bluuebunny/crossref_metadata_2025 huggingface dataset:
Coarse‐Grained and Atomistic MD Simulations of RNA and DNA Folding
Authors: Leuchter Jessica D. , Green Adam T. , Gilyard Julian , Rambarat Cecilia G. , Cho Samuel S.
Published: May 2014

Although the main features of the protein folding problem are coming into clearer focus, the microscopic viewpoint of nucleic acid folding mechanisms is only just beginning to be addressed. Experiments, theory, and simulations are pointing to complex thermodynamic and kinetic mechanisms. As is the case for proteins, molecular dynamics (MD) simulations continue to be indispensable tools for providing a molecular basis for nucleic acid folding mechanisms. In this review, we provide an overview of biomolecular folding mechanisms focusing on nucleic acids. We outline the important interactions that are likely to be the main determinants of nucleic acid folding energy landscapes. We discuss recent MD simulation studies of empirical force field and Go‐type MD simulations of RNA and DNA folding mechanisms to outline recent successes and the theoretical and computational challenges that lie ahead.
Effective release of a broad spectrum antibiotic from elastin‐like polypeptide‐collagen composite
Authors: Anderson Tiffany R. , Marquart Mary E. , Janorkar Amol V.
Published: May 2014

Preparation of hydrogels that possess an effective antibiotic release profile and better mechanical properties compared to the traditionally used collagen hydrogels has the potential to minimize post‐surgical infections and support wound healing. Toward this goal, we prepared elastin‐like polypeptide (ELP)‐collagen composite hydrogels that displayed a significantly higher elastic modulus compared to the collagen hydrogels. We then characterized the release behavior of the collagen and ELP‐collagen hydrogels loaded with varying dosages (1–5% w/w) of a commonly used broad spectrum antibiotic, doxycycline hyclate. Both collagen and ELP‐collagen hydrogels showed a gradual time dependent doxycycline release over a period of 5 days. The ELP‐collagen hydrogels, in general, showed a slower release of the doxycycline compared to the collagen hydrogels. The released doxycycline was found to be effective against four bacterial strains (Escherichia coli,Pseudomonas aeruginosa,Streptococcus sanguinis, andmethicillin‐resistant Staphylococcus aureus) in a dose dependent manner. Combined with their improved mechanical properties, the gradual and effective drug release from the biocompatible ELP‐collagen hydrogels shown here may be beneficial for drug delivery and tissue engineering applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 782–790, 2015.
Investigating the solubility and cytocompatibility of CaO–Na2O–SiO2/TiO2 bioactive glasses
Authors: Wren Anthony W. , Coughlan Aisling , Smith Courtney M. , Hudson Sarah P. , Laffir Fathima R. , Towler Mark R.
Published: May 2014

This study aims to investigate the solubility of a series of titanium (TiO2)‐containing bioactive glasses and their subsequent effect on cell viability. Five glasses were synthesized in the composition range SiO2–Na2O–CaO with 5 mol % of increments TiO2 substituted for SiO2. Glass solubility was investigated with respect to (1) exposed surface area, (2) particle size, (3) incubation time, and (4) compositional effects. Ion release profiles showed that sodium (Na+) presented high release rates after 1 day and were unchanged between 7 and 14 days. Calcium (Ca2+) release presented a significant change at each time period and was also composition dependent, where a reduction in Ca2+ release is observed with an increase in TiO2 concentration. Silica (Si4+) release did not present any clear trends while no titanium (Ti4+) was released. Cell numbers were found to increase up to 44%, compared to the growing control population, with a reduction in particle size and with the inclusion of TiO2 in the glass composition. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 709–720, 2015.
Morphology effect of bioglass‐reinforced hydroxyapatite (Bonelike®) on osteoregeneration
Authors: Atayde L. M. , Cortez P. P. , Afonso A. , Santos M. , Maurício A. C. , Santos J. D.
Published: May 2014

In the last decades, the well‐known disadvantages of autografts and allografts have driven to the development of synthetic bone grafts for bone regeneration. Bonelike®, a glass‐reinforced hydroxyapatite (HA) composite was developed and registered for bone grafting. This biomaterial is composed by a modified HA matrix, with α‐ and β‐tricalcium phosphate secondary phases. Aiming to improve the biological characteristics of Bonelike®, new spherical pelleted granules, of different shape and size, were developed with controlled micro and macrostructure. In the present study, it was compared the physicochemical properties and in vivo performance of different Bonelike® granule presentations—Bonelike® polygonal (500–1000 µm size) and Bonelike spherical (250–500 µm; 500–1000 µm size). For the in vivo study, Bonelike® was implanted on sheep femurs, with various implantation times (30 days, 60 days, 120 days, and 180 days). X‐ray diffraction analysis revealed that the phase composition of different granules presentations was similar. Bonelike® spherical 500–1000 µm was the most porous material (global porosity and intraporosity) and Bonelike® polygonal 500–1000 µm the less porous. Considering the in vivo study, both polygonal and spherical granules presented osteoconductive proprieties. The spherical granules showed several advantages, including easier medical application through syringe and improved osteointegration, osteoconduction, and degradation, by the presence of larger pores, controlled micro‐ and macrosctructure and suitable particle format that adapts to bone growth. Bonelike® spherical 500–1000 µm showed improved new bone invasion throughout the material's structure and Bonelike® spherical 250–500 µm appeared to induce faster bone regeneration, presenting less unfilled areas and less lacunae in the histological analysis. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 292–304, 2015.
Bioactivity evolution of the surface functionalized bioactive glasses
Authors: Magyari Klára , Baia Lucian , Vulpoi Adriana , Simon Simion , Popescu Octavian , Simon Viorica
Published: May 2014

