bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase
Authors: Srivastava Jitendra Kumar , Pillai Girinath G. , Bhat Hans Raj , Verma Amita , Singh Udaya Pratap 
Published: July 2017

AbstractA novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Dawley rats. The effect of anti-breast cancer effect of 7l was quantified on the basis of tumour incidence, body weight and tumor volume in DMBA-induced rats. Its effect on biochemical parameters, such as antioxidant status (SOD, CAT, GPX and GSH) and lipid peroxidation was also studied. The compound 7l showed inhibition of EGFR downstream signalling in the western blot analysis.
CrossCheck: an open-source web tool for high-throughput screen data analysis
Authors: Najafov Jamil , Najafov Ayaz 
Published: July 2017

AbstractModern high-throughput screening methods allow researchers to generate large datasets that potentially contain important biological information. However, oftentimes, picking relevant hits from such screens and generating testable hypotheses requires training in bioinformatics and the skills to efficiently perform database mining. There are currently no tools available to general public that allow users to cross-reference their screen datasets with published screen datasets. To this end, we developed CrossCheck, an online platform for high-throughput screen data analysis. CrossCheck is a centralized database that allows effortless comparison of the user-entered list of gene symbols with 16,231 published datasets. These datasets include published data from genome-wide RNAi and CRISPR screens, interactome proteomics and phosphoproteomics screens, cancer mutation databases, low-throughput studies of major cell signaling mediators, such as kinases, E3 ubiquitin ligases and phosphatases, and gene ontological information. Moreover, CrossCheck includes a novel database of predicted protein kinase substrates, which was developed using proteome-wide consensus motif searches. CrossCheck dramatically simplifies high-throughput screen data analysis and enables researchers to dig deep into the published literature and streamline data-driven hypothesis generation. CrossCheck is freely accessible as a web-based application at http://proteinguru.com/crosscheck.
Mapping resistance responses to Sclerotinia infestation in introgression lines of Brassica juncea carrying genomic segments from wild Brassicaceae B. fruticulosa
Authors: Rana Kusum , Atri Chhaya , Gupta Mehak , Akhatar Javed , Sandhu Prabhjodh S. , Kumar Nitin , Jaswal Ravinder , Barbetti Martin J. , Banga Surinder S. 
Published: July 2017

AbstractSclerotinia stem rot (Sclerotinia sclerotiorum) is a major disease of Brassica oilseeds. As suitable donors to develop resistant cultivars are not available in crop Brassicas, we introgressed resistance from a wild Brassicaceae species, B. fruticulosa. We produced 206 B. juncea-B. fruticulosa introgression lines (ILs). These were assessed for pollen grain fertility, genome size variations and resistance responses to Sclerotinia following stem inoculations under disease-conducive conditions. Of these, 115 ILs showing normal fertility and genome size were selected for cytogenetic characterization using florescent genomic in situ hybridization (Fl-GISH). B. fruticulosa segment substitutions were indicated in 28 ILs. These were predominantly terminal and located on B-genome chromosomes. A final set of 93 highly fertile and euploid (2n = 36) ILs were repeat-evaluated for their resistance responses during 2014–15. They were also genotyped with 202 transferable and 60 candidate gene SSRs. Association mapping allowed detection of ten significant marker trait associations (MTAs) after Bonferroni correction. These were: CNU-m157-2, RA2G05, CNU-m353-3, CNU-m442-5, ACMP00454-2, ACMP00454-3, EIN2-3-1, M641-1, Na10D09-1 and Na10D11-1. This is the first time such a molecular mapping technique has been deployed with introgression lines carrying genomic segments from B. fruticulosa, and the first to show that they possess high levels of resistance against S. sclerotiorum.
Benchmarking selected computational gene network growing tools in context of virus-host interactions
Authors: Taye Biruhalem , Vaz Candida , Tanavde Vivek , Kuznetsov Vladimir A. , Eisenhaber Frank , Sugrue Richard J. , Maurer-Stroh Sebastian 
Published: July 2017

