bluuebunny/crossref_metadata_2025 huggingface dataset:
Deconvolution of DNA methylation identifies differentially methylated gene regions on 1p36 across breast cancer subtypes
Authors: Titus Alexander J. , Way Gregory P. , Johnson Kevin C. , Christensen Brock C.
Published: September 2017

Breast cancer is a complex disease consisting of four distinct molecular subtypes. DNA methylation-based (DNAm) studies in tumors are complicated further by disease heterogeneity. In the present study, we compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution to control for cellular heterogeneity. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P). These regions were consistently differentially methylated in every subtype and all implicated genes are localized to the chromosomal cytoband 1p36.3. Seventeen of these DMGRs were independently validated in a similar analysis of an external data set. The identification and validation of shared DNAm alterations across tumor subtypes in early stage tumors advances our understanding of common biology underlying breast carcinogenesis and may contribute to biomarker development. We also discuss evidence of the specific importance and potential function of 1p36 in cancer.
Global organization of a binding site network gives insight into evolution and structure-function relationships of proteins
Authors: Lee Juyong , Konc Janez , Janežič Dušanka , Brooks Bernard R.
Published: September 2017

The global organization of protein binding sites is analyzed by constructing a weighted network of binding sites based on their structural similarities and detecting communities of structurally similar binding sites based on the minimum description length principle. The analysis reveals that there are two central binding site communities that play the roles of the network hubs of smaller peripheral communities. The sizes of communities follow a power-law distribution, which indicates that the binding sites included in larger communities may be older and have been evolutionary structural scaffolds of more recent ones. Structurally similar binding sites in the same community bind to diverse ligands promiscuously and they are also embedded in diverse domain structures. Understanding the general principles of binding site interplay will pave the way for improved drug design and protein design.
Whole body and hematopoietic ADAM8 deficiency does not influence advanced atherosclerotic lesion development, despite its association with human plaque progression
Authors: Theodorou Kosta , van der Vorst Emiel P. C. , Gijbels Marion J. , Wolfs Ine M. J. , Jeurissen Mike , Theelen Thomas L. , Sluimer Judith C. , Wijnands Erwin , Cleutjens Jack P. , Li Yu , Jansen Yvonne , Weber Christian , Ludwig Andreas , Bentzon Jacob F. , Bartsch Jörg W. , Biessen Erik A. L. , Donners Marjo M. P. C.
Published: September 2017

Although A Disintegrin And Metalloproteinase 8 (ADAM8) is not crucial for tissue development and homeostasis, it has been implicated in various inflammatory diseases by regulating processes like immune cell recruitment and activation. ADAM8 expression has been associated with human atherosclerosis development and myocardial infarction, however a causal role of ADAM8 in atherosclerosis has not been investigated thus far. In this study, we examined the expression of ADAM8 in early and progressed human atherosclerotic lesions, in which ADAM8 was significantly upregulated in vulnerable lesions. In addition, ADAM8 expression was most prominent in the shoulder region of human atherosclerotic lesions, characterized by the abundance of foam cells. In mice, Adam8 was highly expressed in circulating neutrophils and in macrophages. Moreover, ADAM8 deficient mouse macrophages displayed reduced secretion of inflammatory mediators. Remarkably, however, neither hematopoietic nor whole-body ADAM8 deficiency in mice affected atherosclerotic lesion size. Additionally, except for an increase in granulocyte content in plaques of ADAM8 deficient mice, lesion morphology was unaffected. Taken together, whole body and hematopoietic ADAM8 does not contribute to advanced atherosclerotic plaque development, at least in female mice, although its expression might still be valuable as a diagnostic/prognostic biomarker to distinguish between stable and unstable lesions.
Reproducible and scalable purification of extracellular vesicles using combined bind-elute and size exclusion chromatography
Authors: Corso Giulia , Mäger Imre , Lee Yi , Görgens André , Bultema Jarred , Giebel Bernd , Wood Matthew J. A. , Nordin Joel Z. , Andaloussi Samir EL
Published: September 2017

