bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of molecular weight on the intrinsic immunogenic activity of poly(beta amino esters)
Authors: Andorko James I. , Pineault Kevin G. , Jewell Christopher M. 
Published: December 2016

AbstractPolymeric carriers are ubiquitously studied in vaccine and drug delivery to control the encapsulation, kinetics, and targeting of cargo. Recent research reveals many polymers can cause immunostimulatory and inflammatory responses, even in the absence of other immune signals. However, the extent to which this intrinsic immunogenicity evolves during degradation is understudied. Here we synthesized a small library of poly(beta amino esters) (PBAEs) that exhibit different starting molecular weights (MWs), but with similar and rapid degradation rates. Primary dendritic cells (DCs) treated with free PBAEs, either intact or degraded to form low MW fragments, were not activated. In contrast particles formed from PBAEs at different extents of degradation caused differential expression of classical DC activation markers (for example, CD40, CD80, CD86, MHCII), as well as antigen presentation. During degradation, activation levels changed with changing physicochemical properties (for example, MW, concentration, size, charge). Of note, irrespective of starting MW, immunogenicity peaked when the MW of degrading PBAEs decreased to a range of ∼1500–3000 Da. These findings could help inform design of future carriers that exploit the dynamic interactions with the immune system as materials degrade, leading to carriers that deliver cargo but also help direct the immune responses to vaccine or immunotherapy cargo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1219–1229, 2017.
Individual evaluation of cardiac marker expression and self‐beating during cardiac differentiation of P19CL6 cells on different culture substrates
Authors: Yamaoka Tetsuji , Hirata Mitsuhi , Dan Takaaki , Yamashita Atsushi , Otaka Akihisa , Nakaoki Takahiko , Miskon Azizi , Kakinoki Sachiro , Mahara Atsushi 
Published: December 2016

AbstractCell‐based therapies using self‐beating cardiomyocytes have been attracting great attention for use in cardiac regeneration, although an effective procedure to improve cardiac differentiation and self‐beating induction is required. The purpose of this study is to clarify the effect of the culture substrate on cardiac maturation by separately evaluating the cardiac differentiation step and the beating induction step in vitro. To this end, the well‐studied cardiomyocyte‐like progenitor cell line P19CL6 and neonatal cardiomyocytes (NCMs) were selected and cultured on substrates coated with collagen type I (Col‐I), gelatin (Gel), fibronectin (FN), or poly‐l‐lysine (PLL). It was found that the cardiac differentiation step, which was assessed using cardiac marker gene expression (GATA‐binding protein 4 (GATA4), myocyte‐specific enhancer factor 2D (MEF2D), and hyperpolarization‐activated cyclic nucleotide‐gated potassium channel 4 (HCN4)) in the P19CL6 embryonal carcinoma cells, was greatly enhanced on Col‐I, Gel, and PLL. In contrast, the spontaneous beating step, which was directly assessed by counting the beating colonies and measuring contractile protein gene expression (α‐myosin heavy chain (α‐MHC), troponin C type 1 (TnC1), and troponin T type 2 (TnT2)) in the rat NCMs, was enhanced on the FN and PLL surfaces. In the present study, for the first time, it was found that PLL enhances both the cardiac differentiation and the beating induction steps of cardiac maturation, which can aid in preparing beating cardiomyocytes for regenerative medicine. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1166–1174, 2017.
Mesenchymal stem cells in the aseptic loosening of total joint replacements
Authors: Pajarinen Jukka , Lin Tzu‐hua , Nabeshima Akira , Jämsen Eemeli , Lu Laura , Nathan Karthik , Yao Zhenyu , Goodman Stuart B. 
Published: December 2016

