bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mechano-sensing role of the unique SH3 insertion in plakin domains revealed by Molecular Dynamics simulations
Authors: Daday Csaba , Kolšek Katra , Gräter Frauke 
Published: September 2017

AbstractThe plakin family of proteins, important actors in cross-linking force-bearing structures in the cell, contain a curious SH3 domain insertion in their chain of spectrin repeats (SRs). While SH3 domains are known to mediate protein-protein interactions, here, its canonical binding site is autoinhibited by the preceding SR. Under force, however, this SH3 domain could be released, and possibly launch a signaling cascade. We performed large-scale force-probe molecular dynamics simulations, across two orders of magnitude of loading rates, to test this hypothesis, on two prominent members of the plakin family: desmoplakin and plectin, obligate proteins at desmosomes and hemidesmosomes, respectively. Our simulations show that force unravels the SRs and abolishes the autoinhibition of the SH3 domain, an event well separated from the unfolding of this domain. The SH3 domain is free and fully functional for a significant portion of the unfolding trajectories. The rupture forces required for the two proteins significantly decrease when the SH3 domain is removed, which implies that the SH3 domain also stabilizes this junction. Our results persist across all simulations, and support a force-sensing as well as a stabilizing role of the unique SH3 insertion, putting forward this protein family as a new class of mechano-sensors.
Niche harmony search algorithm for detecting complex disease associated high-order SNP combinations
Authors: Tuo Shouheng , Zhang Junying , Yuan Xiguo , He Zongzhen , Liu Yajun , Liu Zhaowen 
Published: September 2017

AbstractGenome-wide association study is especially challenging in detecting high-order disease-causing models due to model diversity, possible low or even no marginal effect of the model, and extraordinary search and computations. In this paper, we propose a niche harmony search algorithm where joint entropy is utilized as a heuristic factor to guide the search for low or no marginal effect model, and two computationally lightweight scores are selected to evaluate and adapt to diverse of disease models. In order to obtain all possible suspected pathogenic models, niche technique merges with HS, which serves as a taboo region to avoid HS trapping into local search. From the resultant set of candidate SNP-combinations, we use G-test statistic for testing true positives. Experiments were performed on twenty typical simulation datasets in which 12 models are with marginal effect and eight ones are with no marginal effect. Our results indicate that the proposed algorithm has very high detection power for searching suspected disease models in the first stage and it is superior to some typical existing approaches in both detection power and CPU runtime for all these datasets. Application to age-related macular degeneration (AMD) demonstrates our method is promising in detecting high-order disease-causing models.
Molecular mechanisms underlying the involvement of the sigma-1 receptor in methamphetamine-mediated microglial polarization
Authors: Chao Jie , Zhang Yuan , Du Longfei , Zhou Rongbin , Wu Xiaodong , Shen Kai , Yao Honghong 
Published: September 2017

AbstractOur previous study demonstrated that the sigma-1 receptor is involved in methamphetamine-induced microglial apoptosis and death; however, whether the sigma-1 receptor is involved in microglial activation as well as the molecular mechanisms underlying this process remains poorly understood. The aim of this study is to demonstrate the involvement of the sigma-1 receptor in methamphetamine-mediated microglial activation. The expression of σ-1R, iNOS, arginase and SOCS was examined by Western blot; activation of cell signaling pathways was detected by Western blot analysis. The role of σ-1R in microglial activation was further validated in C57BL/6 N WT and sigma-1 receptor knockout mice (male, 6–8 weeks) injected intraperitoneally with saline or methamphetamine (30 mg/kg) by Western blot combined with immunostaining specific for Iba-1. Treatment of cells with methamphetamine (150 μM) induced the expression of M1 markers (iNOS) with concomitant decreased the expression of M2 markers (Arginase) via its cognate sigma-1 receptor followed by ROS generation. Sequential activation of the downstream MAPK, Akt and STAT3 pathways resulted in microglial polarization. Blockade of sigma-1 receptor significantly inhibited the generation of ROS and activation of the MAPK and Akt pathways. These findings underscore the critical role of the sigma-1 receptor in methamphetamine-induced microglial activation.
SmartFlares fail to reflect their target transcripts levels
Authors: Czarnek Maria , Bereta Joanna 
Published: September 2017