The formation of a calcium phosphate layer on the surface of the SiO2–CaO–P2O5 glasses after immersion in simulated body fluid (SBF) generally demonstrates the bioactivity of these materials. Grafting of the surface by chemical bonding can minimize the structural changes in protein adsorbed on the surface. Therefore, in this study our interest was to evaluate the bioactivity and blood biocompatibility of the SiO2–CaO–P2O5 glasses after their surface modification by functionalization with aminopropyl‐triethoxysilane and/or by fibrinogen. It is shown that the fibrinogen adsorbed on the glass surfaces induces a growing of the apatite‐like layer. It is also evidenced that the protein content from SBF influences the growth of the apatite‐like layer. Furthermore, the good blood compatibility of the materials after fibrinogen and bovine serum albumin adsorption is proved from the assessment of the β‐sheet–β‐turn ratio. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 261–272, 2015.
Long-Term Proton Pump Inhibitor Therapy and Falls and Fractures in Elderly Women: A Prospective Cohort Study
Authors: Lewis Joshua R , Barre Deka , Zhu Kun , Ivey Kerry L , Lim EE Mun , Hughes Jeff , Prince Richard L
Published: May 2014

Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance-related function in a post hoc analysis of a longitudinal population-based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25–3.77; p = 0.006 and 1.95; 95% CI, 1.20–3.16; p = 0.007, respectively. In the replication study, long-term PPI use was associated with an increased risk of self-reported falling; AOR, 1.51; 95% CI, 1.00–2.27; p = 0.049. No association of long-term PPI therapy with bone structure was observed; however, questionnaire-assessed falls-associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p < 0.001) and numbness of feet (p = 0.017) and objective clinical measurement such as Timed Up and Go (p = 0.002) and Romberg eyes closed (p = 0.025) tests were all significantly impaired in long-term PPI users. Long-term PPI users were also more likely to have low vitamin B12 levels than non-users (50% versus 21%, p = 0.003). In conclusion, similar to previous studies, we identified an increased fracture risk in subjects on long-term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy. © 2014 American Society for Bone and Mineral Research.
Estimated Lean Mass and Fat Mass Differentially Affect Femoral Bone Density and Strength Index but Are Not FRAX Independent Risk Factors for Fracture
Authors: Leslie William D , Orwoll Eric S , Nielson Carrie M , Morin Suzanne N , Majumdar Sumit R , Johansson Helena , Odén Anders , McCloskey Eugene V , Kanis John A
Published: May 2014

Although increasing body weight has been regarded as protective against osteoporosis and fractures, there is accumulating evidence that fat mass adversely affects skeletal health compared with lean mass. We examined skeletal health as a function of estimated total body lean and fat mass in 40,050 women and 3600 men age ≥50 years at the time of baseline dual-energy X-ray absorptiometry (DXA) testing from a clinical registry from Manitoba, Canada. Femoral neck bone mineral density (BMD), strength index (SI), cross-sectional area (CSA), and cross-sectional moment of inertia (CSMI) were derived from DXA. Multivariable models showed that increasing lean mass was associated with near-linear increases in femoral BMD, CSA, and CSMI in both women and men, whereas increasing fat mass showed a small initial increase in these measurements followed by a plateau. In contrast, femoral SI was relatively unaffected by increasing lean mass but was associated with a continuous linear decline with increasing fat mass, which should predict higher fracture risk. During mean 5-year follow-up, incident major osteoporosis fractures and hip fractures were observed in 2505 women and 180 men (626 and 45 hip fractures, respectively). After adjustment for fracture risk assessment tool (FRAX) scores (with or without BMD), we found no evidence that lean mass, fat mass, or femoral SI affected prediction of major osteoporosis fractures or hip fractures. Findings were similar in men and women, without significant interactions with sex or obesity. In conclusion, skeletal adaptation to increasing lean mass was positively associated with BMD but had no effect on femoral SI, whereas increasing fat mass had no effect on BMD but adversely affected femoral SI. Greater fat mass was not independently associated with a greater risk of fractures over 5-year follow-up. FRAX robustly predicts fractures and was not affected by variations in body composition. © 2014 American Society for Bone and Mineral Research.
Ablation of Osteopontin Improves the Skeletal Phenotype of Phospho1
−/− Mice
Authors: Yadav Manisha C , Huesa Carmen , Narisawa Sonoko , Hoylaerts Marc F , Moreau Alain , Farquharson Colin , Millán José Luis
Published: May 2014

