bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stepwise approach for combining many sources of evidence for site-recognition in genomic sequences
Authors: Pérez-Rodríguez Javier , García-Pedrajas Nicolás 
Published: March 2016

Abstract
Background
Recognizing the different functional parts of genes, such as promoters, translation initiation sites, donors, acceptors and stop codons, is a fundamental task of many current studies in Bioinformatics. Currently, the most successful methods use powerful classifiers, such as support vector machines with various string kernels. However, with the rapid evolution of our ability to collect genomic information, it has been shown that combining many sources of evidence is fundamental to the success of any recognition task. With the advent of next-generation sequencing, the number of available genomes is increasing very rapidly. Thus, methods for making use of such large amounts of information are needed.

Results
In this paper, we present a methodology for combining tens or even hundreds of different classifiers for an improved performance. Our approach can include almost a limitless number of sources of evidence. We can use the evidence for the prediction of sites in a certain species, such as human, or other species as needed. This approach can be used for any of the functional recognition tasks cited above. However, to provide the necessary focus, we have tested our approach in two functional recognition tasks: translation initiation site and stop codon recognition. We have used the entire human genome as a target and another 20 species as sources of evidence and tested our method on five different human chromosomes. The proposed method achieves better accuracy than the best state-of-the-art method both in terms of the geometric mean of the specificity and sensitivity and the area under the receiver operating characteristic and precision recall curves. Furthermore, our approach shows a more principled way for selecting the best genomes to be combined for a given recognition task.

Conclusions
Our approach has proven to be a powerful tool for improving the performance of functional site recognition, and it is a useful method for combining many sources of evidence for any recognition task in Bioinformatics. The results also show that the common approach of heuristically choosing the species to be used as source of evidence can be improved because the best combinations of genomes for recognition were those not usually selected. Although the experiments were performed for translation initiation site and stop codon recognition, any other recognition task may benefit from our methodology.
Comparative study of equine mesenchymal stem cells from healthy and injured synovial tissues: an in vitro assessment
Authors: Fülber Joice , Maria Durvanei A. , Silva Luis Cláudio Lopes Correia da , Massoco Cristina O. , Agreste Fernanda , Baccarin Raquel Y. Arantes 
Published: March 2016

Abstract
Background
Bone marrow and adipose tissues are known sources of mesenchymal stem cells (MSCs) in horses; however, synovial tissues might be a promising alternative. The aim of this study was to evaluate phenotypic characteristics and differentiation potential of equine MSCs from synovial fluid (SF) and synovial membrane (SM) of healthy joints (SF-H and SM-H), joints with osteoarthritis (SF-OA and SM-OA) and joints with osteochondritis dissecans (SF-OCD and SM-OCD) to determine the most suitable synovial source for an allogeneic therapy cell bank.

Methods
Expression of the markers CD90, CD105, CD44, and CD34 in SF-H, SM-H, SF-OA, SM-OA, SF-OCD and SM-OCD was verified by flow cytometry, and expression of cytokeratin, vimentin, PGP 9.5, PCNA, lysozyme, nanog, and Oct4 was verified by immunocytochemistry. MSCs were cultured and evaluated for their chondrogenic, osteogenic and adipogenic differentiation potential. Final quantification of extracellular matrix and mineralized matrix was determined using AxioVision software. A tumorigenicity test was conducted in Balb-Cnu/nu mice to verify the safety of the MSCs from these sources.

Results
Cultured cells from SF and SM exhibited fibroblastoid morphology and the ability to adhere to plastic. The time elapsed between primary culture and the third passage was approximately 73 days for SF-H, 89 days for SF-OCD, 60 days for SF-OA, 68 days for SM-H, 57 days for SM-OCD and 54 days for SM-OA. The doubling time for SF-OCD was higher than that for other cells at the first passage (P < 0.05). MSCs from synovial tissues showed positive expression of the markers CD90, CD44, lysozyme, PGP 9.5, PCNA and vimentin and were able to differentiate into chondrogenic (21 days) and osteogenic (21 days) lineages, and, although poorly, into adipogenic lineages (14 days). The areas staining positive for extracellular matrix in the SF-H and SM-H groups were larger than those in the SF-OA and SM-OA groups (P < 0.05). The positive mineralized matrix area in the SF-H group was larger than those in all the other groups (P < 0.05). The studied cells exhibited no tumorigenic effects.