AbstractSmartFlare probes have recently emerged as a promising tool for visualisation and quantification of specific RNAs in living cells. They are supposed to overcome the common drawbacks of current methods for RNA analysis: the need of cell fixation or lysis, or the requirements for genetic manipulations. In contrast to the traditional methods, SmartFlare probes are also presumed to provide information on RNA levels in single cells. Disappointingly, the results of our comprehensive study involving probes specific to five different transcripts, HMOX1, IL6, PTGS2, Nrg1, and ERBB4, deny the usefulness of SmartFlare probes for RNA analysis. We report a total lack of correlation between fluorescence intensities of SmartFlare probes and the levels of corresponding RNAs assessed by RT-qPCR. To ensure strong differences in the levels of analysed RNAs, their expression was modified via: (i) HMOX1-knockdown generated by CRISPR-Cas9 genome editing, (ii) hemin-mediated stimulation of HMOX1- and IL1β-mediated stimulation of IL6- and PTGS2 transcription, (iii) lentiviral vector-mediated Nrg1 overexpression. Additionally, ERBB4-specific SmartFlare probe failed to distinguish between ERBB4-expressing and non-expressing cell lines. Finally, we demonstrated that fluorescence intensity of HMOX1-specific SmartFlare probe corresponds to the efficacy of its uptake and/or accumulation.
Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer
Authors: Purcell Rachel V. , Visnovska Martina , Biggs Patrick J. , Schmeier Sebastian , Frizelle Frank A. 
Published: September 2017

AbstractColorectal cancer (CRC) is a heterogeneous disease and recent advances in subtype classification have successfully stratified the disease using molecular profiling. The contribution of bacterial species to CRC development is increasingly acknowledged, and here, we sought to analyse CRC microbiomes and relate them to tumour consensus molecular subtypes (CMS), in order to better understand the relationship between bacterial species and the molecular mechanisms associated with CRC subtypes. We classified 34 tumours into CRC subtypes using RNA-sequencing derived gene expression and determined relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding. 16S rRNA analysis showed enrichment of Fusobacteria and Bacteroidetes, and decreased levels of Firmicutes and Proteobacteria in CMS1. A more detailed analysis of bacterial taxa using non-human RNA-sequencing reads uncovered distinct bacterial communities associated with each molecular subtype. The most highly enriched species associated with CMS1 included Fusobacterium hwasookii and Porphyromonas gingivalis. CMS2 was enriched for Selenomas and Prevotella species, while CMS3 had few significant associations. Targeted quantitative PCR validated these findings and also showed an enrichment of Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus stomatis in CMS1. In this study, we have successfully associated individual bacterial species to CRC subtypes for the first time.
Children and adults with Attention-Deficit/Hyperactivity Disorder cannot move to the beat
Authors: Puyjarinet Frédéric , Bégel Valentin , Lopez Régis , Dellacherie Delphine , Dalla Bella Simone 
Published: September 2017

AbstractChildren and adults with Attention-Deficit Hyperactivity Disorder (ADHD) fail in simple tasks like telling whether two sounds have different durations, or in reproducing single durations. The deficit is linked to poor reading, attention, and language skills. Here we demonstrate that these timing distortions emerge also when tracking the beat of rhythmic sounds in perceptual and sensorimotor tasks. This contrasts with the common observation that durations are better perceived and produced when embedded in rhythmic stimuli. Children and adults with ADHD struggled when moving to the beat of rhythmic sounds, and when detecting deviations from the beat. Our findings point to failure in generating an internal beat in ADHD while listening to rhythmic sounds, a function typically associated with the basal ganglia. Rhythm-based interventions aimed at reinstating or compensating this malfunctioning circuitry may be particularly valuable in ADHD, as already shown for other neurodevelopmental disorders, such as dyslexia and Specific Language Impairment.
Thermal properties of Zn2(C8H4O4)2•C6H12N2 metal-organic framework compound and mirror symmetry violation of dabco molecules
Authors: Kozlova Svetlana G. , Gabuda Svyatoslav P. 
Published: September 2017