AbstractSeveral available online tools provide network growing functions where an algorithm utilizing different data sources suggests additional genes/proteins that should connect an input gene set into functionally meaningful networks. Using the well-studied system of influenza host interactions, we compare the network growing function of two free tools GeneMANIA and STRING and the commercial IPA for their performance of recovering known influenza A virus host factors previously identified from siRNA screens. The result showed that given small (~30 genes) or medium (~150 genes) input sets all three network growing tools detect significantly more known host factors than random human genes with STRING overall performing strongest. Extending the networks with all the three tools significantly improved the detection of GO biological processes of known host factors compared to not growing networks. Interestingly, the rate of identification of true host factors using computational network growing is equal or better to doing another experimental siRNA screening study which could also be true and applied to other biological pathways/processes.
Investigating glycemic potential of rice by unraveling compositional variations in mature grain and starch mobilization patterns during seed germination
Authors: Guzman Maria Krishna de , Parween Sabiha , Butardo Vito M. , Alhambra Crisline Mae , Anacleto Roslen , Seiler Christiane , Bird Anthony R. , Chow Chung-Ping , Sreenivasulu Nese 
Published: July 2017

AbstractRice lines with slower starch digestibility provide opportunities in mitigating the global rise in type II diabetes and related non-communicable diseases. However, screening for low glycemic index (GI) in rice breeding programs is not possible due to time and cost constraints. This study evaluated the feasibility of using in vitro cooked grain amylolysis, starch mobilization patterns during seed germination, and variation in starch structure and composition in the mature seed to differentiate patterns of starch digestibility. Mobilization patterns of total starch, resistant starch, amylose and amylopectin chains, and free sugars during seed germination revealed that the process is analogous to digestion in the human gastrointestinal tract. The combination of these biochemical markers can be used as an alternative measure to predict GI. Additionally, transcriptome analysis of stored mRNA transcripts in high and low GI lines detected differences in starch metabolism and confirmed the importance of seed storage pathways in influencing digestibility. Pathway analyses supported by metabolomics data revealed that resistant starch, cell wall non-starch polysaccharides and flavonoids potentially contribute to slower digestibility. These new insights can guide precision breeding programs to produce low GI rice with acceptable cooking quality to help mitigate the burden of diet-associated lifestyle diseases.
Classification of skin phenotypes caused by diabetes mellitus using complex scattering parameters in the millimeter-wave frequency range
Authors: Dornuf Fabian , Martín-Mateos Pedro , Duarte Blanca , Hils Bernhard , Bonilla-Manrique Oscar Elias , Larcher Fernando , Acedo Pablo , Krozer Viktor 
Published: July 2017

AbstractThe pathological skin phenotype caused by hyperglycemia is an important indicator for the progress of diabetes mellitus. An early detection of diabetes assures an early intervention to regulate the carbohydrate metabolism. In this publication a non-invasive detection principle based on the measurement of complex scattering parameters in the millimeter-wave frequency range is presented. The measurement principle provides evidence of the applicability for the identification of different glycemic states in animal models. The method proposed here can be used to predict diabetes status in animal models and is interesting for application on humans in view of safeness of millimeter-wave radiation. Furthermore the complex scattering parameters give important information about the anatomic varieties between the analyzed skin samples of the different mice strains. In contrast to other methods, our approach is less sensitive to skin variations between animals.
Monolithically-Integrated TE-mode 1D Silicon-on-Insulator Isolators using Seedlayer-Free Garnet
Authors: Zhang Cui , Dulal Prabesh , Stadler Bethanie J. H. , Hutchings David C. 
Published: July 2017