AbstractPeri‐prosthetic osteolysis remains as the main long‐term complication of total joint replacement surgery. Research over four decades has established implant wear as the main culprit for chronic inflammation in the peri‐implant tissues and macrophages as the key cells mediating the host reaction to implant‐derived wear particles. Wear debris activated macrophages secrete inflammatory mediators that stimulate bone resorbing osteoclasts; thus bone loss in the peri‐implant tissues is increased. However, the balance of bone turnover is not only dictated by osteoclast‐mediated bone resorption but also by the formation of new bone by osteoblasts; under physiological conditions these two processes are tightly coupled. Increasing interest has been placed on the effects of wear debris on the cells of the bone‐forming lineage. These cells are derived primarily from multipotent mesenchymal stem cells (MSCs) residing in bone marrow and the walls of the microvasculature. Accumulating evidence indicates that wear debris significantly impairs MSC‐to‐osteoblast differentiation and subsequent bone formation. In this review, we summarize the current understanding of the effects of biomaterial implant wear debris on MSCs. Emerging treatment options to improve initial implant integration and treat developing osteolytic lesions by utilizing or targeting MSCs are also discussed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1195–1207, 2017.
CD31+ Cells From Peripheral Blood Facilitate Bone Regeneration in Biologically Impaired Conditions Through Combined Effects on Immunomodulation and Angiogenesis
Authors: Sass F Andrea , Schmidt-Bleek Katharina , Ellinghaus Agnes , Filter Sebastian , Rose Alexander , Preininger Bernd , Reinke Simon , Geissler Sven , Volk Hans-Dieter , Duda Georg N , Dienelt Anke 
Published: December 2016

ABSTRACT

Controlled revascularization and inflammation are key elements regulating endogenous regeneration after (bone) tissue trauma. Peripheral blood-derived cell subsets, such as regulatory T-helper cells and circulating (endothelial) progenitor cells, respectively, can support endogenous tissue healing, whereas effector T cells that are associated with an aged immune system can hinder bone regeneration. CD31 is expressed by diverse leukocytes and is well recognized as a marker of circulating endothelial (precursor) cells; however, CD31 is absent from the surface of differentiated effector T cells. Thus, we hypothesized that by separating the inhibitory fractions from the supportive fractions of circulating cells within the peripheral blood (PB) using the CD31 marker, bone regeneration in biologically compromised conditions, such as those observed in aged patients, could be improved. In support of our hypothesis, we detected an inverse correlation between CD31+ cells and effector T cells in the hematomas of human fracture patients, dependent on the age of the patient. Furthermore, we demonstrated the regenerative capacity of human PB-CD31+ cells in vitro. These findings were translated to a clinically relevant rat model of impaired bone healing. The transplantation of rat PB-CD31+ cells advanced bone tissue restoration in vivo and was associated with an early anti-inflammatory response, the stimulation of (re)vascularization, and reduced fibrosis. Interestingly, the depletion or enrichment of the highly abundant CD31+/14+ monocytes from the mixed CD31+ cell population diminished tissue regeneration at different levels, suggesting combined effects within the PB-CD31+ subsets. In summary, an intraoperative enrichment of PB-CD31+ cells might be a novel option to facilitate endogenous regeneration under biologically impaired situations by supporting immunomodulation and vascularization. © 2016 American Society for Bone and Mineral Research.
Comparison of Cytotoxic Activity in Leukemic Lineages Reveals Important Features of β‐Hairpin Antimicrobial Peptides
Authors: Buri Marcus V. , Torquato Heron F. Vieira , Barros Carlos Castilho , Ide Jaime S. , Miranda Antonio , Paredes‐Gamero Edgar J. 
Published: December 2016

ABSTRACTSeveral reports described different modes of cell death triggered by antimicrobial peptides (AMPs) due to direct effects on membrane disruption, and more recently by apoptosis and necrosis‐like patterns. Cytotoxic curves of four β‐hairpin AMPs (gomesin, protegrin, tachyplesin, and polyphemusin) were obtained from several human leukemic lineages and normal monocytes and Two cell lines were then selected based on their cytotoxic sensitivity. One was sensitive to AMPs (K562) and the other resistant (KG‐1) and their effect compared between these lineages. Thus, these lineages were chosen to further investigate biological features related with their cytotoxicities to AMPs. Stimulation with AMPs produced cell death, with activation of caspase‐3, in K562 lineage. Increase on the fluidity of plasmatic membrane by reducing cholesterol potentiated cytotoxicity of AMPs in both lineages. Quantification of internal and external gomesin binding to the cellular membrane of both K562 and KG‐1 cells showed that more peptide is accumulated inside of K562 cells. Additionally, evaluation of multi‐drug resistant pumps activity showed that KG‐1 has more activity than K562 lineage. A comparison of intrinsic gene patterns showed great differences between K562 and KG‐1, but stimulation with gomesin promoted few changes in gene expression patterns. Differences in internalization process through the plasma membrane, multidrug resistance pumps activity, and gene expression pattern are important features to AMPs regulated cell death. J. Cell. Biochem. 118: 1764–1773, 2017. © 2016 Wiley Periodicals, Inc.
Relative Impact of Risk Factors, Thwarted Belongingness, and Perceived Burdensomeness on Suicidal Ideation in Veteran Service Members
Authors: O'Connor Stephen S. , Carney Erin , Jennings Keith W. , Johnson Lora L. , Gutierrez Peter M. , Jobes David A. 
Published: December 2016

