bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats
Authors: Zalfa Cristina , Rota Nodari Laura , Vacchi Elena , Gelati Maurizio , Profico Daniela , Boido Marina , Binda Elena , De Filippis Lidia , Copetti Massimiliano , Garlatti Valentina , Daniele Paola , Rosati Jessica , De Luca Alessandro , Pinos Francesca , Cajola Laura , Visioli Alberto , Mazzini Letizia , Vercelli Alessandro , Svelto Maria , Vescovi Angelo Luigi , Ferrari Daniela 
Published: April 2019

AbstractStem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS.
Enhanced osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis: a study based on a three-dimensional biomimetic environment
Authors: Zheng Guan , Xie Zhongyu , Wang Peng , Li Jinteng , Li Ming , Cen Shuizhong , Tang Su’an , Liu Wenjie , Ye Guiwen , Li Yuxi , Wang Shan , Wu Xiaohua , Su Hongjun , Wu Yanfeng , Shen Huiyong 
Published: April 2019

AbstractThe mechanism of pathological osteogenesis in Ankylosing spondylitis (AS) is largely unknown. Our previous studies demonstrated that the imbalance between BMP-2 and Noggin secretion induces abnormal osteogenic differentiation of marrow-derived mesenchymal stem cells (MSCs) from AS patients in a two-dimensional culture environment. In this study, HA/β-TCP scaffolds were further used as a three-dimensional (3D) biomimetic culture system to mimic the bone microenvironment in vivo to determine the abnormal osteogenic differentiation of AS-MSCs. We demonstrated that when cultured in HA/β-TCP scaffolds, AS-MSCs had a stronger osteogenic differentiation capacity than that of MSCs from healthy donors (HD-MSCs) in vitro and in vivo. This dysfunction resulted from BMP2 overexpression in AS-MSCs, which excessively activated the Smad1/5/8 and ERK signalling pathways and finally led to enhanced osteogenic differentiation. Both the signalling pathway inhibitors and siRNAs inhibiting BMP2 expression could rectify the enhanced osteogenic differentiation of AS-MSCs. Furthermore, BMP2 expression in ossifying entheses was significantly higher in AS patients. In summary, our study demonstrated that AS-MSCs possess enhanced osteogenic differentiation in HA/β-TCP scaffolds as a 3D biomimetic microenvironment because of BMP2 overexpression, but not Noggin. These results provide insights into the mechanism of pathological osteogenesis, which can aid in the development of niche-targeting medications for AS.
Testing the influence of habitat experienced during the natal phase on habitat selection later in life in Scandinavian wolves
Authors: Milleret Cyril , Ordiz Andrés , Sanz-Pérez Ana , Uzal Antonio , Carricondo-Sanchez David , Eriksen Ane , Sand Håkan , Wabakken Petter , Wikenros Camilla , Åkesson Mikael , Zimmermann Barbara 
Published: April 2019

AbstractNatal habitat preference induction (NHPI) occurs when characteristics of the natal habitat influence the future habitat selection of an animal. However, the influence of NHPI after the dispersal phase has received remarkably little attention. We tested whether exposure to humans in the natal habitat helps understand why some adult wolves Canis lupus may approach human settlements more than other conspecifics, a question of both ecological and management interest. We quantified habitat selection patterns within home ranges using resource selection functions and GPS data from 21 wolf pairs in Scandinavia. We identified the natal territory of each wolf with genetic parental assignment, and we used human-related characteristics within the natal territory to estimate the degree of anthropogenic influence in the early life of each wolf. When the female of the adult wolf pair was born in an area with a high degree of anthropogenic influence, the wolf pair tended to select areas further away from humans, compared to wolf pairs from natal territories with a low degree of anthropogenic influence. Yet the pattern was statistically weak, we suggest that our methodological approach can be useful in other systems to better understand NHPI and to inform management about human-wildlife interactions.
Chitosan-based hydrogel to support the paracrine activity of mesenchymal stem cells in spinal cord injury treatment
Authors: Boido M. , Ghibaudi M. , Gentile P. , Favaro E. , Fusaro R. , Tonda-Turo C. 
Published: April 2019

