) operations at intermediate nodes if necessary, dramatically reducing computing complexity in the network; and 3) to deliver an end-to-end performance that is close to that of a high-field network coding system for high-end receivers, while simultaneously catering to low-end receivers that decode in GF(2). As a consequence of 1) and 3), Fulcrum has a unique trait missing so far in the network coding literature: providing the network with the flexibility to distribute computational complexity over different devices depending on their current load, network conditions, or energy constraints. At the core of our framework lies the idea of precoding at the sources using an expansion field GF(2 h ), h > 1, to increase the number of dimensions seen by the network. Fulcrum can use any high-field linear code for precoding, e.g., Reed-Solomon or Random Linear Network Coding (RLNC). Our analysis shows that the number of additional dimensions created during precoding controls the trade-off between delay, overhead, and computing complexity. Our implementation and measurements show that Fulcrum achieves similar decoding probabilities as high field RLNC but with encoders and decoders that are an order of magnitude faster.Green Mobile Cloud project (grant DFF-0602-01372B)Colorcast project (grant DFF-0602-02661B)TuneSCode project (grant DFF - 1335-00125)Danish Council for Independent Research (grant DFF-4002-00367)Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (grants MTM2012-36917-C03-03 / MTM2015-65764-C3-2-P / MTM2015-69138-REDT)Agencia Estatal de Investigación - Fondo Social Europeo (grant RYC-2016-20208)Aarhus Universitets Forskningsfond Starting (grant AUFF-2017-FLS-7-1

Large' vs. 'small' players: a closer look at the dynamics of speculative attacks

What is the role of large players like hedge funds and other highly leveraged institutions in speculative attacks? In recent theoretical work, large players may induce an attack by an early move, providing information to smaller agents. In contrast, many observers argue that large players are in the rear. We propose a model that allows both the large player to move early in order to induce speculation by small players, or wait so as to benefit from a high interest rate prior to the attack. Using data on net positions of large (foreigners) and small (locals) players, we find that large players moved last in three attacks on the Norwegian krone (nok) during the 1990s: The ERM-crisis of 1992, the NOK-pressure in 1997, and after the Russian moratorium in 1998. In 1998 there was a contemporaneous attack on the Swedish krona (sek) in which large players moved early. Interest rates did not increase in Sweden so there was little to gain by a delayed attack

Differential in vivo tumorigenicity of distinct subpopulations from a luminal-like breast cancer xenograft

Intratumor heterogeneity caused by genetic, phenotypic or functional differences between cancer cell subpopulations is a considerable clinical challenge. Understanding subpopulation dynamics is therefore central for both optimization of existing therapy and for development of new treatment. The aim of this study was to isolate subpopulations from a primary tumor and by comparing molecular characteristics of these subpopulations, find explanations to their differing tumorigenicity. Cell subpopulations from two patient derived in vivo models of primary breast cancer, ER+ and ER-, were identified. EpCAM+ cells from the ER+ model gave rise to tumors independently of stroma cell support. The tumorigenic fraction was further divided based on SSEA-4 and CD24 expression. Both markers were expressed in ER+ breast cancer biopsies. FAC-sorted cells based on EpCAM, SSEA-4 and CD24 expression were subsequently tested for differences in functionality by in vivo tumorigenicity assay. Three out of four subpopulations of cells were tumorigenic and showed variable ability to recapitulate the marker expression of the original tumor. Whole genome expression analysis of the sorted populations disclosed high similarity in the transcriptional profiles between the tumorigenic populations. Comparing the non-tumorigenic vs the tumorigenic populations, 44 transcripts were, however, significantly differentially expressed. A subset of these, 26 identified and named genes, highly expressed in the non-tumorigenic population, predicted longer overall survival (N = 737, p<0.0001) and distant metastasis free survival (DMFS) (N = 1379, p<0.0001) when performing Kaplan-Meier survival analysis using the GOBO online database. The 26 gene set correlated with longer DMFS in multiple breast cancer subgroups. Copy number profiling revealed no aberrations that could explain the observed differences in tumorigenicity. This study emphasizes the functional variability among cell populations that are otherwise genomically similar, and that the risk of breast cancer recurrence can only be eliminated if the tumorigenic abilities in multiple cancer cell subpopulations are inhibited