Conclusions
SF and SM are viable sources of equine MSCs. All sources studied provide suitable MSCs for an allogeneic therapy cell bank; nevertheless, MSCs from healthy joints may be preferable for cell banking purposes because they exhibit better chondrogenic differentiation capacity.
Dynamic internalization and recycling of a metal ion transporter: Cu homeostasis and CTR1, the human Cu+ uptake system
Authors: Clifford Rebecca J. , Maryon Edward B. , Kaplan Jack H. 
Published: March 2016

ABSTRACT
Cu ion (Cu) entry into human cells is mediated by CTR1 (also known as SLC31A1), the high-affinity Cu transporter. When extracellular Cu is raised, the cell is protected against excess accumulation by rapid internalization of the transporter. When Cu is lowered, the transporter returns to the membrane. We show in HEK293 cells overexpressing CTR1 that expression of either the C-terminal domain of AP180 (also known as SNAP91), a clathrin-coat assembly protein that sequesters clathrin, or a dominant-negative mutant of dynamin, decreases Cu-induced endocytosis of CTR1, as does a dynamin inhibitor and clathrin knockdown using siRNA. Utilizing imaging, siRNA techniques and a new high-throughput assay for endocytosis employing CLIP-tag methodology, we show that internalized CTR1 accumulates in early sorting endosomes and recycling compartments (containing Rab5 and EEA1), but not in late endosomes or lysosomal pathways. Using live cell fluorescence, we find that upon extracellular Cu removal CTR1 recycles to the cell surface through the slower-recycling Rab11-mediated pathway. These processes enable cells to dynamically alter transporter levels at the plasma membrane and acutely modulate entry as a safeguard against excess cellular Cu.
Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy
Authors: Scotton Chiara , Bovolenta Matteo , Schwartz Elena , Falzarano Maria Sofia , Martoni Elena , Passarelli Chiara , Armaroli Annarita , Osman Hana , Rodolico Carmelo , Messina Sonia , Pegoraro Elena , D'Amico Adele , Bertini Enrico , Gualandi Francesca , Neri Marcella , Selvatici Rita , Boffi Patrizia , Maioli Maria Antonietta , Lochmüller Hanns , Straub Volker , Bushby Katherine , Castrignanò Tiziana , Pesole Graziano , Sabatelli Patrizia , Merlini Luciano , Braghetta Paola , Bonaldo Paolo , Bernardi Paolo , Foley Reghan , Cirak Sebahattin , Zaharieva Irina , Muntoni Francesco , Capitanio Daniele , Gelfi Cecilia , Kotelnikova Ekaterina , Yuryev Anton , Lebowitz Michael , Zhang Xiping , Hodge Brian A. , Esser Karyn A. , Ferlini Alessandra 
Published: March 2016

ABSTRACT
Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1−/−) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1−/− mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1−/− (also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene–environment interactions that might modify muscle damage pathogenesis.
Use of Low Level of Continuous Heat as an Adjunct to Physical Therapy Improves Knee Pain Recovery and the Compliance for Home Exercise in Patients With Chronic Knee Pain: A Randomized Controlled Trial
Authors: Petrofsky Jerrold S. , Laymon Michael S. , Alshammari Faris S. , Lee Haneul 
Published: March 2016