Extracellular vesicles (EVs) play a pivotal role in cell-to-cell communication and have been shown to take part in several physiological and pathological processes. EVs have traditionally been purified by ultracentrifugation (UC), however UC has limitations, including resulting in, operator-dependant yields, EV aggregation and altered EV morphology, and moreover is time consuming. Here we show that commercially available bind-elute size exclusion chromatography (BE-SEC) columns purify EVs with high yield (recovery ~ 80%) in a time-efficient manner compared to current methodologies. This technique is reproducible and scalable, and surface marker analysis by bead-based flow cytometry revealed highly similar expression signatures compared with UC-purified samples. Furthermore, uptake of eGFP labelled EVs in recipient cells was comparable between BE-SEC and UC samples. Hence, the BE-SEC based EV purification method represents an important methodological advance likely to facilitate robust and reproducible studies of EV biology and therapeutic application.
Aspirin inhibits LPS-induced macrophage activation via the NF-κB pathway
Authors: Liu Yitong , Fang Silian , Li Xiaoyan , Feng Jie , Du Juan , Guo Lijia , Su Yingying , Zhou Jian , Ding Gang , Bai Yuxing , Wang Songling , Wang Hao , Liu Yi
Published: September 2017

Aspirin (acetylsalicylic acid, ASA) has been shown to improve bone marrow mesenchymal stem cell-based calvarial bone regeneration by promoting osteogenesis and inhibiting osteoclastogenesis. However, it remains unknown whether aspirin influences other immune cells during bone formation. In the present study, we investigated whether ASA treatment influenced macrophage activation during the LPS inducement. We found that ASA could downregulate the expressions of iNOS and TNF-α both in mouse peritoneum macrophages and RAW264.7 cells induced by LPS via the IκK/IκB/NF-κB pathway and a COX2/PGE2/EP2/NF-κB feedback loop, without affecting the expressions of FIZZ/YM-1/ARG1 induced by IL-4. Furthermore, we created a rat mandibular bone defect model and showed that ASA treatment improved bone regeneration by inhibiting LPS-induced macrophage activation in the early stages of inflammation. Taken together, our results indicated that ASA treatment was a feasible strategy for improving bone regeneration, particularly in inflammatory conditions.
Electric field and aging effects of uniaxial ferroelectrics Sr x Ba1−x Nb2O6 probed by Brillouin scattering
Authors: Aftabuzzaman M. , Helal M. A. , Paszkowski R. , Dec J. , Kleemann W. , Kojima S.
Published: September 2017

Static and dynamic heterogeneity of disordered system is one of the current topics in materials science. In disordered ferroelectric materials with random fields, dynamic polar nanoregions (PNRs) appear at Burns temperature and freeze into nanodomain state below Curie temperature (TC). This state is very sensitive to external electric field and aging by which it gradually switches into macrodomain state. However, the role of PNRs in such states belowTCis still a puzzling issue of materials science. Electric field and aging effects of uniaxial ferroelectric SrxBa1−xNb2O6(x = 0.40, SBN40) single crystals were studied using Brillouin scattering to clarify the critical nature of PNRs in domain states belowTC. On field heating, a broad anomaly in longitudinal acoustic (LA) velocity at low temperature region was due to an incomplete alignment of nanodomains caused by the interaction between PNRs. A sharp anomaly nearTCwas attributed to the complete switching of nanodomain to macrodomain state owing to the lack of interaction among PNRs. After isothermal aging belowTC, the noticeable increase of LA velocity was observed. It was unaffected by cyclic temperature measurements up toTC, and recovered to initial state outside of a narrow temperature range above and below aging temperature.
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

The 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

Genome-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

Our 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

SmartFlare 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

Colorectal 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

Children 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

Thermal 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

Metabolic 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

Vitamin 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

The 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

The 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

Comprehensive 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

Imaging 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

The 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

A 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

Indiscriminate 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.
Emergent spectral properties of river network topology: an optimal channel network approach
Authors: Abed-Elmdoust Armaghan , Singh Arvind , Yang Zong-Liang
Published: September 2017

