bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical developmental trajectory of local spontaneous brain activity in autism spectrum disorder
Authors: Guo Xiaonan , Chen Heng , Long Zhiliang , Duan Xujun , Zhang Youxue , Chen Huafu 
Published: January 2017

AbstractAutism spectrum disorder (ASD) is marked by atypical trajectory of brain maturation, yet the developmental abnormalities in brain function remain unclear. The current study examined the effect of age on amplitude of low-frequency fluctuations (ALFF) in ASD and typical controls (TC) using a cross-sectional design. We classified all the participants into three age cohorts: child (<11 years, 18ASD/20TC), adolescent (11–18 years, 28ASD/26TC) and adult (≥18 years, 18ASD/18TC). Two-way analysis of variance (ANOVA) was performed to ascertain main effects and interaction effects on whole brain ALFF maps. Results exhibited significant main effect of diagnosis in ASD with decreased ALFF in the right precuneus and left middle occipital gyrus during all developmental stages. Significant diagnosis-by-age interaction was observed in the medial prefrontal cortex (mPFC) with ALFF lowered in autistic children but highered in autistic adolescents and adults. Specifically, remarkable quadratic change of ALFF with increasing age in mPFC presented in TC group was absent in ASD. Additionally, abnormal ALFF values in diagnosis-related brain regions predicted the social deficits in ASD. Our findings indicated aberrant developmental patterns of spontaneous brain activity associated with social deficits in ASD and highlight the crucial role of the default mode network in the development of disease.
A novel role for the DNA repair gene Rad51 in Netrin-1 signalling
Authors: Glendining K. A. , Markie D. , Gardner R. J. M. , Franz E. A. , Robertson S. P. , Jasoni C. L. 
Published: January 2017

AbstractMutations in RAD51 have recently been linked to human Congenital Mirror Movements (CMM), a developmental disorder of the motor system. The only gene previously linked to CMM encodes the Netrin-1 receptor DCC, which is important for formation of corticospinal and callosal axon tracts. Thus, we hypothesised that Rad51 has a novel role in Netrin-1-mediated axon development. In mouse primary motor cortex neurons, Rad51 protein was redistributed distally down the axon in response to Netrin-1, further suggesting a functional link between the two. We next manipulated Rad51 expression, and assessed Netrin-1 responsiveness. Rad51 siRNA knockdown exaggerated Netrin-1-mediated neurite branching and filopodia formation. RAD51 overexpression inhibited these responses, whereas overexpression of the CMM-linked R250Q mutation, a predicted loss-of-function, had no effect. Thus, Rad51 appears to negatively regulate Netrin-1 signalling. Finally, we examined whether Rad51 might operate by modulating the expression of the Unc5 family, known negative regulators of Netrin-1-responsiveness. Unc5b and Unc5c transcripts were downregulated in response to Rad51 knockdown, and upregulated with RAD51 overexpression, but not R250Q. Thus, Rad51 negatively regulates Netrin-1 signalling, at least in part, by modulating the expression of Unc5s. Imbalance of positive and negative influences is likely to lead to aberrant motor system development resulting in CMMs.
A simple and rapid flow cytometry-based assay to identify a competent embryo prior to embryo transfer
Authors: Pallinger Eva , Bognar Zoltan , Bodis Jozsef , Csabai Timea , Farkas Nelli , Godony Krisztina , Varnagy Akos , Buzas Edit , Szekeres-Bartho Julia 
Published: January 2017

AbstractMultiple pregnancy is a risk for prematurity and preterm birth. The goal of assisted reproduction is to achieve a single pregnancy, by transferring a single embryo. This requires improved methods to identify the competent embryo. Here, we describe such a test, based on flow cytometric determination of the nucleic acid (PI+) containing extracellular vesicle (EV) count in day 5 embryo culture media. 88 women undergoing IVF were included in the study. More than 1 embryos were transferred to most patients. In 58 women, the transfer resulted in clinical pregnancy, whereas in 30 women in implantation failure. In 112 culture media of embryos from the “clinical pregnancy” group, the number of PI+ EVs was significantly lower than in those of 49 embryos, from the “implantation failure” group. In 14 women, transfer of a single embryo resulted in a singleton pregnancy, or, transfer of two embryos in twin pregnancy. The culture media of 19 out of the 20 “confirmed competent” embryos contained a lower level of PI+ EVs than the cut off level, suggesting that the competent embryo can indeed be identified by low PI+ EV counts. We developed a noninvasive, simple, inexpensive, quick test, which identifies the embryos that are most likely to implant.
Dysregulation of WTI (−KTS) is Associated with the Kidney-Specific Effects of the LMX1B R246Q Mutation
Authors: Hall Gentzon , Lane Brandon , Chryst-Ladd Megan , Wu Guanghong , Lin Jen-Jar , Qin XueJun , Hauser Elizabeth R. , Gbadegesin Rasheed 
Published: January 2017