AbstractAdvanced therapies which combine cells with biomaterial-based carriers are recognized as an emerging and powerful method to treat challenging diseases, such as spinal cord injury (SCI). By enhancing transplanted cell survival and grafting, biomimetic hydrogels can be properly engineered to encapsulate cells and locate them at the injured site in a minimally invasive way. In this work, chitosan (CS) based hydrogels were developed to host mesenchymal stem cells (MSCs), since their paracrine action can therapeutically enhance the SC regeneration, limiting the formation of a glial scar and reducing cell death at the injured site. An injectable and highly permeable CS-based hydrogel was fabricated having a rapid gelation upon temperature increase from 0 to 37 °C. CS was selected as former material both for its high biocompatibility that guarantees the proper environment for MSCs survival and for its ability to provide anti-inflammatory and anti-oxidant cues. MSCs were mixed with the hydrogel solution prior to gelation. MSC viability was not affected by the CS hydrogel and encapsulated MSCs were able to release MSC-vesicles as well as to maintain their anti-oxidant features. Finally, preliminaryin vivotests on SCI mice revealed good handling of the CS solution loading MSCs during implantation and high encapsulated MSCs survival after 7 days.
Driven gyrotropic skyrmion motion through steps in magnetic anisotropy
Authors: Zhou Yifan , Mansell Rhodri , van Dijken Sebastiaan 
Published: April 2019

AbstractThe discovery of magnetic skyrmions in ultrathin heterostructures has led to great interest in possible applications in memory and logic devices. The non-trivial topology of magnetic skyrmions gives rise to a gyrotropic motion, where, under an applied energy gradient a skyrmion gains a component of motion perpendicular to the applied force. So far, device proposals have largely neglected this motion or treated it as a barrier to correct operation. Here, we show that skyrmions can be efficiently moved perpendicular to an energy step created by local changes in the perpendicular magnetic anisotropy. We propose an experimentally-realizable skyrmion racetrack device which uses voltage-controlled magnetic anisotropy to induce a step in magnetic anisotropy and drive a skyrmion unidirectionally using alternating voltage pulses.
The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair
Authors: Guard Steven E. , Poss Zachary C. , Ebmeier Christopher C. , Pagratis Maria , Simpson Helen , Taatjes Dylan J. , Old William M. 
Published: April 2019

AbstractThe chromosome 21 encoded protein kinase DYRK1A is essential for normal human development. Mutations in DYRK1A underlie a spectrum of human developmental disorders, and increased dosage in trisomy 21 is implicated in Down syndrome related pathologies. DYRK1A regulates a diverse array of cellular processes through physical interactions with substrates and binding partners in various subcellular compartments. Despite recent large-scale protein-protein interaction profiling efforts, DYRK1A interactions specific to different subcellular compartments remain largely unknown, impeding progress toward understanding emerging roles for this kinase. Here, we used immunoaffinity purification and quantitative mass spectrometry to identify nuclear interaction partners of endogenous DYRK1A. This interactome was enriched in DNA damage repair factors, transcriptional elongation factors and E3 ubiquitin ligases. We validated an interaction with RNF169, a factor that promotes homology directed repair upon DNA damage, and found that DYRK1A expression and kinase activity are required for maintenance of 53BP1 expression and subsequent recruitment to DNA damage loci. Further, DYRK1A knock out conferred resistance to ionizing radiation in colony formation assays, suggesting that DYRK1A expression decreases cell survival efficiency in response to DNA damage and points to a tumor suppressive role for this kinase.
A Biotransformation Process for Production of Genistein from Sophoricoside by a Strain of Rhizopus oryza
Authors: Mei Jianfeng , Chen Xiang , Liu Jianghua , Yi Yu , Zhang Yanlu , Ying Guoqing 
Published: April 2019