PHOSPHO1 and tissue-nonspecific alkaline phosphatase (TNAP) have nonredundant functions during skeletal mineralization. Although TNAP deficiency (Alpl−/− mice) leads to hypophosphatasia, caused by accumulation of the mineralization inhibitor inorganic pyrophosphate (PPi), comparably elevated levels of PPi in Phospho1−/− mice do not explain their stunted growth, spontaneous fractures, bowed long bones, osteomalacia, and scoliosis. We have previously shown that elevated PPi in Alpl−/− mice is accompanied by elevated osteopontin (OPN), another potent mineralization inhibitor, and that the amount of OPN correlates with the severity of hypophosphatasia in mice. Here we demonstrate that plasma OPN is elevated and OPN expression is upregulated in the skeleton, particularly in the vertebrae, of Phospho1−/− mice. Liquid chromatography/tandem mass spectrometry showed an increased proportion of phosphorylated OPN (p-OPN) peptides in Phospho1−/− mice, suggesting that accumulation of p-OPN causes the skeletal abnormalities in Phospho1−/− mice. We also show that ablation of the OPN gene, Spp1, leads to improvements in the skeletal phenotype in Phospho1−/− as they age. In particular, their scoliosis is ameliorated at 1 month of age and is completely rescued at 3 months of age. There is also improvement in the long bone defects characteristic of Phospho1−/− mice at 3 months of age. Mineralization assays comparing [Phospho1−/−; Spp1−/−], Phospho1−/−, and Spp1−/− chondrocytes display corrected mineralization by the double knockout cells. Expression of chondrocyte differentiation markers was also normalized in the [Phospho1−/−; Spp1−/−] mice. Thus, although Alpl and Phospho1 deficiencies lead to similar skeletal phenotypes and comparable changes in the expression levels of PPi and OPN, there is a clear dissociation in the hierarchical roles of these potent inhibitors of mineralization, with elevated PPi and elevated p-OPN levels causing the respective skeletal phenotypes in Alpl−/− and Phospho1−/− mice. © 2014 American Society for Bone and Mineral Research.
Altered Signaling in the G1 Phase Deregulates Chondrocyte Growth in a Mouse Model With Proteoglycan Undersulfation
Authors: Leonardis Fabio De , Monti Luca , Gualeni Benedetta , Tenni Ruggero , Forlino Antonella , Rossi Antonio
Published: May 2014

In several skeletal dysplasias defects in extracellular matrix molecules affect not only the structural and mechanical properties of cartilage, but also the complex network of signaling pathways involved in cell proliferation and differentiation. Sulfated proteoglycans, besides playing an important structural role in cartilage, are crucial in modulating the transport, diffusion, and interactions of growth factors with their specific targets, taking part in the regulation of signaling pathways involved in skeletal development and growth. In this work, we investigated by real time PCR and Western blots of the microdissected growth plate and by immunohistochemistry the molecular basis of reduced chondrocyte proliferation in the growth plate of the dtd mouse, a chondrodysplastic model with defective chondroitin sulfate proteoglycan sulfation of articular and growth plate cartilage. We detected activation of the Wnt pathway, leading to an increase in the non‐phosphorylated form of nuclear β‐catenin and subsequent up‐regulation of cyclin D1 expression in the G1 phase of the cell cycle. β‐Catenin was further stabilized by up‐regulation of Smad3 expression through TGF‐β pathway synergistic activation. We demonstrate that notwithstanding cyclin D1 expression increase, cell cycle progression is compromised in the G1 phase due to reduced phosphorylation of the pocket protein p130 leading to inhibition of transcription factors of the E2F family which are crucial for cell cycle progression and DNA replication. These data, together with altered Indian hedgehox signaling detected previously, explain at the molecular level the reduced chondrocyte proliferation rate of the dtd growth plate leading to reduced skeletal growth. J. Cell. Biochem. 115: 1779–1786, 2014. © 2014 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.
A p53‐Dependent Tumor Suppressor Network Is Induced by Selective miR‐125a‐5p Inhibition in Multiple Myeloma Cells
Authors: Leotta Marzia , Biamonte Lavinia , Raimondi Lavinia , Ronchetti Domenica , Di Martino Maria Teresa , Botta Cirino , Leone Emanuela , Pitari Maria Rita , Neri Antonino , Giordano Antonio , Tagliaferri Pierosandro , Tassone Pierfrancesco , Amodio Nicola
Published: May 2014

The analysis of deregulated microRNAs (miRNAs) is emerging as a novel approach to disclose the regulation of tumor suppressor or tumor promoting pathways in tumor cells. Targeting aberrantly expressed miRNAs is therefore a promising strategy for cancer treatment. By miRNA profiling of primary plasma cells from multiple myeloma (MM) patients, we previously reported increased miR‐125a‐5p levels associated to specific molecular subgroups. On these premises, we aimed at investigating the biological effects triggered by miR‐125a‐5p modulation in MM cells. Expression of p53 pathway‐related genes was down‐regulated in MM cells transfected with miR‐125a‐5p mimics. Luciferase reporter assays confirmed specific p53 targeting at 3′UTR level by miR‐125a‐5p mimics. Interestingly, bone marrow stromal cells (BMSCs) affected the miR‐125a‐5p/p53 axis, since adhesion of MM cells to BMSCs strongly up‐regulated miR‐125a‐5p levels, while reduced p53 expression. Moreover, ectopic miR‐125a‐5p reduced, while miR‐125‐5p inhibitors promoted, the expression of tumor suppressor miR‐192 and miR‐194, transcriptionally regulated by p53. Lentiviral‐mediated stable inhibition of miR‐125a‐5p expression in wild‐type p53 MM cells dampened cell growth, increased apoptosis and reduced cell migration. Importantly, inhibition of in vitro MM cell proliferation and migration was also achieved by synthetic miR‐125a‐5p inhibitors and was potentiated by the co‐expression of miR‐192 or miR‐194. Taken together, our data indicate that miR‐125a‐5p antagonism results in the activation of p53 pathway in MM cells, underlying the crucial role of this miRNA in the biopathology of MM and providing the molecular rationale for the combinatory use of miR‐125a inhibitors and miR‐192 or miR‐194 mimics for MM treatment. J. Cell. Physiol. 229: 2106–2116, 2014. © 2014 Wiley Periodicals, Inc.
Comparison of hollow fiber membrane and solvent extraction techniques for extraction of cerium and preparation of ceria by stripping precipitation
Authors: Rout Pradeep C. , Sarangi Kadambini
Published: May 2014

BACKGROUND

The extraction of cerium by hollow fiber supported liquid membrane using tri‐octyl methyl ammonium chloride (TOMAC) as mobile carrier was studied and the result was compared with solvent extraction data. The effect of different parameters such as pH, flow rates, extractant concentration, metal ion concentration and strip solution concentration on cerium extraction was investigated.