AbstractMutations in the LIM homeobox transcription factor 1-beta (LMX1B) are a cause of nail patellar syndrome, a condition characterized by skeletal changes, glaucoma and focal segmental glomerulosclerosis. Recently, a missense mutation (R246Q) in LMX1B was reported as a cause of glomerular pathologies without extra-renal manifestations, otherwise known as nail patella-like renal disease (NPLRD). We have identified two additional NPLRD families with the R246Q mutation, though the mechanisms by which LMX1BR246Q causes a renal-specific phenotype is unknown. In this study, using human podocyte cell lines overexpressing either myc-LMX1BWT or myc-LMX1BR246Q, we observed dominant negative and haploinsufficiency effects of the mutation on the expression of podocyte genes such as NPHS1, GLEPP1, and WT1. Specifically, we observed a novel LMX1BR246Q-mediated downregulation of WT1(−KTS) isoforms in podocytes. In conclusion, we have shown that the renal-specific phenotype associated with the LMX1BR246Q mutation may be due to a dominant negative effect on WT1(−KTS) isoforms that may cause a disruption of the WT1 (−KTS):(+KTS) isoform ratio and a decrease in the expression of podocyte genes. Full delineation of the LMX1B gene regulon is needed to define its role in maintenance of glomerular filtration barrier integrity.
Nonreciprocal Transverse Photonic Spin and Magnetization-Induced Electromagnetic Spin-Orbit Coupling
Authors: Levy Miguel , Karki Dolendra 
Published: January 2017

AbstractWe present a formulation of electromagnetic spin-orbit coupling in magneto-optic media, and propose an alternative source of spin-orbit coupling to non-paraxial optics vortices. Our treatment puts forth a formulation of nonreciprocal transverse-spin angular-momentum-density shifts for evanescent waves in magneto-optic waveguide media. It shows that magnetization-induced electromagnetic spin-orbit coupling is possible, and that it leads to unequal spin to orbital angular momentum conversion in magneto-optic media evanescent waves in opposite propagation-directions. Generation of free-space helicoidal beams based on this conversion is shown to be spin-helicity- and magnetization-dependent. We show that transverse-spin to orbital angular momentum coupling into magneto-optic waveguide media engenders spin-helicity-dependent unidirectional propagation. This unidirectional effect produces different orbital angular momenta in opposite directions upon excitation-spin-helicity reversals.
C-terminus of HSC70-Interacting Protein (CHIP) Inhibits Adipocyte Differentiation via Ubiquitin- and Proteasome-Mediated Degradation of PPARγ
Authors: Kim Jung-Hoon , Shin Soyeon , Seo Jinho , Lee Eun-Woo , Jeong Manhyung , Lee Min-sik , Han Hyun-Ji , Song Jaewhan 
Published: January 2017

AbstractPPARγ (Peroxisome proliferator-activated receptor γ) is a nuclear receptor involved in lipid homeostasis and related metabolic diseases. Acting as a transcription factor, PPARγ is a master regulator for adipocyte differentiation. Here, we reveal that CHIP (C-terminus of HSC70-interacting protein) suppresses adipocyte differentiation by functioning as an E3 ligase of PPARγ. CHIP directly binds to and induces ubiquitylation of the PPARγ protein, leading to proteasome-dependent degradation. Stable overexpression or knockdown of CHIP inhibited or promoted adipogenesis, respectively, in 3T3-L1 cells. On the other hand, a CHIP mutant defective in E3 ligase could neither regulate PPARγ protein levels nor suppress adipogenesis, indicating the importance of CHIP-mediated ubiquitylation of PPARγ in adipocyte differentiation. Lastly, a CHIP null embryo fibroblast exhibited augmented adipocyte differentiation with increases in PPARγ and its target protein levels. In conclusion, CHIP acts as an E3 ligase of PPARγ, suppressing PPARγ-mediated adipogenesis.
Prediction of N-Methyl-D-Aspartate Receptor GluN1-Ligand Binding Affinity by a Novel SVM-Pose/SVM-Score Combinatorial Ensemble Docking Scheme
Authors: Leong Max K. , Syu Ren-Guei , Ding Yi-Lung , Weng Ching-Feng 
Published: January 2017