AbstractThe first experimental TE-mode silicon-on-insulator (SOI) isolators using Faraday Rotation are here realized to fill the ‘missing link’ in source-integrated near infrared photonic circuits. The isolators are simple 1D 2-element waveguides, where garnet claddings and longitudinal magnetic fields produce nonreciprocal mode conversion, the waveguide equivalent of Faraday Rotation (FR). Quasi-phase matched claddings are used to overcome the limitations of birefringence. Current experimental SOI isolators use nonreciprocal phase shift (NRPS) in interferometers or ring resonators, but to date NRPS requires TM-modes, so the TE-modes normally produced by integrated lasers cannot be isolated without many ancillary polarisation controls. The presented FR isolators are made via lithography and sputter deposition, which allows facile upscaling compared to the pulsed laser deposition or wafer bonding used in the fabrication of NRPS devices. Here, isolation ratios and losses of 11 dB and 4 dB were obtained, and future designs are identified capable of isolation ratios >30 dB with losses <6 dB.
Opposite, bidirectional shifts in excitation and inhibition in specific types of dorsal horn interneurons are associated with spasticity and pain post-SCI
Authors: Kopach Olga , Medvediev Volodymyr , Krotov Volodymyr , Borisyuk Anya , Tsymbaliuk Vitaliy , Voitenko Nana 
Published: July 2017

AbstractSpasticity, a common complication after spinal cord injury (SCI), is frequently accompanied by chronic pain. The physiological origin of this pain (critical to its treatment) remains unknown, although spastic motor dysfunction has been related to the hyperexcitability of motoneurons and to changes in spinal sensory processing. Here we show that the pain mechanism involves changes in sensory circuits of the dorsal horn (DH) where nociceptive inputs integrate for pain processing. Spasticity is associated with the DH hyperexcitability resulting from an increase in excitation and disinhibition occurring in two respective types of sensory interneurons. In the tonic-firing inhibitory lamina II interneurons, glutamatergic drive was reduced while glycinergic inhibition was potentiated. In contrast, excitatory drive was boosted to the adapting-firing excitatory lamina II interneurons while GABAergic and glycinergic inhibition were reduced. Thus, increased activity of excitatory DH interneurons coupled with the reduced excitability of inhibitory DH interneurons post-SCI could provide a neurophysiological mechanism of central sensitization and chronic pain associated with spasticity.
Neuronal imaging with ultrahigh dynamic range multiphoton microscopy
Authors: Yang Ruohui , Weber Timothy D. , Witkowski Ellen D. , Davison Ian G. , Mertz Jerome 
Published: July 2017

AbstractMultiphoton microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. We present a digital electronic add-on technique that vastly improves the dynamic range of a multiphoton microscope while limiting potential photodamage. The add-on provides real-time negative feedback to regulate the laser power delivered to the sample, and a log representation of the sample strength to accommodate ultrahigh dynamic range without loss of information. No microscope hardware modifications are required, making the technique readily compatible with commercial instruments. Benefits are shown in both structural and in-vivo functional mouse brain imaging applications.
Diastolic Augmentation Index Improves Radial Augmentation Index in Assessing Arterial Stiffness
Authors: Yao Yang , Hao Liling , Xu Lisheng , Zhang Yahui , Qi Lin , Sun Yingxian , Yang Benqiang , van de Vosse Frans N. , Yao Yudong 
Published: July 2017

AbstractArterial stiffness is an important risk factor for cardiovascular events. Radial augmentation index (AI
r
) can be more conveniently measured compared with carotid-femoral pulse wave velocity (cfPWV). However, the performance of AI
r
in assessing arterial stiffness is limited. This study proposes a novel index AI
rd
, a combination of AI
r
and diastolic augmentation index (AI
d
) with a weight α, to achieve better performance over AI
r
in assessing arterial stiffness. 120 subjects (43 ± 21 years old) were enrolled. The best-fit α is determined by the best correlation coefficient between AI
rd
and cfPWV. The performance of the method was tested using the 12-fold cross validation method. AI
rd
(r = 0.68, P < 0.001) shows a stronger correlation with cfPWV and a narrower prediction interval than AI
r
(r = 0.61, P < 0.001), AI
d
(r = −0.17, P = 0.06), the central augmentation index (AI
c
) (r = 0.61, P < 0.001) or AI
c
normalized for heart rate of 75 bpm (r = 0.65, P < 0.001). Compared with AI
r
(age, P < 0.001; gender, P < 0.001; heart rate, P < 0.001; diastolic blood pressure, P < 0.001; weight, P = 0.001), AI
rd
has fewer confounding factors (age, P < 0.001; gender, P < 0.001). In conclusion, AI
rd
derives performance improvement in assessing arterial stiffness, with a stronger correlation with cfPWV and fewer confounding factors.
Increased neural noise and impaired brain synchronization in fibromyalgia patients during cognitive interference
Authors: González-Villar A. J. , Samartin-Veiga N. , Arias M. , Carrillo-de-la-Peña M. T. 
Published: July 2017

