bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seminal cell-free DNA levels measured by PicoGreen fluorochrome are associated with sperm fertility criteria
Authors: Costa F. , Barbisan F. , Assmann C.E. , Araújo N.K.F. , de Oliveira A.R. , Signori J.P. , Rogalski F. , Bonadiman B. , Fernandes M. S. , da Cruz I.B.M. 
Published: March 2017

SummaryPrevious investigations suggested that elevated cell-free DNA (cfDNA) can indicate non-healthy states. However, the potential association between cfDNA seminal plasma levels and fertility sperm parameters has not yet been determined. Therefore, the present study evaluated the association between seminal cfDNA levels and sperm fertility criteria to determine the use of seminal cfDNA quantification. Anin vivoprotocol quantified cfDNA levels of semen samples obtained from 163 male patients using fluorescent PicoGreen dye staining. To confirm if semen cfDNA quantification is realistic, anin vitrocomplementary test was performed using three or four semen samples. The fresh sperm samples were exposed to paraquat that generates high levels of superoxide anion causing oxidative stress and cell mortality. The results showed significant association between dsDNA levels and several sperm fertility parameters, such as low viability and alterations of motility and morphology. Thein vitroanalysis confirmed the association between dsDNA levels and sperm viability. Together, these results suggest that dsDNA levels could be an important biomarker to test sperm fertility.
Effects of ghrelin on activation of Akt1 and ERK1/2 pathways duringin vitromaturation of bovine oocytes
Authors: Chouzouris Thomas-Markos , Dovolou Eleni , Krania Fotini , Pappas Ioannis S. , Dafopoulos Konstantinos , Messinis Ioannis E. , Anifandis George , Amiridis Georgios S. 
Published: March 2017

SummaryThe purpose of this study was to investigate the possible molecular pathways through which ghrelin acceleratesin vitrooocyte maturation. Bovine cumulus–oocyte complexes (COCs), after 18 or 24 h maturation in the absence or the presence of 800 pg ml–1of acylated ghrelin were either assessed for nuclear maturation or underwentin vitrofertilization in standard media and putative zygotes were culturedin vitrofor 8 days. In a subset of COCs the levels of phosphorylated Akt1 and ERK1/2 (MAPK1/3) were assessed at the 0th, 6th, 10th, 18thand 24thhours ofin vitromaturation (IVM). At 18 and 24 h no difference existed in the proportion of matured oocytes in the ghrelin-treated group, while in the control group more (P< 0.05) matured oocyte were found at 24 h. Oocyte maturation for 24 h in the presence of ghrelin resulted in substantially reduced (P< 0.05) blastocyst yield(16.3%) in comparison with that obtained after 18 h (30.0%) or to both control groups (29.3% and 26.9%, for 18 and 24 h in maturation, respectively). Ghrelin-treated oocytes expressed lower Akt1 phosphorylation rate at the 10thhour of IVM, and higher ERK1/2 at the 6thand 10thhours of IVM compared with controls. In cumulus cells, at the 18thand 24thhours of IVM Akt1 phosphorylation rate was higher in ghrelin-treated oocytes. Our results imply that ghrelin acts in a different time-dependent manner on bovine oocytes and cumulus cells modulating Akt1 and ERK1/2 phosphorylation, which brings about acceleration of the oocyte maturation process.
Base resolution maps reveal the importance of
5-hydroxymethylcytosine in a human glioblastoma
Authors: Raiber Eun-Ang , Beraldi Dario , Martínez Cuesta Sergio , McInroy Gordon R. , Kingsbury Zoya , Becq Jennifer , James Terena , Lopes Margarida , Allinson Kieren , Field Sarah , Humphray Sean , Santarius Thomas , Watts Colin , Bentley David , Balasubramanian Shankar 
Published: March 2017

AbstractAberrant genetic and epigenetic variations drive malignant transformation and are hallmarks of cancer. Using PCR-free sample preparation we achieved the first in-depth whole genome (hydroxyl)-methylcytosine, single-base-resolution maps from a glioblastoma tumour/margin sample of a patient. Our data provide new insights into how genetic and epigenetic variations are interrelated. In the tumour, global hypermethylation with a depletion of 5-hydroxymethylcytosine was observed. The majority of single nucleotide variations were identified as cytosine-to-thymine deamination products within CpG context, where cytosine was preferentially methylated in the margin. Notably, we observe that cells neighbouring tumour cells display epigenetic alterations characteristic of the tumour itself although genetically they appear “normal”. This shows the potential transfer of epigenetic information between cells that contributes to the intratumour heterogeneity of glioblastoma. Together, our reference (epi)-genome provides a human model system for future studies that aim to explore the link between genetic and epigenetic variations in cancer progression.
KCC2 downregulation facilitates epileptic seizures
Authors: Chen Lulan , Wan Li , Wu Zheng , Ren Wanting , Huang Yian , Qian Binbin , Wang Yun 
Published: March 2017