RESULTS

These parameters were optimized for maximum cerium flux and were found to be: pH 1.0, 0.1 mol L−1 TOMAC, 290 mL min−1 feed solution flow rate, 150 mL min−1 strip solution flow rate and 0.9 mol L−1 H2SO4 as strip solution. The parameters were also optimized for solvent extraction study. The number of stages and Aqueous:Organic (A:O) ratio for extraction and stripping were determined from McCabe–Thiele diagrams. The extracted species was determined to be (R3NCH3)2Ce(SO4)3. The selective separation of cerium in presence of various other metal ions such as iron, copper, zinc, cobalt, nickel and manganese using a hollow fiber supported liquid membrane (HFSLM) was carried out and the separation factor values were found to be in the order α Ce/Fe <αCe/Cu < αCe/Mn < αCe/Zn < αCe/Co < αCe/Ni. Finally highly pure (99.99%) CeO2 was prepared by stripping precipitation with oxalic acid and thermal decomposition at 900°C for 1 h.

CONCLUSION

The efficiency of hollow fiber supported liquid membrane was greater than that of solvent extraction for the extraction of cerium for the present system. © 2014 Society of Chemical Industry
Fourier transformed near infrared (FT‐NIR) spectroscopy for the estimation of parameters in pretreated lignocellulosic materials for bioethanol production
Authors: Monrroy Mariel , Garcia José Renán , Troncoso Eduardo , Freer Juanita
Published: May 2014

BACKGROUND

In the bioethanol production process it is necessary to know the physical and chemical characteristics of pretreated material which may affect the enzymatic hydrolysis as well as the carbohydrates potential for fermentation. In the present study, prediction models were developed with Fourier transformed near infrared (FT‐NIR) spectroscopy and multivariate analysis for the cellulose crystallinity index (CrI), saccharification and ethanol yield, and glucan, hemicellulose and lignin content. Prediction models were generated using Eucalyptus globulus and Pinus radiata samples from different pretreatments such as bio pretreatment, kraft process, steam explosion, organosolv and biorganosolv process.

RESULTS

The calibration models obtained by partial least‐squares (PLS), presented high coefficients of calibration and validation determination. The predictive ability of the calibration models developed was evaluated in a set of external samples. The properties were predicted with a prediction error (RMSEP) of 0.02, 1.4 g L−1, 2.0%, 0.9%, 1.0% and 1.9% for CrI, ethanol yield, saccharification, lignin, hemicellulose and glucan content, respectively.

CONCLUSION

These results suggest that it is possible to construct models for these properties with a database involving pulps from different pretreatments. NIR spectroscopy predictions provide useful and economic tools for rapid analysis of the large number of samples required in the assessment of bioethanol production processes. © 2014 Society of Chemical Industry
Chemometrics application in biotech processes: assessing comparability across processes and scales
Authors: Rathore Anurag S. , Mittal Shachi , Pathak Mili , Mahalingam Velu
Published: May 2014

BACKGROUND

Assessment of process comparability is often required across different phases of manufacturing (Phase I vs Phase II vs Phase III vs Commercial) as well as other key activities during product commercialization (process scale‐up, technology transfer, process improvement). In this work, chemometrics was applied to compare two versions of a biotech process and identify process steps where significant differences exist as well as the parameters that cause these differences.

RESULTS

The dataset used in this analysis consists of data from 229 manufacturing batches. Partial least squares has been used for modeling the data. Scatter plots and variable importance plots have been used for evaluating comparability. Process parameters identified as significant by using chemometrics have been compared against those identified from process characterization using traditional lab scale experimental studies. The comparison has been followed by discussion on the pros and cons of the two approaches. To our knowledge this is the first time that such a comparison has been published for biotech processing.

CONCLUSIONS

The study further demonstrates the usefulness of chemometrics in defining process comparability and in gathering process understanding from analysis of manufacturing data to supplement traditional lab‐scale experimentation. © 2014 Society of Chemical Industry
Study of 1,3‐Dipolar Cycloaddition and Ring Contraction of New 1,4‐Phenylene‐bis[1,5]benzothiazepine Derivatives
Authors: Chen Fei , Liu Fang‐Ming , Dong Zhi‐Qiang
Published: May 2014