ObjectiveWe tested the associations between individualized risk factors, empirically validated constructs specific to suicide risk (i.e., thwarted belongingness and perceived burdensomeness, and two methods for conceptualizing suicidal ideation based on Suicide Index Score (SIS) and overall severity score of the Beck Scale for Suicide Ideation [BSS]).MethodThe current study included a sample of 134 suicidal Veterans who were recruited from an inpatient psychiatry unit of a Veterans Affairs Medical Center. Participants completed the BSS, Interpersonal Needs Questionnaire, Outcome Questionnaire‐45.2, Alcohol Use Disorder Identification Test, Drug Abuse Screening Test, and abbreviated versions of the Posttraumatic Stress Disorder Checklist‐Military version (PCL‐M) and Insomnia Severity Index. We used ordinary least squares regression with bootstrapping to conduct analyses due to the skewed distributions observed in the suicidal ideation outcomes.ResultsThwarted belongingness was the only statistically significant correlate of the SIS, indicating a stronger desire to be dead than alive as Veterans perceived themselves as being increasingly disconnected and isolated from others (B = 0.36, standard error [SE] = 0.01, p = 0.005). In contrast, greater overall severity scores on the BSS were associated with higher ratings on the PCL‐M (B = 0.21, SE = 0.07, p = 0.02) and for thwarted belongingness (B = 0.27, SE = 0.09, p = 0.04). Problematic alcohol use was significantly associated with lower overall severity scores (B = −.27, SE = 1.17, p < 0.001).ConclusionFindings may inform clinical strategies for conceptualizing and targeting factors associated with suicidal risk.
Integration of expression quantitative trait loci and pleiotropy identifies a novel psoriasis susceptibility gene, PTPN1
Authors: Yin Xianyong , Lin Yuan , Shen Changbing , Wang Ling , Zuo Xianbo , Zheng Xiaodong , Yang Sen , Liu Jianjun , Wilhelmsen Kirk C. , Zhang Xuejun 
Published: December 2016

AbstractBackgroundPsoriasis is a common inflammatory skin disease, whereas schizophrenia is a psychiatric disorder with substantial comorbidity. Although these two disorders manifest with apparently unrelated phenotypes, there is some evidence suggesting that they share common genetic factors.MethodsWe implemented a genetic analysis incorporating pleiotropy and annotation to genome‐wide association summary statistics data for approximately 120 000 psoriasis and schizophrenia samples, as well as whole blood expression quantitative trait loci in 5311 samples.ResultsWe observed a significant pleiotropic effect between psoriasis and schizophrenia (p = 5.92 × 10−43). We characterized an enrichment of whole blood expression quantitative trait loci in genome‐wide association data for psoriasis and schizophrenia (q1/q0 > 1.5, p < 10−77) and we revealed that common variants for both diseases were more likely to confer expression quantitative trait loci effects (q1/q0 = 4.197, SE = 0.183). Through joint analysis of the associations in the combined psoriasis and schizophrenia data set, we identified a potential susceptibility PTPN1 gene for psoriasis, which may affect the risk of psoriasis through modulation of the function of TYK2 kinase.ConclusionsThe results of the present study highlight the expression quantitative trait loci enrichment and pleiotropy in psoriasis and schizophrenia, and also suggest a possible key role of the PTPN1 gene in the etiology of psoriasis.
Learn to Play and Play to Learn: Evaluation of the One Laptop per Child Program in Costa Rica
Authors: Meza‐Cordero Jaime A. 
Published: December 2016