AbstractGABAA receptor-mediated inhibition depends on the maintenance of low level intracellular [Cl−] concentration, which in adult depends on neuron specific K+-Cl− cotransporter-2 (KCC2). Previous studies have shown that KCC2 was downregulated in both epileptic patients and various epileptic animal models. However, the temporal relationship between KCC2 downregulation and seizure induction is unclear yet. In this study, we explored the temporal relationship and the influence of KCC2 downregulation on seizure induction. Significant downregulation of plasma membrane KCC2 was directly associated with severe (Racine Score III and above) behavioral seizures in vivo, and occurred before epileptiform bursting activities in vitro induced by convulsant. Overexpression of KCC2 using KCC2 plasmid effectively enhanced resistance to convulsant-induced epileptiform bursting activities in vitro. Furthermore, suppression of membrane KCC2 expression, using shRNAKCC2 plasmid in vitro and shRNAKCC2 containing lentivirus in vivo, induced spontaneous epileptiform bursting activities in vitro and Racine III seizure behaviors accompanied by epileptic EEG in vivo. Our findings novelly demonstrated that altered expression of KCC2 is not the consequence of seizure occurrence but likely is the contributing factor.
Atypical sensory sensitivity as a shared feature between synaesthesia and autism
Authors: Ward Jamie , Hoadley Claire , Hughes James E. A. , Smith Paula , Allison Carrie , Baron-Cohen Simon , Simner Julia 
Published: March 2017

AbstractSeveral studies have suggested that there is a link between synaesthesia and autism but the nature of that link remains poorly characterised. The present study considers whether atypical sensory sensitivity may be a common link between the conditions. Sensory hypersensitivity (aversion to certain sounds, touch, etc., or increased ability to make sensory discriminations) and/or hyposensitivity (desire to stimulate the senses , or a reduced response to sensory stimuli are a recently introduced diagnostic feature of autism spectrum conditions (ASC). Synaesthesia is defined by unusual sensory experiences and has also been linked to a typical cortical hyper-excitability. The Glasgow Sensory Questionnaire (GSQ) was administered to synaesthetes and people with ASC. Both groups reported increased sensory sensitivity relative to controls with a large effect size. Both groups also reported a similar pattern of both increased hyper- and hypo-sensitivities across multiple senses. The AQ (Autism-Spectrum Quotient) scores were elevated in the synaesthetes, and one subscale of this measure (attention to detail) placed synaesthetes within the autistic range. A standard laboratory test of visual stress (the Pattern Glare Test), administered online, corroborated the findings of increased sensitivity to aversive visual stimuli in synaesthetes. We conclude that atypical sensory sensitivity is an important shared feature between autism and synaesthesia.
Partial delignification of wood and membrane preparation using a quaternary ammonium ionic liquid
Authors: Miao Jiaojiao , Yu Yongqi , Jiang Zeming , Tang Lan , Zhang Liping 
Published: March 2017

AbstractThis work determined that southern yellow pine wood can almost be completely dissolved in the quaternary ammonium ionic liquid tetrabutylammonium acetate with dimethyl sulfoxide (in a 2:8 mass ratio), after minimal grinding, upon heating at 85 °C for three dissolution/reconstitution cycles, each 1.5 h. Approximately 34.6% of the native lignin and 67.4% of the native carbohydrates present in the original wood can subsequently be extracted, respectively, and were assessed. A gradual decrease in lignin with increased extraction cycles resulted in increased crystallinity index of the cellulose II in the cellulose-rich residue, as confirmed by X-ray diffraction. An increasingly homogeneous macrostructure in the cellulose-rich residue was also evident from scanning electron microscopy images. Membranes cast directly from either wood or cellulose-rich residue solutions in the same tetrabutylammonium acetate/dimethyl sulfoxide system, were prepared using a papermaking-like process. Morphological and mechanical studies indicated that lignin extraction made the membranes more uniform and flexible. Systematic increases in the fibril lengths and orientations of the recovered materials were also found with decreasing lignin contents on the basis of atomic force microscopy analysis. This work demonstrates that relatively efficient partial separation of pine wood and subsequent membrane preparation are possible using a quaternary ammonium ionic liquid.
Theta-alpha EEG phase distributions in the frontal area for dissociation of visual and auditory working memory
Authors: Akiyama Masakazu , Tero Atsushi , Kawasaki Masahiro , Nishiura Yasumasa , Yamaguchi Yoko 
Published: March 2017