Abstract
Petrofsky, JS, Laymon, MS, Alshammari, FS, and Lee, H. Use of low level of continuous heat as an adjunct to physical therapy improves knee pain recovery and the compliance for home exercise in patients with chronic knee pain: a randomized controlled trial. J Strength Cond Res 30(11): 3107–3115, 2016—This study examined if the use of low level continuous heat (LLCH) wraps at home between physical therapy sessions at a clinic resulted in better therapy outcomes in patients with chronic knee pain. Fifty individuals with chronic nonspecific knee pain was randomly allocated to 2 groups: the LLCH group and the placebo group. All subjects underwent 1 hour of conventional physical therapy twice per week for 2 weeks at the outpatient clinic and they were asked to accomplish 1 hour of therapeutic exercise at home each day between sessions. The LLCH group applied LLCH knee wraps for 6 hours at home before home exercise while placebo group took a placebo ibuprofen. (This was done since placebo heat is impossible to use since subjects would notice that the wraps were cold) Before, during, and after intervention, pain intensity, active range of motion of the knee (AROM), knee strength, and home exercise compliance were measured. The LLCH group showed pain attenuation after 2 weeks of therapy sessions (p ≤ 0.05). AROM and strength of the knee significantly improved over time compared to the placebo group. Home exercise compliance was significantly higher in the LLCH group than placebo group (p ≤ 0.05). These results indicated that the use of LLCH as an adjunct to conventional physical therapy for chronic knee pain significantly improved pain attenuation and recovery of strength and movement in patients with chronic knee pain.
Test-Retest Reliability of a Novel Isokinetic Squat Device With Strength-Trained Athletes
Authors: Bridgeman Lee A. , McGuigan Michael R. , Gill Nicholas D. , Dulson Deborah K. 
Published: March 2016

Abstract
Bridgeman, LA, McGuigan, MR, Gill, ND, and Dulson, DK. Test-retest reliability of a novel isokinetic squat device with strength-trained athletes. J Strength Cond Res 30(11): 3261–3265, 2016—The aim of this study was to investigate the test-retest reliability of a novel multijoint isokinetic squat device. The subjects in this study were 10 strength-trained athletes. Each subject completed 3 maximal testing sessions to assess peak concentric and eccentric force (N) over a 3-week period using the Exerbotics squat device. Mean differences between eccentric and concentric force across the trials were calculated. Intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) for the variables of interest were calculated using an excel reliability spreadsheet. Between trials 1 and 2 an 11.0 and 2.3% increase in mean concentric and eccentric forces, respectively, was reported. Between trials 2 and 3 a 1.35% increase in the mean concentric force production and a 1.4% increase in eccentric force production was reported. The mean concentric peak force CV and ICC across the 3 trials was 10% (7.6–15.4) and 0.95 (0.87–0.98) respectively. However, the mean eccentric peak force CV and ICC across the trials was 7.2% (5.5–11.1) and 0.90 (0.76–0.97), respectively. Based on these findings it is suggested that the Exerbotics squat device shows good test-retest reliability. Therefore practitioners and investigators may consider its use to monitor changes in concentric and eccentric peak force.
Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature
Authors: Appelman-Dijkstra Natasha M , Rijndorp Marnick , Biermasz Nienke R , Dekkers Olaf M , Pereira Alberto M 
Published: March 2016

Background
Recombinant human growth hormone (rhGH) replacement is advocated in adult growth hormone-deficient (GHD) patients to increase bone mass and improve lipid profile, body composition, and quality of life. The long-term effects of discontinuation of rhGh replacement are unknown.

Methods
This cohort study and systematic review aim to evaluate the long-term metabolic effects of discontinuation of rhGh replacement in adult GHD patients, with a subgroup analyses according to age (< or > 60 years). Data on anthropometry, lipids, glucose, and bone mass density (BMD) were assessed for 3 years after discontinuation.

Results
Cohort study included 64 patients who had discontinued rhGh replacement for >12 months. Fat percentage increased from 31.5±9.5% to 33.8±9.0% (mean difference 2.3, P=0.003). BMI decreased only in subjects <60 years (P=0.014). Glucose, total cholesterol, and LDL-cholesterol levels did not change; however, the percentage of patients on statins increased slightly from 39% to 44%. HDL-C concentration increased only in patients <60 years (mean difference 0.2, P=0.043). Lumbar spine BMD did not change; however, femoral neck BMD and bone turnover markers decreased in subjects <60 years (P=0.001). Systematic review included eight studies (n=166 patients) with a follow-up duration of 6–18 months. Of the eight studies, three qualified as low risk of bias and five as having an intermediate risk of bias. None of the studies reported handling of statins, bisphosphonates, and glucose-lowering medication or excluded patients using these medications.