Some 1,4‐phenylene‐bis[1,2,4]oxadiazolo‐[5,4‐d][1,5]benzothiazepine derivatives (4a, 4b, 4c) were synthesized by 1,3‐dipolar cycloaddition reaction of benzohydroximinoyl chloride with 1,4‐phenylene‐bis(4‐aryl)‐2,3‐dihydro[1,5]benzothiazepine (2a, 2b, 2c); meanwhile, compounds 2a, 2b, 2c also occurred ring contraction under acylating condition to obtain bis[2‐aryl‐2′‐(β‐1,4‐phenylenevinyl)‐3‐acetyl]‐2,3‐dihydro[1,5]benzothiazoles (3a, 3b, 3c). The structures of some novel compounds were confirmed by IR, 1H‐NMR, elemental, and X‐ray crystallographic analysis.
How does sonication affect the mineral and organic constituents of soil aggregates?—A review
Authors: Kaiser Michael , Asefaw Berhe Asmeret
Published: May 2014

Application of ultrasound to disperse soil aggregates has been critical in enabling researchers to separate and analyze aggregate building blocks that include organic and mineral particles as well as mineral associated organic matter. But the forces generated in the process may also alter the dispersion products and, thus, potentially interfere with the interpretation of experimental results. This review summarizes present knowledge on experimental conditions that may lead to physical damage and chemical modifications of aggregate building blocks. The energy level at which physical disintegration of organic particles could be detected was as low as 60 J mL–1. Physical damage of sand‐ and silt‐sized mineral particles was observed to commence at energy levels exceeding 700 J cm–3. No evidence was found for the disintegration of particles within the clay‐size fraction of soils even though studies analyzing pure minerals such as kaolinite revealed particle breakage after application of energy amounts > 12,000 J cm–3. Here we outline a strategy to minimize artifacts such as physical damage of mineral or organic particles resulting from ultrasonication by adopting a stepwise dispersion protocol involving successively higher energy levels, accompanied by a sequential separation of organic and mineral compounds.
Predictors of donor follow-up after living donor liver transplantation
Authors: Brown Robert S. , Smith Abigail R. , Dew Mary Amanda , Gillespie Brenda W. , Hill-Callahan Peg , Ladner Daniela P.
Published: May 2014

Donor safety in living liver donation is of paramount importance; however, information on long-term outcomes is limited by incomplete follow-up. We sought to ascertain factors that predicted postdonation follow-up in 456 living liver donors in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study. Completed donor follow-up was defined as physical, phone, or laboratory contact at a given time point. Univariate and multivariate mixed effects logistic regression models, using donor and recipient demographic and clinical data and donor quality-of-life data, were developed to predict completed follow-up. Ninety percent of the donors completed their follow-up in the first 3 months, and 83% completed their follow-up at year 1; rates of completed follow-up ranged from 57% to 72% in years 2 to 7 and from 41% to 56% in years 8 to 10. The probability of completed follow-up in the first year was higher for white donors [odds ratio (OR) = 3.27, 95% confidence interval (CI) = 1.25–8.58] but lower for donors whose recipients had hepatitis C virus or hepatocellular carcinoma (OR = 0.34, 95% CI = 0.17–0.69). After the first year, an older age at donation predicted more complete follow-up. There were significant center differences at all time points (OR range = 0.29–10.11), with center variability in both returns for in-center visits and the use of phone/long-distance visits. Donor follow-up in the first year after donation was excellent but decreased with time. Predictors of follow-up varied with the time since donation. In conclusion, adapting best center practices (enhanced through the use of telephones and social media) to maintain contact with donors represents a significant opportunity to gain valuable information about long-term donor outcomes. Liver Transpl 20:967–976, 2014. © 2014 AASLD.
Extending the Methylene Spacer Length of ADMET Hydroxy‐Functionalized Polymers
Authors: Thompson Donovan , Yamakado Ryohei , Wagener Kenneth B.
Published: May 2014

Solution acyclic diene metathesis (ADMET) polymerization using Grubbs' first‐generation catalyst leads to the direct synthesis of polymers containing hydroxyl groups. Secondary alcohols are placed precisely at specific intervals on an unsaturated hydrocarbon backbone. Increasing the number of methylene spacers decreases the frequency of the pendant groups from every 15th carbon to every 21st carbon. The complete hydrogenation of the unsaturated polymers yields model representatives of well‐defined ethylene–vinyl alcohol copolymers. Despite the decrease in branch frequency in both the homopolymers and randomized versions of such polymers, surprisingly, the precision does not have an influence on the thermal properties, and they are all similar in nature. It is concluded that hydrogen bonding dominates the polymer behavior, rather than the precision in hydroxyl‐group placement along the polyethylene chain.

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Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress
Authors: Yaffe Paul B. , Power Coombs Melanie R. , Doucette Carolyn D. , Walsh Mark , Hoskin David W.
Published: May 2014

Piperine, a piperidine alkaloid present in black pepper, inhibits the growth of cancer cells, although the mechanism of action is not well understood. In this study, we show that piperine (75–150 µM) inhibited the growth of several colon cancer cell lines but had little effect on the growth of normal fibroblasts and epithelial cells. Piperine inhibited HT‐29 colon carcinoma cell proliferation by causing G1 phase cell cycle arrest that was associated with decreased expression of cyclins D1 and D3 and their activating partner cyclin‐dependent kinases 4 and 6, as well as reduced phosphorylation of the retinoblastoma protein and up‐regulation of p21/WAF1 and p27/KIP1 expression. In addition, piperine caused hydroxyl radical production and apoptosis that was partially dependent on the production of reactive oxygen species. Piperine‐treated HT‐29 cells showed loss of mitochondrial membrane integrity and cleavage of poly (ADP‐ribose) polymerase‐1, as well as caspase activation and reduced apoptosis in the presence of the pan‐caspase inhibitor zVAD‐FMK. Increased expression of the endoplasmic reticulum stress‐associated proteins inositol‐requiring 1α protein, C/EBP homologous protein, and binding immunoglobulin protein, and activation of c‐Jun N‐terminal kinase and p38 mitogen‐activated protein kinase, as well as decreased phosphorylation of Akt and reduced survivin expression were also observed in piperine‐treated HT‐29 cells. Furthermore, piperine inhibited colony formation by HT‐29 cells, as well as the growth of HT‐29 spheroids. Cell cycle arrest and endoplasmic reticulum stress‐associated apoptosis following piperine treatment of HT‐29 cells provides the first evidence that piperine may be useful in the treatment of colon cancer. © 2014 Wiley Periodicals, Inc.
Mesenchymal stem cells inhibit breast cancer cell migration and invasion through secretion of tissue inhibitor of metalloproteinase‐1 and ‐2
Authors: Clarke Mitchell R. , Imhoff Floriane M. , Baird Sarah K.
Published: May 2014