AbstractGenistein is known to have multiple biological activities and has great potential for use as a preventative medicine and in disease treatment. Genistein can be extracted from plants, but also can be obtained from its glycoside form, sophoricoside, which is more abundant in some plants. Biotransformation by unpurified microbial enzymes has the advantage of low cost and is a preferred method for production of natural compounds. This study isolated a strain of Rhizopus oryzae that could produce β-glucosidase, which efficiently hydrolyzes sophoricoside into genistein, from an enrichment culture of the dried fruits of Sophora japonica. After the composition of enzyme-producing medium and biotransformation conditions were optimized, a genistein yield of 85.6% was obtained after 24 h in a shake-flask biotransformation at pH 7.0 using an initial substrate concentration of 1 g/L. The developed process provides an alternative method for production of genistein, and would be suitable for scale-up production in the pharmaceutical industry.
The risk of selenium deficiency in Malawi is large and varies over multiple spatial scales
Authors: Phiri Felix P. , Ander E. Louise , Bailey Elizabeth H. , Chilima Benson , Chilimba Allan D. C. , Gondwe Jellita , Joy Edward J. M. , Kalimbira Alexander A. , Kumssa Diriba B. , Lark R. Murray , Phuka John C. , Salter Andrew , Suchdev Parminder S. , Watts Michael J. , Young Scott D. , Broadley Martin R. 
Published: April 2019

AbstractSelenium (Se) is an essential human micronutrient. Deficiency of Se decreases the activity of selenoproteins and can compromise immune and thyroid function and cognitive development, and increase risks from non-communicable diseases. The prevalence of Se deficiency is unknown in many countries, especially in sub-Saharan Africa (SSA). Here we report that the risk of Se deficiency in Malawi is large among a nationally representative population of 2,761 people. For example, 62.5% and 29.6% of women of reproductive age (WRA, n = 802) had plasma Se concentrations below the thresholds for the optimal activity of the selenoproteins glutathione peroxidase 3 (GPx3; <86.9 ng mL−1) and iodothyronine deiodinase (IDI; <64.8 ng mL−1), respectively. This is the first nationally representative evidence of widespread Se deficiency in SSA. Geostatistical modelling shows that Se deficiency risks are influenced by soil type, and also by proximity to Lake Malawi where more fish is likely to be consumed. Selenium deficiency should be quantified more widely in existing national micronutrient surveillance programmes in SSA given the marginal additional cost this would incur.
Association of resting heart rate and its change with incident cardiovascular events in the middle-aged and older Chinese
Authors: Tian Jing , Yuan Yu , Shen Miaoyan , Zhang Xiaomin , He Meian , Guo Huan , Yang Handong , Wu Tangchun 
Published: April 2019

AbstractWhether heart rate change is associated with cardiovascular disease (CVD) in the general population is unclear. We conducted a prospective cohort study to assess the association of resting heart rate and its change with incident CVD in the middle-aged and older Chinese. Resting heart rate was measured during the baseline survey (September 2008 to June 2010) and the resurvey (2013). Incident CVD was followed up until December 31, 2016. Finally, a total of 20,828 participants were included in the analyses of baseline heart rate and 9132 participants were included in the analyses of heart rate change. The associations of baseline heart rate and heart rate change with incident CVD were assessed with multivariable Cox proportional hazards models. Compared with moderate baseline heart rate (65 to 80 bpm), low baseline heart rate (<65 bpm) was associated with higher risk of CVD (HR, 1.19; 95% CI, 1.07–1.32). Compared with stable heart rate (−5 to 15 bpm) in the moderate baseline heart rate group (65 to 80 bpm), an increase of heart rate (>15 bpm) in high baseline heart rate group (>80 bpm) (HR, 1.67; 95% CI, 1.02–2.71) or a decrease of heart rate (<−5 bpm) in low baseline heart rate group (<65 bpm) (HR, 2.48; 95% CI, 1.27–4.82) was associated with higher risk of CVD. In conclusion, low resting heart rate is associated with higher risk of CVD. Both continuous increase in high baseline heart rate and decrease in low baseline heart rate are associated with higher risk of CVD.
Monte Carlo investigation of the characteristics of radioactive beams for heavy ion therapy
Authors: Chacon Andrew , Safavi-Naeini Mitra , Bolst David , Guatelli Susanna , Franklin Daniel R. , Iwao Yuma , Akamatsu Go , Tashima Hideaki , Yoshida Eiji , Nishikido Fumihiko , Kitagawa Atsushi , Mohammadi Akram , Gregoire Marie-Claude , Yamaya Taiga , Rosenfeld Anatoly B. 
Published: April 2019