AbstractThe glycine-binding site of the N-methyl-D-aspartate receptor (NMDAR) subunit GluN1 is a potential pharmacological target for neurodegenerative disorders. A novel combinatorial ensemble docking scheme using ligand and protein conformation ensembles and customized support vector machine (SVM)-based models to select the docked pose and to predict the docking score was generated for predicting the NMDAR GluN1-ligand binding affinity. The predicted root mean square deviation (RMSD) values in pose by SVM-Pose models were found to be in good agreement with the observed values (n = 30, r2 = 0.928–0.988, "Equation missing" = 0.894–0.954, RMSE = 0.002–0.412, s = 0.001–0.214), and the predicted pKi values by SVM-Score were found to be in good agreement with the observed values for the training samples (n = 24, r2 = 0.967, "Equation missing" = 0.899, RMSE = 0.295, s = 0.170) and test samples (n = 13, q2 = 0.894, RMSE = 0.437, s = 0.202). When subjected to various statistical validations, the developed SVM-Pose and SVM-Score models consistently met the most stringent criteria. A mock test asserted the predictivity of this novel docking scheme. Collectively, this accurate novel combinatorial ensemble docking scheme can be used to predict the NMDAR GluN1-ligand binding affinity for facilitating drug discovery.
Triglyceride to HDL-C Ratio is Associated with Insulin Resistance in Overweight and Obese Children
Authors: Iwani Nur Ahmad Kamil Zati , Jalaludin Muhammad Yazid , Zin Ruziana Mona Wan Mohd , Fuziah Md Zain , Hong Janet Yeow Hua , Abqariyah Yahya , Mokhtar Abdul Halim , Wan Nazaimoon Wan Mohamud 
Published: January 2017

AbstractThe purpose of this study was to investigate the usefulness of triglyceride to hdl-c ratio (TG:HDL-C) as an insulin resistance (IR) marker for overweight and obese children. A total of 271 blood samples of obese and overweight children aged 9–16 years were analysed for fasting glucose, lipids and insulin. Children were divided into IR and non-insulin resistance, using homeostasis model assessment (HOMA). The children were then stratified by tertiles of TG: HDL-C ratio. The strength between TG:HDL-C ratio and other parameters of IR were quantified using Pearson correlation coefficient (r). Odds ratio was estimated using multiple logistic regression adjusted for age, gender, pubertal stages and IR potential risk factors. Children with IR had significantly higher TG:HDL-C ratio (2.48) (p = 0.01). TG:HDL-C ratio was significantly correlated with HOMA-IR (r = 0.104, p < 0.005) and waist circumference (r = 0.134, p < 0.001). Increasing tertiles of TG:HDL-C ratio showed significant increase in mean insulin level (p = 0.03), HOMA-IR (p = 0.04) and significantly higher number of children with acanthosis nigricans and metabolic syndrome. The odds of having IR was about 2.5 times higher (OR = 2.47; 95% CI 1.23, 4.95; p = 0.01) for those in the highest tertiles of TG:HDL-C ratio. Hence, TG:HDL-C may be a useful tool to identify high risk individuals.
Enhancement of mosquito trapping efficiency by using pulse width modulated light emitting diodes
Authors: Liu Yu-Nan , Liu Yu-Jen , Chen Yi-Chian , Ma Hsin-Yi , Lee Hsiao-Yi 
Published: January 2017

AbstractIn this study, a light-driving bug zapper is presented for well controlling the diseases brought by insects, such as mosquitoes. In order to have the device efficient to trap the insect pests in off-grid areas, pulse width modulated light emitting diodes (PWM-LED) combined with a solar power module are proposed and implemented. With specific PWM electric signals to drive the LED, it is found that no matter what the ability of catching insects or the consumed power efficiency can be enhanced thus. It is demonstrated that 40% of the UV LED consumed power and 25.9% of the total load power consumption can be saved, and the trapped mosquitoes are about 250% increased when the PWM method is applied in the bug zapper experiments.
Ultra-sensitive Pressure sensor based on guided straight mechanical cracks
Authors: Choi Yong Whan , Kang Daeshik , Pikhitsa Peter V. , Lee Taemin , Kim Sang Moon , Lee Gunhee , Tahk Dongha , Choi Mansoo 
Published: January 2017