Mesenchymal stem cells (MSCs) form part of tumor stroma, and are typically considered to be pro‐tumorigenic, promoting continuing tumor growth and metastasis. Here, we describe a mechanism by which MSCs may be anti‐tumorigenic, through inhibition of breast cancer cell migration and invasion, an important part of metastasis. MDA‐MB‐231 and T47D cells were co‐cultured in a Transwell insert above MSCs or MSC conditioned media and their migration or invasion through Matrigel measured. The conditioned media was found to inhibit breast cancer cell movement. TIMP‐1 and TIMP‐2, inhibitors of matrix metalloproteinases (MMPs), were identified as candidates for this inhibition and enhanced secretion of MMPs was not sufficient to counter the anti‐migratory effects of TIMP expression. Inhibition of TIMP activity showed that TIMP‐1 and TIMP‐2 together were largely responsible for the reduction of migration and invasion by MSCs. Therefore, MSCs may play anti‐tumorigenic, anti‐metastatic roles in tumor development, with the overall outcome dependent upon the balance of pro‐and anti‐tumorigenic molecules secreted. © 2014 Wiley Periodicals, Inc.
Mortality in Parkinson's disease: A systematic review and meta‐analysis
Authors: Macleod Angus D. , Taylor Kate S.M. , Counsell Carl E.
Published: May 2014

This study was undertaken to perform a systematic review and meta‐analysis of studies of mortality in Parkinson's disease (PD) and to investigate which factors were associated with mortality. We conducted comprehensive searches of studies reporting a ratio of mortality in PD versus controls, descriptive survival measures, or factors predicting survival; assessed study quality; and extracted relevant data. Descriptive analysis, meta‐analysis, and meta‐regression were performed as appropriate. Eighty‐eight studies were included in the review with variable study methods and quality. Almost all studies reported increased mortality in PD (vs. controls), with mortality ratios ranging from 0.9 to 3.8, with major between‐study heterogeneity. Inception cohorts were more consistent with a pooled mortality ratio of approximately 1.5. Inception cohorts, measurements at longer follow‐up duration, and older study recruitment year were associated with lower mortality ratios, but these findings were not robust in sensitivity analyses. Within studies, mortality ratios increased over time. No robust evidence was found that mortality has decreased after the introduction of levodopa (L‐dopa). On average, PD survival reduced by approximately 5% every year of follow‐up, although there was significant heterogeneity. In post‐mortem studies, mean duration until death ranged from 6.9 to 14.3 years. Increasing age and presence of dementia were most commonly associated with increased mortality. Parkinson's disease is associated with increased mortality, but major heterogeneity is seen in estimates of mortality, which is probably explained by variable methodology and patient selection. Individual‐patient‐data meta‐analysis of high‐quality inception studies with long‐term follow‐up would be the optimal way to investigate the factors influencing mortality. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Involvement of dynamin 2 in actin‐based polar‐body extrusion during porcine oocyte maturation
Authors: Zhang Yu , Wang Qiao‐Chu , Han Jun , Cao Rui , Cui Xiang‐Shun , Kim Nam‐Hyung , Rui Rong , Sun Shao‐Chen
Published: May 2014

Mammalian oocyte meiotic maturation involves a unique asymmetric division, but the regulatory mechanisms and signaling pathways involved are poorly understood. Dynamins are ubiquitous eukaryotic GTPases involved in membrane trafficking and actin dynamics, whose roles in mammalian oocyte maturation have not been determined. In this study, we used porcine oocytes to show that Dynamin 2 accumulated at the meiotic spindle and in the cortex of oocytes, with a distribution similar to that of actin. Inhibiting Dynamin 2 activity in porcine oocytes with the specific inhibitor dynasore resulted in failed polar‐body extrusion. This phenotype may have been due to aberrant actin distribution and/or spindle positioning as inhibitor treatment disrupted the formation of the actin cap and cortical granule‐free domain, which negatively impacted spindle positioning. Moreover, the distribution of ARP2, a key actin‐nucleation factor, was severely reduced in the cortex after dynasore treatment. Thus, our results suggest that Dynamin 2 possibly regulates porcine oocyte maturation through its effects on actin‐mediated spindle positioning and cytokinesis, and that this may depend on regulating ARP2 localization. Mol. Reprod. Dev. 81: 725–734, 2014. © 2014 Wiley Periodicals, Inc.
Progressive obesity alters the steroidogenic response to ovulatory stimulation and increases the abundance of mRNAs stored in the ovulated oocyte
Authors: Pohlmeier William E. , Xie Fang , Kurz Scott G. , Lu Ningxia , Wood Jennifer R.
Published: May 2014