AbstractWorking memory (WM) is known to be associated with synchronization of the theta and alpha bands observed in electroencephalograms (EEGs). Although frontal-posterior global theta synchronization appears in modality-specific WM, local theta synchronization in frontal regions has been found in modality-independent WM. How frontal theta oscillations separately synchronize with task-relevant sensory brain areas remains an open question. Here, we focused on theta-alpha phase relationships in frontal areas using EEG, and then verified their functional roles with mathematical models. EEG data showed that the relationship between theta (6 Hz) and alpha (12 Hz) phases in the frontal areas was about 1:2 during both auditory and visual WM, and that the phase distributions between auditory and visual WM were different. Next, we used the differences in phase distributions to construct FitzHugh-Nagumo type mathematical models. The results replicated the modality-specific branching by orthogonally of the trigonometric functions for theta and alpha oscillations. Furthermore, mathematical and experimental results were consistent with regards to the phase relationships and amplitudes observed in frontal and sensory areas. These results indicate the important role that different phase distributions of theta and alpha oscillations have in modality-specific dissociation in the brain.
Altered Topological Properties of Brain Networks in Social Anxiety Disorder: A Resting-state Functional MRI Study
Authors: Zhu Hongru , Qiu Changjian , Meng Yajing , Yuan Minlan , Zhang Yan , Ren Zhengjia , Li Yuchen , Huang Xiaoqi , Gong Qiyong , Lui Su , Zhang Wei 
Published: March 2017

AbstractRecent studies involving connectome analysis including graph theory have yielded potential biomarkers for mental disorders. In this study, we aimed to investigate the differences of resting-state network between patients with social anxiety disorder (SAD) and healthy controls (HCs), as well as to distinguish between individual subjects using topological properties. In total, 42 SAD patients and the same number of HCs underwent resting functional MRI, and the topological organization of the whole-brain functional network was calculated using graph theory. Compared with the controls, the patients showed a decrease in 49 positive connections. In the topological analysis, the patients showed an increase in the area under the curve (AUC) of the global shortest path length of the network (Lp) and a decrease in the AUC of the global clustering coefficient of the network (Cp). Furthermore, the AUCs of Lp and Cp were used to effectively discriminate the individual SAD patients from the HCs with high accuracy. This study revealed that the neural networks of the SAD patients showed changes in topological characteristics, and these changes were prominent not only in both groups but also at the individual level. This study provides a new perspective for the identification of patients with SAD.
A multi-component classifier for nonalcoholic fatty liver disease (NAFLD) based on genomic, proteomic, and phenomic data domains
Authors: Wood G. Craig , Chu Xin , Argyropoulos George , Benotti Peter , Rolston David , Mirshahi Tooraj , Petrick Anthony , Gabrielson John , Carey David J. , DiStefano Johanna K. , Still Christopher D. , Gerhard Glenn S. 
Published: March 2017

AbstractNon-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions that include steatohepatitis and fibrosis that are thought to emanate from hepatic steatosis. Few robust biomarkers or diagnostic tests have been developed for hepatic steatosis in the setting of obesity. We have developed a multi-component classifier for hepatic steatosis comprised of phenotypic, genomic, and proteomic variables using data from 576 adults with extreme obesity who underwent bariatric surgery and intra-operative liver biopsy. Using a 443 patient training set, protein biomarker discovery was performed using the highly multiplexed SOMAscan® proteomic assay, a set of 19 clinical variables, and the steatosis predisposing PNPLA3 rs738409 single nucleotide polymorphism genotype status. The most stable markers were selected using a stability selection algorithm with a L1-regularized logistic regression kernel and were then fitted with logistic regression models to classify steatosis, that were then tested against a 133 sample blinded verification set. The highest area under the ROC curve (AUC) for steatosis of PNPLA3 rs738409 genotype, 8 proteins, or 19 phenotypic variables was 0.913, whereas the final classifier that included variables from all three domains had an AUC of 0.935. These data indicate that multi-domain modeling has better predictive power than comprehensive analysis of variables from a single domain.
ZYZ-168 alleviates cardiac fibrosis after myocardial infarction through inhibition of ERK1/2-dependent ROCK1 activation
Authors: Luo Shanshan , Hieu Tran Ba , Ma Fenfen , Yu Ying , Cao Zhonglian , Wang Minjun , Wu Weijun , Mao Yicheng , Rose Peter , Law Betty Yuen-Kwan , Zhu Yi Zhun 
Published: March 2017