AbstractRecently, a mechanical crack-based strain sensor with high sensitivity was proposed by producing free cracks via bending metal coated film with a known curvature. To further enhance sensitivity and controllability, a guided crack formation is needed. Herein, we demonstrate such a ultra-sensitive sensor based on the guided formation of straight mechanical cracks. The sensor has patterned holes on the surface of the device, which concentrate the stress near patterned holes leading to generate uniform cracks connecting the holes throughout the surface. We found that such a guided straight crack formation resulted in an exponential dependence of the resistance against the strain, overriding known linear or power law dependences. Consequently, the sensors are highly sensitive to pressure (with a sensitivity of over 1 × 105 at pressures of 8–9.5 kPa range) as well as strain (with a gauge factor of over 2 × 106 at strains of 0–10% range). A new theoretical model for the guided crack system has been suggested to be in a good agreement with experiments. Durability and reproducibility have been also confirmed.
Establishment of an accurate and fast detection method using molecular beacons in loop-mediated isothermal amplification assay
Authors: Liu Wei , Huang Simo , Liu Ningwei , Dong Derong , Yang Zhan , Tang Yue , Ma Wen , He Xiaoming , Ao Da , Xu Yaqing , Zou Dayang , Huang Liuyu 
Published: January 2017

AbstractThis study established a constant-temperature fluorescence quantitative detection method, combining loop-mediated isothermal amplification (LAMP) with molecular beacons. The advantages of LAMP are its convenience and efficiency, as it does not require a thermocycler and results are easily visualized by the naked eye. However, a major disadvantage of current LAMP techniques is the use of indirect evaluation methods (e.g., electrophoresis, SYBR Green I dye, precipitation, hydroxynaphthol blue dye, the turbidimetric method, calcein/Mn2+ dye, and the composite probe method), which cannot distinguish between the desired products and products of nonspecific amplification, thereby leading to false positives. Use of molecular beacons avoids this problem because molecular beacons produce fluorescence signals only when binding to target DNA, thus acting as a direct indicator of amplification products. Our analyses determined the optimal conditions for molecular beacons as an evaluation tool in LAMP: beacon length of 25–45 bp, beacon concentration of 0.6–1 pmol/μL, and reaction temperature of 60–65 °C. In conclusion, we validated a novel molecular beacon loop-mediated isothermal amplification method (MB-LAMP), realizing the direct detection of LAMP product.
Predictive screening of M1 and M2 macrophages reveals the immunomodulatory effectiveness of post spinal cord injury azithromycin treatment
Authors: Gensel John C. , Kopper Timothy J. , Zhang Bei , Orr Michael B. , Bailey William M. 
Published: January 2017

AbstractSpinal cord injury (SCI) triggers a heterogeneous macrophage response that when experimentally polarized toward alternative forms of activation (M2 macrophages) promotes tissue and functional recovery. There are limited pharmacological therapies that can drive this reparative inflammatory state. In the current study, we used in vitro systems to comprehensively defined markers of macrophages with known pathological (M1) and reparative (M2) properties in SCI. We then used these markers to objectively define the macrophage activation states after SCI in response to delayed azithromycin treatment. Mice were subjected to moderate-severe thoracic contusion SCI. Azithromycin or vehicle was administered beginning 30 minutes post-SCI and then daily for 3 or 7 days post injury (dpi). We detected a dose-dependent polarization toward purportedly protective M2 macrophages with daily AZM treatment. Specifically, AZM doses of 10, 40, or 160 mg/kg decreased M1 macrophage gene expression at 3 dpi while the lowest (10 mg/kg) and highest (160 mg/kg) doses increased M2 macrophage gene expression at 7 dpi. Azithromycin has documented immunomodulatory properties and is commonly prescribed to treat infections in SCI individuals. This work demonstrates the utility of objective, comprehensive macrophage gene profiling for evaluating immunomodulatory SCI therapies and highlights azithromycin as a promising agent for SCI treatment.
Polymorphisms in Telomere Length Associated TERC and TERT predispose for Ischemic Stroke in a Chinese Han population
Authors: Zhang Shuo , Ji Guofa , Liang Yiqian , Zhang Rui , Shi Puyu , Guo Dangshe , Li Chunqi , Feng Jing , Liu Feng , Peng Rong , Chen Mingwei 
Published: January 2017