Obese women who are able to attain pregnancy are at increased risk for early‐pregnancy loss due, in part, to reduced oocyte quality. We and others have demonstrated that female Lethal Yellow (LY) mice and female C57BL/6 mice fed a high fat diet (B6‐HFD) exhibit phenotypes consistent with human obesity. These studies also showed that zygotes collected from LY and B6‐HFD females have reduced developmental competence. The current hypothesis is that LY and B6‐HFD females exhibit an abnormal response to gonadotropin stimulation compared to C57BL/6 controls fed normal rodent chow (B6‐ND), resulting in the ovulation of oocytes with an altered molecular phenotype which may contribute to its reduced developmental competence. To test this hypothesis, age‐matched B6‐ND, B6‐HFD, and LY females were stimulated with exogenous gonadotropins, then circulating hormone levels and the phenotypes of ovulated oocytes were analyzed. There was no difference in ovulation rate or in the percentage of morphologically abnormal oocytes collected from the oviduct of any females. Progesterone and progesterone/estradiol ratios, however, were increased in B6‐HFD and LY compared to B6‐ND females 16 hr post‐human chorionic gonadotropin treatment. The transcript abundance of several candidate oocyte genes was also increased in B6‐HFD‐ and LY‐derived oocytes compared to B6‐ND‐derived oocytes. These data suggest that increased insulin and leptin levels of obese females elevated circulating progesterone concentrations, altered transcriptional activity during oocyte growth, and/or impaired mechanisms of RNA translation and degradation during oocyte maturation. These changes in mRNA abundance likely contribute to reduced oocyte quality and the subsequent poor embryogenesis associated with obesity. Mol. Reprod. Dev. 81: 735–747, 2014. © 2014 Wiley Periodicals, Inc.
Complementary radial tagging for improved myocardial tagging contrast
Authors: Wang Zhe , Nasiraei‐Moghaddam Abbas , Reyhan Meral L. , Srinivasan Subashini , Finn J. Paul , Ennis Daniel B.
Published: May 2014

Purpose

To develop and evaluate complementary radial tagging (CRT) for improved myocardial tagging contrast.

Methods

We sought to develop and evaluate CRT, which aims to preserve the radial tag contrast throughout the cardiac cycle. Similar to complementary spatial modulation of magnetization, CRT acquires two sets of images with a phase shift in the tag pattern. The combination of a ramped imaging flip angle and image subtraction enhances tag contrast throughout the cardiac cycle. The proposed CRT technique uses a small table shift away from the isocenter to improve the uniformity of the radial tag pattern. We provide a mathematical solution for the optimal table shift and validate the solution in using a retrospective analysis of images from 500 patients in the Cardiac Atlas Project database.

Results

CRT simulations, phantom experiments, and in vivo images all demonstrate the improved tag contrast of CRT compared to RT. The retrospective evaluation demonstrated that acceptable CRT images could be acquired in over 98% of the clinical exams.

Conclusion

The CRT technique improves radial tag contrast throughout the cardiac cycle and should produce high quality tag patterns in nearly all patients. Magn Reson Med 73:1432–1440, 2015. © 2014 Wiley Periodicals, Inc.
Muscle activation varies with contraction mode in human spinal cord injury
Authors: Kim Hyosub E. , Thompson Christopher K. , Hornby T. George
Published: May 2014

Introduction: To better understand volitional force generation after chronic incomplete spinal cord injury (SCI), we examined muscle activation during single and repeated isometric, concentric, and eccentric knee extensor (KE) maximal voluntary contractions (MVCs). Methods: Torque and electromyographic (EMG) activity were recorded during single and repeated isometric and dynamic KE MVCs in 11 SCI subjects. Central activation ratios (CARs) were calculated for all contraction modes in SCI subjects and 11 healthy controls. Results: SCI subjects generated greater torque, KE EMG, and CARs during single eccentric vs. isometric and concentric MVCs (all P < 0.05). Torque and EMG remained similar during repeated eccentric MVCs; however, both increased during repeated isometric (>25%) and concentric (>30%) MVCs. Conclusions: SCI subjects demonstrated greater muscle activation during eccentric MVCs vs. isometric and concentric MVCs. This pattern of activation contrasts with the decreased eccentric activation demonstrated by healthy controls. Such information may aid development of novel rehabilitation interventions. Muscle Nerve 51: 235–245, 2015
LMO7‐null mice exhibit phenotypes consistent with emery‐dreifuss muscular dystrophy
Authors: Mull Aaron , Kim Gene , Holaska James M.
Published: May 2014