AbstractSelective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α–smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9). These were related with decreased phosphorylation of ERK1/2 and expression of Rho-associated coiled-coil containing protein kinase 1 (ROCK1). In cardiac fibroblasts stimulated with TGF-β1, phenotypic switches of cardiac fibroblasts to myofibroblasts were observed. Inhibition of ERK1/2 phosphorylation or knockdown of ROCK1 expectedly reduced TGF-β1 induced fibrotic responses. ZYZ-168 appeared to inhibit the fibrotic responses in a concentration dependent manner, in part via a decrease in ROCK 1 expression through inhibition of the phosphorylation status of ERK1/2. For inhibition of ERK1/2 phosphorylation with a specific inhibitor reduced the activation of ROCK1. Considering its anti-apoptosis activity in MI, ZYZ-168 may be a potential drug candidate for treatment of MI-induced cardiac fibrosis.
Applying torque to the Escherichia coli flagellar motor using magnetic tweezers
Authors: van Oene Maarten M. , Dickinson Laura E. , Cross Bronwen , Pedaci Francesco , Lipfert Jan , Dekker Nynke H. 
Published: March 2017

AbstractThe bacterial flagellar motor of Escherichia coli is a nanoscale rotary engine essential for bacterial propulsion. Studies on the power output of single motors rely on the measurement of motor torque and rotation under external load. Here, we investigate the use of magnetic tweezers, which in principle allow the application and active control of a calibrated load torque, to study single flagellar motors in Escherichia coli. We manipulate the external load on the motor by adjusting the magnetic field experienced by a magnetic bead linked to the motor, and we probe the motor’s response. A simple model describes the average motor speed over the entire range of applied fields. We extract the motor torque at stall and find it to be similar to the motor torque at drag-limited speed. In addition, use of the magnetic tweezers allows us to force motor rotation in both forward and backward directions. We monitor the motor’s performance before and after periods of forced rotation and observe no destructive effects on the motor. Our experiments show how magnetic tweezers can provide active and fast control of the external load while also exposing remaining challenges in calibration. Through their non-invasive character and straightforward parallelization, magnetic tweezers provide an attractive platform to study nanoscale rotary motors at the single-motor level.
Elucidation of terpenoid metabolism in Scoparia dulcis by RNA-seq analysis
Authors: Yamamura Yoshimi , Kurosaki Fumiya , Lee Jung-Bum 
Published: March 2017

AbstractScoparia dulcis biosynthesize bioactive diterpenes, such as scopadulcic acid B (SDB), which are known for their unique molecular skeleton. Although the biosynthesis of bioactive diterpenes is catalyzed by a sequence of class II and class I diterpene synthases (diTPSs), the mechanisms underlying this process are yet to be fully identified. To elucidate these biosynthetic machinery, we performed a high-throughput RNA-seq analysis, and de novo assembly of clean reads revealed 46,332 unique transcripts and 40,503 two unigenes. We found diTPSs genes including a putative syn-copalyl diphosphate synthase (SdCPS2) and two kaurene synthase-like (SdKSLs) genes. Besides them, total 79 full-length of cytochrome P450 (CYP450) genes were also discovered. The expression analyses showed selected CYP450s associated with their expression pattern of SdCPS2 and SdKSL1, suggesting that CYP450 candidates involved diterpene modification. SdCPS2 represents the first predicted gene to produce syn-copalyl diphosphate in dicots. In addition, SdKSL1 potentially contributes to the SDB biosynthetic pathway. Therefore, these identified genes associated with diterpene biosynthesis lead to the development of genetic engineering focus on diterpene metabolism in S. dulcis.
Ethylene-induced transcriptional and hormonal responses at the onset of sugarcane ripening
Authors: Cunha Camila P. , Roberto Guilherme G. , Vicentini Renato , Lembke Carolina G. , Souza Glaucia M. , Ribeiro Rafael V. , Machado Eduardo C. , Lagôa Ana M. M. A. , Menossi Marcelo 
Published: March 2017