AbstractThe One Laptop Per Child (OLPC) initiative is one of the world's most popular interventions aiming to reduce the Information and Communication Technologies (ICTs) digital divide. Costa Rica introduced its first OLPC program in February 2012. In collaboration with the Quirós Tanzi Foundation (Foundation), implementing the program, baseline and post‐intervention information was collected from a set of 15 primary schools that were selected to be treated, and from 19 primary schools that served as a comparison group. Using a difference in difference design, this paper estimates the short‐term effects of the program on various outcomes of interest, namely: students' computer usage, time allocation and test scores. The results indicate that the program led to an increase in treated students' computer use outside of school of about 5 hours per week. Moreover, the research provides evidence that the treated students used the computer specifically to browse the internet, do homework, read and play. The research also demonstrates that the program led to a decline in the time that treated students spent on homework and outdoor activities. The research does not provide evidence to suggest that the program had an effect on participating students' school performance. Copyright © 2016 John Wiley & Sons, Ltd.
Hip MRI: Prevalence of articular cartilage defects and labral tears in asymptomatic volunteers. A comparison with a matched population of patients with femoroacetabular impingement
Authors: Tresch Florian , Dietrich Tobias J. , Pfirrmann Christian W.A. , Sutter Reto 
Published: December 2016

PurposeTo prospectively compare defects of the articular cartilage and labrum in asymptomatic volunteers and in patients with femoroacetabular impingement (FAI) matched for age and gender.Materials and MethodsThis cross‐sectional study was institutional review board approved. A total of 63 asymptomatic volunteers and 63 patients with symptomatic FAI between 20 and 50 years underwent 1.5 Tesla MRI (coronal T1‐weighted, coronal intermediate‐weighted fat saturated, transverse oblique true fast imaging with steady‐state precession [FISP], sagittal dual echo steady state [DESS] sequence). Two radiologists independently assessed defects of the cartilage and labrum at six positions. Statistics included Mann‐Whitney U‐test and Spearman's rho.ResultsA defect of the articular cartilage and/or labrum was present on average in 57% of asymptomatic volunteers, compared with 80% of symptomatic patients (P ≤ 0.028). A total of 14% of volunteers had acetabular cartilage defects, and 6% had femoral cartilage defects, compared with 47% and 30% in symptomatic patients (P ≤ 0.001 and P ≤ 0.003), respectively. Labrum defects were seen in 44% of volunteers versus 61% of patients (P ≤ 0.12). Both cartilage and labral defects were more commonly encountered in male volunteers than in female volunteers, with the largest difference seen for the acetabular cartilage (P ≤ 0.02). In all groups, the majority of cartilage and labrum defects were encountered in the anterosuperior, superior, and posterosuperior position.ConclusionA substantial number of asymptomatic volunteers had labral tears, defects of the acetabular cartilage, and to a lesser degree, defects of the femoral cartilage; our data demonstrate that not all cartilage and labral defects of the hip joint are symptomatic and that a similar predilection for location of defects is found in volunteers and FAI patients.Level of Evidence:2Technical Efficacy: Stage 3J. MAGN. RESON. IMAGING 2017;46:440–451
How warm was Britain during the Last Interglacial? A critical review of Ipswichian (MIS 5e) palaeotemperature reconstructions
Authors: Candy Ian , White Tom S. , Elias Scott 
Published: December 2016

ABSTRACTThe Last Interglacial [LIG, equivalent to marine isotope stage (MIS) 5e] was a period of enhanced global warmth, with potential significance for understanding future climate warming. It has long been proposed that the LIG in Britain (the Ipswichian Interglacial) was significantly warmer than present, based on the occurrence of fossils of extant thermophilous plant and animal species intolerant of the current climate. Here, we review the evidence for palaeotemperatures that can be derived from such fossil taxa (beetles, ostracods, plant macrofossils and herpetiles) to assess the level of warmth that Britain experienced during the LIG. Quantified palaeotemperature reconstructions generated for eight British sequences indicate that the LIG was likely to have been warmer than the present but at only one site (Trafalgar Square) is there strong evidence for climates that were significantly warmer than those experienced during the Holocene. Consequently, while there is evidence to support the idea that the thermal regime of the LIG in Britain was different from that of the Holocene, this evidence is restricted to a single site. The paper concludes by discussing the thermal regime of the LIG in Britain in the context of its role as an analogue for future warming in the 21st century and beyond.
Late readvance and rapid final deglaciation of the last ice sheet in the Grampian Mountains, Scotland
Authors: Hall Adrian M. , Binnie Steven A. , Sugden David , Dunai Tibor J. , Wood Christina 
Published: December 2016