Conclusions
In this study, discontinuation of rhGh replacement resulted in metabolic changes only in patients <60 years after 3 years. Further research warrants to determine the optimal strategies for (dis)continuation of rhGh replacement in adult patients with GHD.
Whole-Genome Analysis of Individual Meiotic Events in Drosophila melanogaster Reveals That Noncrossover Gene Conversions Are Insensitive to Interference and the Centromere Effect
Authors: Miller Danny E , Smith Clarissa B , Kazemi Nazanin Yeganeh , Cockrell Alexandria J , Arvanitakis Alexandra V , Blumenstiel Justin P , Jaspersen Sue L , Hawley R Scott 
Published: March 2016

Abstract
A century of genetic analysis has revealed that multiple mechanisms control the distribution of meiotic crossover events. In Drosophila melanogaster, two significant positional controls are interference and the strongly polar centromere effect. Here, we assess the factors controlling the distribution of crossovers (COs) and noncrossover gene conversions (NCOs) along all five major chromosome arms in 196 single meiotic divisions to generate a more detailed understanding of these controls on a genome-wide scale. Analyzing the outcomes of single meiotic events allows us to distinguish among different classes of meiotic recombination. In so doing, we identified 291 NCOs spread uniformly among the five major chromosome arms and 541 COs (including 52 double crossovers and one triple crossover). We find that unlike COs, NCOs are insensitive to the centromere effect and do not demonstrate interference. Although the positions of COs appear to be determined predominately by the long-range influences of interference and the centromere effect, each chromosome may display a different pattern of sensitivity to interference, suggesting that interference may not be a uniform global property. In addition, unbiased sequencing of a large number of individuals allows us to describe the formation of de novo copy number variants, the majority of which appear to be mediated by unequal crossing over between transposable elements. This work has multiple implications for our understanding of how meiotic recombination is regulated to ensure proper chromosome segregation and maintain genome stability.
The Dimensionality of Genomic Information and Its Effect on Genomic Prediction
Authors: Pocrnic Ivan , Lourenco Daniela A L , Masuda Yutaka , Legarra Andres , Misztal Ignacy 
Published: March 2016

Abstract
The genomic relationship matrix (GRM) can be inverted by the algorithm for proven and young (APY) based on recursion on a random subset of animals. While a regular inverse has a cubic cost, the cost of the APY inverse can be close to linear. Theory for the APY assumes that the optimal size of the subset (maximizing accuracy of genomic predictions) is due to a limited dimensionality of the GRM, which is a function of the effective population size (Ne). The objective of this study was to evaluate these assumptions by simulation. Six populations were simulated with approximate effective population size (Ne) from 20 to 200. Each population consisted of 10 nonoverlapping generations, with 25,000 animals per generation and phenotypes available for generations 1–9. The last 3 generations were fully genotyped assuming genome length L = 30. The GRM was constructed for each population and analyzed for distribution of eigenvalues. Genomic estimated breeding values (GEBV) were computed by single-step GBLUP, using either a direct or an APY inverse of GRM. The sizes of the subset in APY were set to the number of the largest eigenvalues explaining x% of variation (EIGx, x = 90, 95, 98, 99) in GRM. Accuracies of GEBV for the last generation with the APY inverse peaked at EIG98 and were slightly lower with EIG95, EIG99, or the direct inverse. Most information in the GRM is contained in ∼NeL largest eigenvalues, with no information beyond 4NeL. Genomic predictions with the APY inverse of the GRM are more accurate than by the regular inverse.
El litio en la historia de la psicofarmacología.
Authors: Castillo Aitor 
Published: March 2016