Introduction: Mutations in the inner nuclear envelope protein emerin cause Emery‐Dreifuss muscular dystrophy (EDMD), which is characterized by progressive skeletal muscle wasting, cardiac conduction defects, and tendon contractures. We previously showed that emerin binds directly to the transcription regulator Lmo7 and attenuates its activity to regulate the proper temporal expression of important myogenic differentiation genes. Methods: The skeletal muscle and cardiac phenotypes were analyzed in a newly generated Lmo7‐null mouse using histological analysis, echocardiography, and various neuromuscular tests to determine if Lmo7 was important for skeletal muscle and cardiac function. Results: Lmo7‐null mice had growth retardation, decreased fiber size, and impaired skeletal muscle and cardiac function. Lmo7‐null mice also had lower levels of phosphorylated retinoblastoma (Rb), extracellular signal‐regulated kinase, and c‐Jun N‐terminal kinase, which is consistent with altered Rb and mitogen‐activated protein kinase signaling. Conclusions: These findings demonstrate that loss of Lmo7 in mice causes myopathic phenotypes similar to those seen in other EDMD mouse models. Muscle Nerve 51: 222–228, 2015
SElf‐gated Non‐Contrast‐Enhanced FUnctional Lung imaging (SENCEFUL) using a quasi‐random fast low‐angle shot (FLASH) sequence and proton MRI
Authors: Fischer André , Weick Stefan , Ritter Christian O. , Beer Meinrad , Wirth Clemens , Hebestreit Helge , Jakob Peter M. , Hahn Dietbert , Bley Thorsten , Köstler Herbert
Published: May 2014

Obtaining functional information on the human lung is of tremendous interest in the characterization of lung defects and pathologies. However, pulmonary ventilation and perfusion maps usually require contrast agents and the application of electrocardiogram (ECG) triggering and breath holds to generate datasets free of motion artifacts. This work demonstrates the possibility of obtaining highly resolved perfusion‐weighted and ventilation‐weighted images of the human lung using proton MRI and the SElf‐gated Non‐Contrast‐Enhanced FUnctional Lung imaging (SENCEFUL) technique. The SENCEFUL technique utilizes a two‐dimensional fast low‐angle shot (FLASH) sequence with quasi‐random sampling of phase‐encoding (PE) steps for data acquisition. After every readout, a short additional acquisition of the non‐phase‐encoded direct current (DC) signal necessary for self‐gating was added. By sorting the quasi‐randomly acquired data according to respiratory and cardiac phase derived from the DC signal, datasets of representative respiratory and cardiac cycles could be accurately reconstructed. By application of the Fourier transform along the temporal dimension, functional maps (perfusion and ventilation) were obtained. These maps were compared with dynamic contrast‐enhanced (DCE, perfusion) as well as standard Fourier decomposition (FD, ventilation) reference datasets. All datasets were additionally scored by two experienced radiologists to quantify image quality. In addition, one initial patient examination using SENCEFUL was performed. Functional images of healthy volunteers and a patient diagnosed with hypoplasia of the left pulmonary artery and left‐sided pulmonary fibrosis were successfully obtained. Perfusion‐weighted images corresponded well to DCE‐MRI data; ventilation‐weighted images offered a significantly better depiction of the lung periphery compared with standard FD. Furthermore, the SENCEFUL technique hints at a potential clinical relevance by successfully detecting a perfusion defect in the patient scan. It can be concluded that SENCEFUL enables highly resolved ventilation‐ and perfusion‐weighted maps of the human lung to be obtained using proton MRI, and might be interesting for further clinical evaluation. Copyright © 2014 John Wiley & Sons, Ltd.
Classical and all‐floating FETI methods for the simulation of arterial tissues
Authors: Augustin Christoph M. , Holzapfel Gerhard A. , Steinbach Olaf
Published: May 2014

High‐resolution and anatomically realistic computer models of biological soft tissues play a significant role in the understanding of the function of cardiovascular components in health and disease. However, the computational effort to handle fine grids to resolve the geometries as well as sophisticated tissue models is very challenging. One possibility to derive a strongly scalable parallel solution algorithm is to consider finite element tearing and interconnecting (FETI) methods. In this study, we propose and investigate the application of FETI methods to simulate the elastic behavior of biological soft tissues. As one particular example, we choose the artery which is—as most other biological tissues—characterized by anisotropic and nonlinear material properties. We compare two specific approaches of FETI methods, classical and all‐floating, and investigate the numerical behavior of different preconditioning techniques. In comparison with classical FETI, the all‐floating approach not only has advantages concerning the implementation but also has advantages concerning the convergence of the global iterative solution method. This behavior is illustrated with numerical examples. We present results of linear elastic simulations to show convergence rates, as expected from the theory, and results from the more sophisticated nonlinear case where we apply a well‐known anisotropic model to the realistic geometry of an artery. Although the FETI methods have a great applicability on artery simulations, we will also discuss some limitations concerning the dependence on material parameters. Copyright © 2014 John Wiley & Sons, Ltd.
Equivalent polynomials for quadrature in Heaviside function enriched elements
Authors: Ventura G. , Benvenuti E.
Published: May 2014

One of the advantages of partition‐of‐unity FEMs, like the extended FEM, is the ability of modeling discontinuities independent of the mesh structure. The enrichment of the element functional space with discontinuous or non‐differentiable functions requires, when the element stiffness is computed, partitioning into subdomains for quadrature. However, the arbitrary intersection between the base mesh and the discontinuity plane generates quadrature subdomains of complex shape. This is particularly true in three‐dimensional problems, where quite sophisticate methodologies have been presented in the literature for the element stiffness evaluation.

The present work addresses the problem of Heaviside function enrichments and is based on the replacement of the discontinuous enrichment function with the limit of an equivalent polynomial defined on the entire element domain. This allows for the use of standard Gaussian quadrature in the elements crossed by the discontinuity. The work redefines conceptually the first version of the equivalent polynomial methodology introduced in 2006, allowing a much broader applicability. As a consequence, equivalent polynomials can be computed for all continuum element families in one, two, and three dimensions. Copyright © 2014 John Wiley & Sons, Ltd.