ABSTRACTTowards the end of the last glaciation, ice sourced from the western Grampian Mountains of Scotland flowed down Strath Spey to encroach on the northern flanks of the Cairngorm Mountains. The maximum of this late advance and its subsequent retreat is recorded by moraines, ice‐marginal meltwater channels, and kame terraces that can be traced for 60 km along Strath Spey. New cosmogenic 10Be exposure ages from moraines indicate deglaciation at 15.1 ± 1.1 ka. This timing matches closely the recalibrated mean ages of 14.7 ± 0.7 and 15.2 ± 0.7 ka for the Wester Ross Readvance in the North‐West Highlands. A synchronous readvance of the British–Irish Ice Sheet (BIIS) towards the end of Greenland Stadial 2a (GS‐2a) (16.9–14.7 ka) is indicated. Thereafter active ice retreat from the flanks of Strath Spey was rapid, occurring within the ∼1 ka uncertainty of the cosmogenic exposure ages. We suggest the advance followed the collapse of the marine parts of the BIIS at ∼16 ka due to conditions of increased precipitation occurring at a time of low temperatures. The rapidity of deglaciation may reflect enhanced Föhn effects caused by the ice dome in the western Grampians.
Cave sediments constrain the latest Pleistocene advance of the Laurentide Ice Sheet in the Champlain Valley, Vermont, USA
Authors: Munroe Jeffrey S. , Perzan Zachary M. , Amidon William H. 
Published: December 2016

ABSTRACTOptically stimulated luminescence (OSL) and infrared stimulated luminescence (IRSL) dating were applied to cave sediments that were protected from the Marine Isotope Stage 2 (MIS‐2) advance of the Laurentide Ice Sheet (LIS) in the Champlain Valley of western Vermont. Evidence indicates that these sediments were derived from a subaerial landscape, requiring that the ice margin was north of the Champlain Valley when they were deposited. A basal sandy gravel was deposited during MIS‐4 (∼68 ka), sand near the middle of the composite stratigraphy was deposited during MIS‐3 (∼55 ka), and a layer of coarse sand in the stratigraphically highest position was deposited at the onset of MIS‐2 (∼35 ka). The youngest age constrains advance of the LIS south of the international border early in MIS‐2, and is combined with other available evidence to constrain ice advance rates over the 12 000 years leading up to the Last Glacial Maximum. Rates estimated from limiting ages were relatively slow (25 ma−1) as the ice ascended the adverse slope out of the St. Lawrence Lowland, increased as the margin advanced through the Champlain Valley, perhaps aided by subglacial bed deformation or ice streaming, and were fastest (∼100 ma−1) as the margin approached the terminal moraine position.
Determination of isoflavone (genistein and daidzein) concentration of soybean seed as affected by environment and management inputs
Authors: Laurenz Randy , Tumbalam Pavani , Naeve Seth , Thelen Kurt D 
Published: December 2016

AbstractBACKGROUNDIsoflavones, such as genistein and daidzein, are produced in soybean seed [Glycine max (L.) Merr.] and may be associated with health benefits in the human diet. More research is required to determine the effect of agronomic soybean treatments on isoflavone concentration. In this study from 2012 to 2014 at Michigan State University and Breckenridge locations, we have evaluated agronomic input management systems which are marketed to increase or protect potential soybean grain yield, including: nitrogen fertilization, herbicide–defoliant, foliar applied fertilizer, a biological‐based foliar application, foliar applied fungicide, foliar applied insecticide, a seed applied fungicide, and a maximized seed treatment that included fungicide and insecticide as well as an inoculant and lipo‐chitooligosaccharide nodulation promoter, for their effect on soybean seed genistein and daidzein concentrations.RESULTSPaired comparisons were made between treatments receiving a designated management input and those without the input. Year and location had a significant effect on isoflavone concentrations. Agronomic management inputs impacted soybean seed daidzein concentrations in 15 of 48 field observations and genistein concentrations in 11 of 48 observations.CONCLUSIONThe research supports findings that soybean seed isoflavone levels exhibit a location specific response, and the temporal variability experienced between years appears to influence changes in soybean isoflavone levels more than location. © 2016 Society of Chemical Industry