AbstractFibromyalgia (FM) and other chronic pain syndromes are associated with cognitive dysfunction and attentional deficits, but the neural basis of such alterations is poorly understood. Dyscognition may be related to high levels of neural noise, understood as increased random electrical fluctuations that impair neural communication; however, this hypothesis has not yet been tested in any chronic pain condition. Here we compared electroencephalographic activity (EEG) in 18 FM patients -with high self-reported levels of cognitive dysfunction- and 22 controls during a cognitive control task. We considered the slope of the Power Spectrum Density (PSD) as an indicator of neural noise. As the PSD slope is flatter in noisier systems, we expected to see shallower slopes in the EEG of FM patients. Higher levels of neural noise should be accompanied by reduced power modulation and reduced synchronization between distant brain locations after stimulus presentation. As expected, FM patients showed flatter PSD slopes. After applying a Laplacian spatial filter, we found reduced theta and alpha power modulation and reduced midfrontal-posterior theta phase synchronization. Results suggest higher neural noise and impaired local and distant neural coordination in the patients and support the neural noise hypothesis to explain dyscognition in FM.
Highly selective tungstate transporter protein TupA from Desulfovibrio alaskensis G20
Authors: Otrelo-Cardoso Ana Rita , Nair Rashmi R. , Correia Márcia A. S. , Cordeiro Raquel S. Correia , Panjkovich Alejandro , Svergun Dmitri I. , Santos-Silva Teresa , Rivas Maria G. 
Published: July 2017

AbstractMolybdenum and tungsten are taken up by bacteria and archaea as their soluble oxyanions through high affinity transport systems belonging to the ATP-binding cassette (ABC) transporters. The component A (ModA/TupA) of these transporters is the first selection gate from which the cell differentiates between MoO42−, WO42− and other similar oxyanions. We report the biochemical characterization and the crystal structure of the apo-TupA from Desulfovibrio desulfuricans G20, at 1.4 Å resolution. Small Angle X-ray Scattering data suggests that the protein adopts a closed and more stable conformation upon ion binding. The role of the arginine 118 in the selectivity of the oxyanion was also investigated and three mutants were constructed: R118K, R118E and R118Q. Isothermal titration calorimetry clearly shows the relevance of this residue for metal discrimination and oxyanion binding. In this sense, the three variants lost the ability to coordinate molybdate and the R118K mutant keeps an extremely high affinity for tungstate. These results contribute to an understanding of the metal-protein interaction, making it a suitable candidate for a recognition element of a biosensor for tungsten detection.
Genetic differentiation of the Schizothorax species complex (Cyprinidae) in the Nujiang River (upper Salween)
Authors: Chen Weitao , Yue Xingjian , He Shunping 
Published: July 2017

AbstractPhenotypically diverse species from recently evolved groups always share allele/haplotype due to insufficient differentiation in the early process. In this study, we performed population genetics analyses using sequences from the mitochondrial cytochromebgene, and two nuclear genes to investigate the genetic differentiation of the closely relatedSchizothoraxspecies complex, comprising a group of alpine fish living in the Nujiang River. The results from both mtDNA and nDNA markers revealed relatively low but pronounced genetic differentiation among the threeSchizothoraxspecies, i.e.,Schizothorax gongshanensis,S.lissolabiatus, andS.nukiangensis. However, haplotype sharing was frequently occurred among the three species. Divergence time estimation suggested the last glaciation on the Tibetan Plateau (0.075–0.01 Ma) might drive the divergence of the species complex. Gene flow might contribute to the haplotype sharing betweenS.gongshanensisandS.lissolabiatus, and betweenS.gongshanensisandS.nukiangensis, whereas retention of ancestral polymorphisms seemed to be a better explanation of the haplotype sharing betweenS.lissolabiatusandS.nukiangensis. In addition,S.lissolabiatuspopulations should obtain more protection in the future because of their low genetic diversity and habitat fragmentation. In summary, our study assesses genetic differentiation among the three closely relatedSchizothoraxspecies and explores the possible driving forces for their differentiation.
Prediction of presynaptic and postsynaptic neurotoxins by combining various Chou’s pseudo components
Authors: Huo Haiyan , Li Tao , Wang Shiyuan , Lv Yingli , Zuo Yongchun , Yang Lei 
Published: July 2017