AbstractThermal properties of Zn2(C8H4O4)2•C6H12N2 metal-organic framework compound at 8–300 K suggest the possibility of subbarrier tunnelling transitions between left-twisted (S) and right-twisted (R) forms of C6H12N2 dabco molecules with D3 point symmetry. The data agree with those obtained for the temperature behavior of nuclear spin-lattice relaxation times. It is shown that there is a temperature range where the transitions are stopped. Therefore, Zn2(C8H4O4)2•C6H12N2 and related compounds are interesting objects to study the effect of spontaneous mirror-symmetry breaking and stabilization of chiral isomeric molecules in solids at low temperatures.
Association between HOMA-IR and Lung Function in Korean Young Adults based on the Korea National Health and Nutrition Examination Survey
Authors: Lee Young Bok , Kim Young Soo , Lee Dong-Hee , Kim Hee Yeon , Lee Jae-Im , Ahn Hyo-Suk , Sohn Tae Seo , Lee Tae-Kyu , Song Jae Yen , Yeo Chang Dong , Hong Mihee , Han Kyungdo , Jeong Seong Cheol , Chae Hiun Suk 
Published: September 2017

AbstractMetabolic syndrome, including obesity and insulin resistance, has been reported to lower lung function in elderly subjects with asthma or chronic obstructive lung disease. This study aimed to find the association between lung function and insulin resistance in Korean young adults. This study used data from the Korean National Health and Nutrition Examination Survey 2011–2013, which is a representative sample of the Korean population. A total of 1,922 young adults aged 19 to 40 were included in the analysis. The association between lung function test and insulin resistance was evaluated. Weighted logistic regression analyses showed a significant negative correlation of insulin resistance with FVC% predicted (correlation coefficient γ = −0.130, P < 0.0001), FEV1% predicted (γ = −0.074, P = 0.004) and FEV1/FVC ratio (γ = −0.059, P = 0.019) in young adults, especially in subjects without asthma (γ for FVC% predicted, FEV1% predicted and FEV1/FVC ratio = −0.138, −0.092, and −0.061, respectively). This study demonstrates an inverse correlation between insulin resistance and lung function in Korean young adults. Young adults with preclinical insulin resistance have a higher risk of impaired lung function.
Ultraviolet B Light Emitting Diodes (LEDs) Are More Efficient and Effective in Producing Vitamin D3 in Human Skin Compared to Natural Sunlight
Authors: Kalajian T. A. , Aldoukhi A. , Veronikis A. J. , Persons K. , Holick M. F. 
Published: September 2017

AbstractVitamin D, the sunshine vitamin is important for health. Those with fat malabsorption disorders malabsorb vitamin D and thus must rely on cutaneous production of vitamin D3. Vitamin D3 is generated secondary to exposure to ultraviolet B (UVB) radiation (whether from the sun or from an artificial source). Light emitting diodes (LEDs) have been developed to emit ultraviolet radiation. Little is known about the efficiency of UVB emitting LEDs tuned to different wavelengths for producing vitamin D3 in human skin. Ampoules containing 7-dehydrocholesterol were exposed to a LED that emitted a peak wavelength at 293, 295, 298 or 305 nm to determine their efficiency to produce previtamin D3. The 293 nm LED was best suited for evaluating its effectiveness for producing vitamin D in human skin due to the shorter exposure time. This LED was found to be 2.4 times more efficient in producing vitamin D3 in human skin than the sun in less than 1/60th the time. This has significant health implications for medical device development in the future that can be used for providing vitamin D supplementation to patients with fat malabsorption syndromes as well as patients with other metabolic abnormalities including patients with chronic kidney disease.
Genome-wide RAD sequencing data provide unprecedented resolution of the phylogeny of temperate bamboos (Poaceae: Bambusoideae)
Authors: Wang Xueqin , Ye Xiaying , Zhao Lei , Li Dezhu , Guo Zhenhua , Zhuang Huifu 
Published: September 2017