El primer estudio para probar la eficacia deltratamiento de mantenimiento con litio fue abierto einvolucró a 88 pacientes maniaco-depresivos que fueronseguidos por 6 años. El tratamiento produjo marcadosy duraderos efectos sobre la enfermedad de estaspersonas, quienes habían presentado un promedio de5 episodios previos o depresión a lo largo de sus vidas.
Temperature and Probe‐to‐Probe Variability Effects on the Performance of Capacitance Soil Moisture Sensors in an Oxisol
Authors: Fares Ali , Safeeq Mohammad , Awal Ripendra , Fares Samira , Dogan Ahmet 
Published: March 2016

Core Ideas
Temperature variability and hysteresis and probe variability affect sensor measurements.
Probe‐to‐probe variability is significant but random.
Temperature variability is the major source of error in sensor performance.
Magnitude of temperature‐induced error is a function of water content and sensor type.
Dependent calibration functions could improve sensor measurement performance.
Reliable and accurate monitoring of soil water content (θ) across the landscape is indispensable for many water resources applications. Capacitance‐based in situ soil water content measuring devices are extensively used despite their sensitivity to soil properties besides water content, e.g., temperature and organic matter content. The main goals of this study were to: (i) examine the effects of temperature, hysteresis of the temperature response, and probe‐to‐probe variability on the performance of three (5TE, EC‐5, and EC‐TM) single capacitance sensors (SCS) in a Hawaiian Oxisol; and (ii) develop empirical calibration equations to correct for temperature and improve measurement accuracy. The SCS raw output and thermocouple temperature measurements were recorded at 1‐min intervals during heating and cooling cycles between 1 and 45°C. The three SCS and thermocouples were inserted in uniformly packed soils with θ varying from 0 to 0.55 m3 m−3. We used three probes for each SCS, and the entire experiment was replicated with two heating and cooling cycles. Temperature, hysteresis, and the probe‐to‐probe variability effects were highly significant (p < 0.05) for all three SCS. Estimated θ using soil‐specific calibrations at 25°C significantly increased with increasing temperature for all SCS. The 5TE sensor showed increasing temperature sensitivity with increasing water content. However, the EC‐5 and EC‐TM sensors exhibited a bidirectional response to temperature, with the highest sensitivity at ∼0.10 m3 m−3 water content. An empirically derived temperature‐dependent calibration equation substantially reduced the variability (>90% reduction in interquartile range) in measured water content due to changing soil temperature. Applying differing temperature corrections for heating and cooling did not improve the calibration any further.
Experimental Evaluation of Earthworm and Plant Root Soil Penetration–Cavity Expansion Models Using Cone Penetrometer Analogs
Authors: Ruiz Siul , Straub Isabelle , Schymanski Stanislaus J. , Or Dani 
Published: March 2016

Core Ideas
Analytic model for penetration–expansion forces closely agrees with measurements.
Measurements used cones with size geometry similar to earthworms and roots.
Soil parameters and constraints for root and earthworm bioturbation are estimated.
To form new burrows, earthworms need to consume 0.3 kg C m−2 yr−1.
Recent mechanical models of soil penetration by earthworms and plant roots based on penetration‐cavity expansion were tested using cone penetration measurements at scales compatible with the sizes of earthworms and plant roots. Measurements using different cone radii (1.0–2.5 mm) and cone semi‐apex angles (15–30°) were obtained for a range of soils and water contents at highly resolved penetration forces and constant insertion rates. The cone penetration measurements were interpreted using independently determined soil mechanical parameters and yielded good agreement with predictions from an analytical mechanical model. Experimental confirmation of penetration force predictions supports estimates of energy costs associated with soil bioturbation that vary with soil hydration status and mechanical characteristics. Effects of soil friction and axial compaction were assessed by comparing the results from conventional and recessed cones (to eliminate soil–shaft friction). The study provides new insights into quantitative soil bioturbation processes and expands predictive capabilities of the mechanics and energetics of earthworm activity and root zone dynamics related to soil structure development.