AbstractThis work presents a simulation study evaluating relative biological effectiveness at 10% survival fraction (RBE10) of several different positron-emitting radionuclides in heavy ion treatment systems, and comparing these to the RBE10s of their non-radioactive counterparts. RBE10 is evaluated as a function of depth for three positron-emitting radioactive ion beams (10C, 11C and 15O) and two stable ion beams (12C and 16O) using the modified microdosimetric kinetic model (MKM) in a heterogeneous skull phantom subject to a rectangular 50 mm × 50 mm × 60 mm spread out Bragg peak. We demonstrate that the RBE10 of the positron-emitting radioactive beams is almost identical to the corresponding stable isotopes. The potential improvement in PET quality assurance image quality which is obtained when using radioactive beams is evaluated by comparing the signal to background ratios of positron annihilations at different intra- and post-irradiation time points. Finally, the incidental dose to the patient resulting from the use of radioactive beams is also quantified and shown to be negligible.
Sulfenamide and Sulfonamide Derivatives of Metformin – A New Option to Improve Endothelial Function and Plasma Haemostasis
Authors: Markowicz-Piasecka Magdalena , Huttunen Kristiina M. , Broncel Marlena , Sikora Joanna 
Published: April 2019

AbstractType 2 diabetes mellitus (T2DM) is a multi-factorial disease which can cause multiple organ dysfunction, including that of the vascular endothelium. The aim of the present study was to evaluate the effects of metformin, and its sulfenamide and sulfonamide derivatives (compounds 1–8) on the selected markers of endothelial function and blood coagulation. The integrity of endothelial cells(ECs) was examined using the real-time cell electric impedance system. Tissue Factor(TF) production, the release of von Willebrand Factor (vWF) and tissue plasminogen activator(t-PA) from ECs were determined using immunoenzymatic assays, while the process of platelet thrombus formation using the Total Thrombus-Formation Analysis System. Sulfenamide with n-butyl alkyl chain(3) does not interfere with ECs integrity, and viability (nCI(24h) = 1.03 ± 0.03 vs. 1.06 ± 0.11 for control), but possesses anticoagulation properties manifested by prolonged platelet-dependent thrombus formation (Occlusion Time 370.3 ± 77.0 s vs. 286.7 ± 65.5 s for control) in semi-physiological conditions. Both p- and o-nitro-benzenesulfonamides (compounds7,8) exhibit anti-coagulant properties demonstrated by decreased vWF release and prolonged parameters of platelet thrombus formation and total blood thrombogenicity. In conclusion, chemical modification of metformin scaffold into sulfenamides or sulfonamides might be regarded as a good starting point for the design and synthesis of novel biguanide-based compounds with anticoagulant properties and valuable features regarding endothelial function.
High-throughput sequencing reveals the diversity and community structure of rhizosphere fungi of Ferula Sinkiangensis at different soil depths
Authors: Zhang Tao , Wang Zhongke , Lv Xinhua , Li Yang , Zhuang Li 
Published: April 2019

AbstractFerula sinkiangesis is a valuable medicinal plant that has become endangered. Improving the soil habitat of Ferula sinkiangesis can alleviate plant damage. Fungi play an important role in the soil, but current information on the fungal community structure in the habitat of Ferula sinkiangesis and the relationship between soil fungi and abiotic factors remains unclear. In this study, we analyzed the relative abundance of fungal species in the rhizosphere of Ferula sinkiangesis. Spearman correlation analysis showed that the abiotic factor total potassium (TK) significantly explained the alpha diversity of the fungal community. At altitude, available phosphorus (AP), nitrate nitrogen (NN) and TK were significantly associated with the fungal species. In addition, a two-way ANOVA showed that soil depth had no significant effects on the alpha diversity of rhizosphere and non-rhizosphere fungi. Interestingly, linear discriminant effect size (LEfSe) analysis indicated that different biomarkers were present at varying soil depths. These findings may be related to the growth and medicinal properties of Ferula Sinkiangensis.
Physiological and pathological impact of AQP1 knockout in mice
Authors: Hua Ying , Ying Xinxin , Qian Yiyu , Liu Haibin , Lan Yehui , Xie Ailan , Zhu Xueqiong 
Published: April 2019