AbstractThe temperate bamboos (tribe Arundinarieae, Poaceae) are strongly supported as monophyly in recent molecular studies, but taxonomic delineation and phylogenetic relationships within the tribe lack resolution. Here, we sampled 39 species (36 temperate bamboos and 3 outgroups) for restriction-site associated DNA sequencing (RAD-seq) with an emphasis onPhyllostachysclade and related clades. Using the largest data matrix for the bamboos to date, we were able to infer phylogenetic relationships with unparalleled resolution. ThePhyllostachys,Shibataea, andArundinariaclades defined from plastid phylogeny, were not supported as monophyletic group. However, the RAD-seq phylogeny largely agreed with the morphology-based taxonomy, with two clades having leptomorph rhizomes strongly supported as monophyletic group. We also explored two approaches, BWA-GATK (a mapping system) and Stacks (a grouping system), for differences in SNP calling and phylogeny inference. For the same level of missing data, the BWA-GATK pipeline produced much more SNPs in comparison with Stacks. Phylogenetic analyses of the largest data matrices from both pipelines, using concatenation and coalescent methods provided similar tree topologies, despite the presence of missing data. Our study demonstrates the utility of RAD-seq data for elucidating phylogenetic relationships between genera and higher taxonomic levels in this important but phylogenetically challenging group.
Endogenous ω-3 Fatty Acid Production by fat-1 Transgene and Topically Applied Docosahexaenoic Acid Protect against UVB-induced Mouse Skin Carcinogenesis
Authors: Yum Hye-Won , Park Jin , Park Hyun-Jung , Shin Jun Wan , Cho Yong-Yeon , Kim Su-Jung , Kang Jing X. , Surh Young-Joon 
Published: September 2017

AbstractThe present study was intended to explore the effects of endogenously produced ω-3 polyunsaturated fatty acids (PUFAs) on ultraviolet B (UVB)-induced skin inflammation and photocarcinogenesis using hairless fat-1 transgenic mice harboring ω-3 desaturase gene capable of converting ω-6 to ω-3 PUFAs. Upon exposure to UVB irradiation, fat-1 transgenic mice exhibited a significantly reduced epidermal hyperplasia, oxidative skin damage, and photocarcinogenesis as compared to wild type mice. The transcription factor, Nrf2 is a master regulator of anti-inflammatory and antioxidant gene expression. While the protein expression of Nrf2 was markedly enhanced, the level of its mRNA transcript was barely changed in the fat-1 transgenic mouse skin. Topical application of docosahexaenoic acid (DHA), a representative ω-3 PUFA, in wild type hairless mice induced expression of the Nrf2 target protein, heme oxygenase-1 in the skin and protected against UVB-induced oxidative stress, inflammation and papillomagenesis. Furthermore, transient overexpression of fat-1 gene in mouse epidermal JB6 cells resulted in the enhanced accumulation of Nrf2 protein. Likewise, DHA treated to JB6 cells inhibited Nrf2 ubiquitination and stabilized it. Taken together, our results indicate that functional fat-1 and topically applied DHA potentiate cellular defense against UVB-induced skin inflammation and photocarcinogenesis through elevated activation of Nrf2 and upregulation of cytoprotective gene expression.
Automated N-Glycosylation Sequencing Of Biopharmaceuticals By Capillary Electrophoresis
Authors: Szigeti Marton , Guttman Andras 
Published: September 2017

AbstractComprehensive analysis of the N-linked carbohydrates of glycoproteins is gaining high recent interest in both the biopharmaceutical and biomedical fields. In addition to high resolution glycosylation profiling, sugar residue and linkage specific enzymes are also routinely used for exoglycosidase digestion based carbohydrate sequencing. This latter one, albeit introduced decades ago, still mostly practiced by following tedious and time consuming manual processes. In this paper we introduce an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. The enzymatic reactions were accomplished within the temperature controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. CE analysis was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods, respectively.
Real-time Image Processing for Microscopy-based Label-free Imaging Flow Cytometry in a Microfluidic Chip
Authors: Heo Young Jin , Lee Donghyeon , Kang Junsu , Lee Keondo , Chung Wan Kyun 
Published: September 2017