AbstractThe effects of ethephon as a sugarcane ripener are attributed to ethylene. However, the role of this phytohormone at the molecular level is unknown. We performed a transcriptome analysis combined with the evaluation of sucrose metabolism and hormone profiling of sugarcane plants sprayed with ethephon or aminoethoxyvinylglycine (AVG), an ethylene inhibitor, at the onset of ripening. The differential response between ethephon and AVG on sucrose level and sucrose synthase activity in internodes indicates ethylene as a potential regulator of sink strength. The correlation between hormone levels and transcriptional changes suggests ethylene as a trigger of multiple hormone signal cascades, with approximately 18% of differentially expressed genes involved in hormone biosynthesis, metabolism, signalling, and response. A defence response elicited in leaves favoured salicylic acid over the ethylene/jasmonic acid pathway, while the upper internode was prone to respond to ethylene with strong stimuli on ethylene biosynthesis and signalling genes. Besides, ethylene acted synergistically with abscisic acid, another ripening factor, and antagonistically with gibberellin and auxin. We identified potential ethylene target genes and characterized the hormonal status during ripening, providing insights into the action of ethylene at the site of sucrose accumulation. A molecular model of ethylene interplay with other hormones is proposed.
Improved Bioavailability and Antitumor Effect of Docetaxel by TPGS Modified Proniosomes: In Vitro and In Vivo Evaluations
Authors: Liu Helong , Tu Liangxing , Zhou Yongxin , Dang Zefang , Wang Luting , Du Junfeng , Feng Jianfang , Hu Kaili 
Published: March 2017

AbstractA novel oral drug delivery system, TPGS modified docetaxel proniosomes (DTX-TPGS-PNs), was designed to enhance the oral bioavailability and antitumor efficiency of the poorly water-soluble drug docetaxel. DTX-TPGS-PN niosomes were 93 ± 6.5 nm in size, −18.53 ± 1.65 mV in zeta potential and exhibited spherical morphology, with an encapsulation efficiency of 97.31 ± 0.60%. The system showed sustained release in both simulated gastric and intestinal fluid. The results of caco-2 monolayer, everted gut sac model and improved single-pass intestinal perfusion model transport studies showed that DTX-TPGS-PN niosomes could significantly improve the absorption of DTX. The pharmacokinetics study suggested the absolute bioavailability of DTX-TPGS-PN niosomes were 7.3 times that of DTX solution. In addition, a higher antitumor efficacy than DTX solution was demonstrated in MCF-7 and MDA-MB-231 cells in vitro and in MCF-7 tumor-bearing mice model in vivo. Our results demonstrated DTX-TPGS-PN is promising in enhancing the bioavailability and efficiency of poorly water-soluble drug DTX, and the potential of proniosomes as stable precursors for oral drug delivery.
Catch-and-Release of Target Cells Using Aptamer-Conjugated Electroactive Zwitterionic Oligopeptide SAM
Authors: Enomoto Junko , Kageyama Tatsuto , Osaki Tatsuya , Bonalumi Flavia , Marchese Francesca , Gautieri Alfonso , Bianchi Elena , Dubini Gabriele , Arrigoni Chiara , Moretti Matteo , Fukuda Junji 
Published: March 2017

AbstractNucleic acid aptamers possess attractive features such as specific molecular recognition, high-affinity binding, and rapid acquisition and replication, which could be feasible components for separating specific cells from other cell types. This study demonstrates that aptamers conjugated to an oligopeptide self-assembled monolayer (SAM) can be used to selectively trap human hepatic cancer cells from cell mixtures containing normal human hepatocytes or human fibroblasts. Molecular dynamics calculations have been performed to understand how the configurations of the aptamers are related to the experimental results of selective cell capture. We further demonstrate that the captured hepatic cancer cells can be detached and collected along with electrochemical desorption of the oligopeptide SAM, and by repeating these catch-and-release processes, target cells can be enriched. This combination of capture with aptamers and detachment with electrochemical reactions is a promising tool in various research fields ranging from basic cancer research to tissue engineering applications.