Abstract
Aquaporin 1 (AQP1) is a glycoprotein responsible for water passive transport quickly across biological membrane. Here, we reviewed the structural and functional impacts of AQP1 knockout (AQP1-KO) in animal or cell culture models. AQP1 gene deletion can cause a large number of abnormalities including the disturbance in epithelial fluid secretion, polyhydramnios, deficiency of urinary concentrating function, and impairment of pain perception. AQP1-KO mice also displayed aberrations of cardiovascular, gastrointestinal and hepatobiliary, and kidney functions as well as placenta and embryo development. Moreover, AQP1-KO perturbed tumor angiogenesis and led to reduced brain injury upon trauma. On the cellular level, AQP1-KO caused neuroinflammation, aberrant cell proliferation and migration, and macrophages infiltration. Mechanistic studies confirmed that AQP1 gene products regulate the secretory function and participated in balancing the osmotic water flux across the peritoneal membrane. The available data indicated that AQP1 might serve as a potential target for developing novel therapeutic approaches against diverse human diseases.
Reliability and Validity of a Korean Version of the Tinnitus Primary Function Questionnaire
Authors: Shin Jinbae , Heo Sohee , Lee Ho-Ki , Tyler Richard , Jin In-Ki 
Published: April 2019

Purpose
The aim of this study was to evaluate the reliability and validity of a Korean version of the Tinnitus Primary Function Questionnaire (K-TPFQ).

Method

A total of 79 subjects participated in the study. All participants completed the K-TPFQ, and the Korean versions of the Pittsburgh Sleep Quality Index (
Buysse, Reynolds, Monk, Berman, & Kupfer, 1989
;
Sohn, Kim, Lee, & Cho, 2012
), the Beck Depression Inventory (
Beck, Ward, Mendelson, Mock, & Erbaugh, 1961
;
Jo, Park, Jo, Ryu, & Han, 2007
), the State-Trait Anxiety Inventory questionnaire (
Cho & Choi, 1989
;
Spielberger & Gorsuch, 1983
), and the Tinnitus Handicap Questionnaire (
Kuk, Tyler, Russell, & Jordan, 1990
).

Results
The K-TPFQ exhibited good or high internal consistency and reliability (Cronbach's alpha range: .91–.95, item-total correlation range: .50–.82). The total score derived from the items of the K-TPFQ and its subcategories was moderately correlated with that of questionnaires that measure similar parameters (Pearson correlation coefficient range: .50–.79).

Conclusions
Overall, the results of this study indicate that the K-TPFQ is reliable and valid. Therefore, the current translated version of the K-TPFQ is applicable to subjects with Korean as their 1st language and proves to be a useful tinnitus questionnaire.
Differentiating Beyond Name Agreement for Picture Naming: Insight From Age-Related Selection Deficits
Authors: Madden Daniel L. , Sale Martin V. , Robinson Gail A. 
Published: April 2019

Purpose
Pictures consistently referred to by the same name (high agreement) are named faster than pictures that elicit inconsistent responses across individuals (low agreement). Although this effect is more pronounced in older adults apparently due to slower lexical selection, it is unclear whether this is consistent for different types of low agreement pictures. We investigated whether pictures with different sources of disagreement have differing selection requirements, as indexed by naming latencies.

Method
Picture naming latencies were compared for 20 young (ages 18–35 years) and 20 older adults (ages 60–80 years) across 3 object naming conditions: high name agreement, low name agreement due to multiple correct names, and low agreement due to abbreviations and elaborations.

Results

Compared to high agreement items, responses were slower specifically for low agreement items with multiple names, and to a lesser extent, items with abbreviations and elaborations (
p
< .001). Older adults were slower than younger adults, especially for low agreement items with abbreviations and elaborations (
p
= .031).

Conclusions
Our findings indicate differential lexical selection requirements for low agreement pictures, depending on the reason for agreement being low. This demonstrates the importance of differentiating the source of disagreement in any experimental or clinical assessment of picture naming.