AbstractImaging flow cytometry (IFC) is an emerging technology that acquires single-cell images at high-throughput for analysis of a cell population. Rich information that comes from high sensitivity and spatial resolution of a single-cell microscopic image is beneficial for single-cell analysis in various biological applications. In this paper, we present a fast image-processing pipeline (R-MOD: Real-time Moving Object Detector) based on deep learning for high-throughput microscopy-based label-free IFC in a microfluidic chip. The R-MOD pipeline acquires all single-cell images of cells in flow, and identifies the acquired images as a real-time process with minimum hardware that consists of a microscope and a high-speed camera. Experiments show that R-MOD has the fast and reliable accuracy (500 fps and 93.3% mAP), and is expected to be used as a powerful tool for biomedical and clinical applications.
Structured illumination microscopy and automatized image processing as a rapid diagnostic tool for podocyte effacement
Authors: Siegerist Florian , Ribback Silvia , Dombrowski Frank , Amann Kerstin , Zimmermann Uwe , Endlich Karlhans , Endlich Nicole 
Published: September 2017

AbstractThe morphology of podocyte foot processes is obligatory for renal function. Here we describe a method for the superresolution-visualization of podocyte foot processes using structured illumination microscopy of the slit diaphragm, which before has only been achieved by electron microscopy. As a proof of principle, we measured a mean foot process width of 0.249 ± 0.068 µm in healthy kidneys and a significant higher mean foot process width of 0.675 ± 0.256 µm in minimal change disease patients indicating effacement of foot processes. We then hypothesized that the slit length per glomerular capillary surface area (slit diaphragm density) could be used as an equivalent for the diagnosis of effacement. Using custom-made software we measured a mean value of 3.10 ± 0.27 µm−1 in healthy subjects and 1.83 ± 0.49 µm−1 in the minimal change disease patients. As foot process width was highly correlated with slit diaphragm density (R2 = 0.91), we concluded that our approach is a valid method for the diagnosis of foot process effacement. In summary, we present a new technique to quantify podocyte damage, which combines superresolution microscopy with automatized image processing. Due to its diverse advantages, we propose this technique to be included into routine diagnostics of glomerular histopathology.
Green Perovskite Distributed Feedback Lasers
Authors: Harwell J. R. , Whitworth G. L. , Turnbull G. A. , Samuel I. D. W. 
Published: September 2017

AbstractA visible perovskite distributed feedback laser is fabricated for the first time. Through the use of nanocrystal pinning, highly luminescent methylammonium lead bromide films are used to produce stable lasers emitting at 550 nm, with a low threshold of 6 µJcm−2. The lasers were able to support multiple polarisations, and could be switched between transverse magnetic and transverse electric mode operation through simple tuning of the distributed feedback grating period.
Diphenyleneiodonium chloride (DPIC) displays broad-spectrum bactericidal activity
Authors: Pandey Manitosh , Singh Alok Kumar , Thakare Ritesh , Talwar Sakshi , Karaulia Pratiksha , Dasgupta Arunava , Chopra Sidharth , Pandey Amit Kumar 
Published: September 2017

AbstractIndiscriminate use of antibiotics globally has lead to an increase in emergence of drug-resistant pathogens under both nosocomial, as well as more worryingly, in community setting as well. Further, a decrease in the corporate interest and financial commitment has exerted increasing pressure on a rapidly dwindling antimicrobial drug discovery and developmental program. In this context, we have screened the Library of Pharmacologically Active Compounds (LOPAC, Sigma) against Staphylococcus aureus and Mycobacterium tuberculosis to identify potent novel antimicrobial molecules amongst non-antibiotic molecules. Microplate-based whole cell growth assay was performed to analyze the antimicrobial potency of the compounds against Staphylococcus aureus and Mycobacterium tuberculosis. We identified diphenyleneiodonium chloride, a potent inhibitor of NADH/NADPH oxidase, as a broad-spectrum antibiotic potently active against drug resistant strains of Staphylococcus aureus and Mycobacterium tuberculosis. Intriguingly, the diphenyleneiodonium chloride was also very effective against slow-growing non-replicating Mtb persisters. FIC index demonstrated a strongly synergistic interaction between diphenyleneiodonium chloride and Rifampicin while it did not interact with INH. The antimicrobial property of the diphenyleneiodonium chloride was further validated in vivo murine neutropenic thigh S. aureus infection model. Taken together, these findings suggest that Diphenyleneiodonium chloride can be potentially repurposed for the treatment of tuberculosis and staphylococcal infections.