AbstractPresynaptic and postsynaptic neurotoxins are two groups of neurotoxins. Identification of presynaptic and postsynaptic neurotoxins is an important work for numerous newly found toxins. It is both costly and time consuming to determine these two neurotoxins by experimental methods. As a complement, using computational methods for predicting presynaptic and postsynaptic neurotoxins could provide some useful information in a timely manner. In this study, we described four algorithms for predicting presynaptic and postsynaptic neurotoxins from sequence driven features by using Increment of Diversity (ID), Multinomial Naive Bayes Classifier (MNBC), Random Forest (RF), and K-nearest Neighbours Classifier (IBK). Each protein sequence was encoded by pseudo amino acid (PseAA) compositions and three biological motif features, including MEME, Prosite and InterPro motif features. The Maximum Relevance Minimum Redundancy (MRMR) feature selection method was used to rank the PseAA compositions and the 50 top ranked features were selected to improve the prediction accuracy. The PseAA compositions and three kinds of biological motif features were combined and 12 different parameters that defined as P1-P12 were selected as the input parameters of ID, MNBC, RF, and IBK. The prediction results obtained in this study were significantly better than those of previously developed methods.
Interferometric rotating point spread function
Authors: Wang Wei , Situ Guohai 
Published: July 2017

AbstractRotating point spread functions (PSF), such as the double helix (DH) PSF, are widely used in localization-based super-resolution imaging because of their large working depth range. In this article, we propose an interferometric DH PSF (iDH PSF) using two opposed objective lenses as in the 4Pi microscope. In the proposed iDH PSF, the super-resolution in the axial PSF is transferred to the azimuthal rotation. Moreover, we design an iDH PSF whose imaging range reaches 3 μm, which is roughly 3 times as much as that which can be obtained by using other interferometric localization-based super-resolution imaging methods.
Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes
Authors: Stevens Natalie E. , Chapman Marianne J. , Fraser Cara K. , Kuchel Tim R. , Hayball John D. , Diener Kerrilyn R. 
Published: July 2017

AbstractSepsis remains a significant health burden and a major clinical need exists for therapeutics to dampen the excessive and uncontrolled immune activation. Nuclear protein high mobility group box protein 1 (HMGB1) is released following cell death and is a late mediator in sepsis pathogenesis. While approaches targeting HMGB1 have demonstrated reduced mortality in pre-clinical models of sepsis, the impact of HMGB1 blockade on the complex septic inflammatory milieu and the development of subsequent immunosuppression remain enigmatic. Analysis of plasma samples obtained from septic shock patients established an association between increased HMGB1 and non-survival, higher APACHE II scores, and increased pro-inflammatory cytokine responses. Pre-clinically, administration of neutralising ovine anti-HMGB1 polyclonal antibodies improved survival in murine endotoxaemia and caecal ligation and puncture-induced sepsis models, and altered early cytokine profiles to one which corresponded to patterns observed in the surviving patient cohort. Additionally, anti-HMGB1 treated murine sepsis survivors were significantly more resistant to secondary bacterial infection and exhibited altered innate immune cell phenotypes and cytokine responses. These findings demonstrate that anti-HMGB1 antibodies alter inflammation in murine sepsis models and reduce sepsis mortality without potentiating immunosuppression.