AbstractThe role of telomere in genomic stability is an established fact. Variation in leukocyte telomere length (LTL) has been considered a crucial factor that associated with age-associated diseases. To elucidate the association between LTL variation and ischemic stroke (IS) risk, we selected ten single nucleotide polymorphisms (SNPs) in three genes (TERC, TERT and RTEL1) that previously reported link to LTL, and genotyped SNPs of these genes in a case-control study. The association between polymorphisms and IS risk were tested by Chi squared test and haplotype analysis. In allele association analysis, allele “C” in rs10936599 of TERC gene and allele “G” in rs2853677 of TERT gene were found to have an increased risk of IS when compared with allele “T” and “A”, respectively. Model association analysis showed that genotype “G/A” in the overdominant model and genotypes “G/A” and “A/A” in the dominant model of rs2242652 presented a more likelihood to have IS. Another TERT locus (rs2853677) with genotype “G” was also found IS-related risky in the log-additive model. Taken together, our results suggest a potential association between LTL related TERC, TERT gene variants and ischemic stroke risk.
Sea-level rise induced amplification of coastal protection design heights
Authors: Arns Arne , Dangendorf Sönke , Jensen Jürgen , Talke Stefan , Bender Jens , Pattiaratchi Charitha 
Published: January 2017

AbstractCoastal protection design heights typically consider the superimposed effects of tides, surges, waves, and relative sea-level rise (SLR), neglecting non-linear feedbacks between these forcing factors. Here, we use hydrodynamic modelling and multivariate statistics to show that shallow coastal areas are extremely sensitive to changing non-linear interactions between individual components caused by SLR. As sea-level increases, the depth-limitation of waves relaxes, resulting in waves with larger periods, greater amplitudes, and higher run-up; moreover, depth and frictional changes affect tide, surge, and wave characteristics, altering the relative importance of other risk factors. Consequently, sea-level driven changes in wave characteristics, and to a lesser extent, tides, amplify the resulting design heights by an average of 48–56%, relative to design changes caused by SLR alone. Since many of the world’s most vulnerable coastlines are impacted by depth-limited waves, our results suggest that the overall influence of SLR may be greatly underestimated in many regions.
An Integrated Miniature Bioprocessing for Personalized Human Induced Pluripotent Stem Cell Expansion and Differentiation into Neural Stem Cells
Authors: Lin Haishuang , Li Qiang , Lei Yuguo 
Published: January 2017

AbstractHuman induced pluripotent stem cells (iPSCs) are ideal cell sources for personalized cell therapies since they can be expanded to generate large numbers of cells and differentiated into presumably all the cell types of the human body in vitro. In addition, patient specific iPSC-derived cells induce minimal or no immune response in vivo. However, with current cell culture technologies and bioprocessing, the cost for biomanufacturing clinical-grade patient specific iPSCs and their derivatives are very high and not affordable for majority of patients. In this paper, we explored the use of closed and miniature cell culture device for biomanufacturing patient specific neural stem cells (NSCs) from iPSCs. We demonstrated that, with the assist of a thermoreversible hydrogel scaffold, the bioprocessing including iPSC expansion, iPSC differentiation into NSCs, the subsequent depletion of undifferentiated iPSCs from the NSCs, and concentrating and transporting the purified NSCs to the surgery room, could be integrated and completed within two closed 15 ml conical tubes.
Mean Platelet Volume and Arterial Stiffness – Clinical Relationship and Common Genetic Variability
Authors: Panova-Noeva Marina , Arnold Natalie , Hermanns M. Iris , Prochaska Jürgen H. , Schulz Andreas , Spronk Henri M. , Binder Harald , Pfeiffer Norbert , Beutel Manfred , Blankenberg Stefan , Zeller Tanja , Lotz Johannes , Münzel Thomas , Lackner Karl J. , ten Cate Hugo , Wild Philipp S. 
Published: January 2017

AbstractVessel wall stiffening is an important clinical parameter, but it is unknown whether platelets, key elements in the pathogenesis of arterial thrombosis, are associated with arterial stiffness. The present studies sought to determine whether mean platelet volume (MPV), a potential marker of platelet activation, is linked to vascular elasticity as assessed by the augmentation index (AIx), in 15,010 individuals from the population-based Gutenberg Health Study. Multivariable analysis showed that MPV in both males (β 0.776; 95thCI [0.250;1.16]; p = 0.0024) and females (β 0.881[0.328;1.43]; p = 0.0018) is strongly associated with AIx. Individuals with MPV and AIx above the sex-specific medians had worse survival. Association analysis between MPV-related genetic variants and arterial stiffness identified four genetic variants in males and one in females related with AIx. Cox regression analysis for mortality identified one of these joint genetic variants close to ring finger protein 145 gene (RNF145, rs10076782) linked with increased mortality (hazard ratio 2.02; 95thCI [1.35;3.02]; p = 0.00061). Thus, these population-based data demonstrate a close relation between platelet volume as a potential marker of platelet activation and arterial stiffness in both sexes. Further research is warranted to further elucidate the mechanisms underlying larger platelets‘ role in arterial stiffening including the role of shared common genetics.