Characterization of river drainage networks has been a subject of research for many years. However, most previous studies have been limited to quantities which are loosely connected to the topological properties of these networks. In this work, through a graph-theoretic formulation of drainage river networks, we investigate the eigenvalue spectra of their adjacency matrix. First, we introduce a graph theory model for river networks and explore the properties of the network through its adjacency matrix. Next, we show that the eigenvalue spectra of such complex networks follow distinct patterns and exhibit striking features including a spectral gap in which no eigenvalue exists as well as a finite number of zero eigenvalues. We show that such spectral features are closely related to the branching topology of the associated river networks. In this regard, we find an empirical relation for the spectral gap and nullity in terms of the energy dissipation exponent of the drainage networks. In addition, the eigenvalue distribution is found to follow a finite-width probability density function with certain skewness which is related to the drainage pattern. Our results are based on optimal channel network simulations and validated through examples obtained from physical experiments on landscape evolution. These results suggest the potential of the spectral graph techniques in characterizing and modeling river networks.
Microbial diversity in the hypersaline Lake Meyghan, Iran
Authors: Naghoni Ali , Emtiazi Giti , Amoozegar Mohammad Ali , Cretoiu Mariana Silvia , Stal Lucas J. , Etemadifar Zahra , Shahzadeh Fazeli Seyed Abolhassan , Bolhuis Henk
Published: September 2017

Lake Meyghan is one of the largest and commercially most important salt lakes in Iran. Despite its inland location and high altitude, Lake Meyghan has a thalassohaline salt composition suggesting a marine origin. Inputs of fresh water by rivers and rainfall formed various basins characterized by different salinities. We analyzed the microbial community composition of three basins by isolation and culturing of microorganisms and by analysis of the metagenome. The basins that were investigated comprised a green ~50 g kg−1 salinity brine, a red ~180 g kg−1 salinity brine and a white ~300 g kg−1 salinity brine. Using different growth media, 57 strains of Bacteria and 48 strains of Archaea were isolated. Two bacterial isolates represent potential novel species with less than 96% 16S rRNA gene sequence identity to known species. Abundant isolates were also well represented in the metagenome. Bacteria dominated the low salinity brine, with Alteromonadales (Gammaproteobacteria) as a particularly important taxon, whereas the high salinity brines were dominated by haloarchaea. Although the brines of Lake Meyghan differ in geochemical composition, their ecosystem function appears largely conserved amongst each other while being driven by different microbial communities.
Enhanced paramagnetism of mesoscopic graphdiyne by doping with nitrogen
Authors: Zhang Mingjia , Wang Xiaoxiong , Sun Huijuan , Wang Ning , Lv Qing , Cui Weiwei , Long Yunze , Huang Changshui
Published: September 2017

The new two-dimensional graphitic material, graphdiyne, has attracted great interest recently due to the superior intrinsic semiconductor properties. Here we investigate the magnetism of pure graphdiyne material and find it demonstrating a remarkable paramagnetic characteristic, which can be attributed to the appearance of special sp-hybridized carbon atoms. On this basis, we further introduce nitrogen with 5.29% N/C ratio into graphdiyne followed by simply annealing in a dopant source and realize a twofold enhancement of saturation moment at 2 K. Associate with the density of states calculation, we investigate the influence of the nitrogen atom doping sites on paramagnetism, and further reveal the important role of doped nitrogen atom on benzene ring in improving local magnetic moment. These results can not only help us deeply understand the intrinsic magnetism of graphdiyne, but also open an efficient way to improve magnetism of graphdiyne by hetero atom doping, like nitrogen doping, which may promote the potential application of graphdiyne in spintronics.
DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma
Authors: Ferraresso Serena , Aricò Arianna , Sanavia Tiziana , Da Ros Silvia , Milan Massimo , Cascione Luciano , Comazzi Stefano , Martini Valeria , Giantin Mery , Di Camillo Barbara , Mazzariol Sandro , Giannuzzi Diana , Marconato Laura , Aresu Luca
Published: September 2017

Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5′-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern. Functional analysis highlighted biological processes strongly related to embryonic development, tissue morphogenesis and cellular differentiation, including HOX, BMP and WNT. In addition, the analysis of epigenetic patterns and genome-wide methylation variability identified cDLBCL subgroups. Some of these epigenetic subtypes showed a concordance with the clinical outcome supporting the hypothesis that the accumulation of aberrant epigenetic changes results in a more aggressive behavior of the tumor. Collectively, our results suggest an important role of DNA methylation in DLBCL where aberrancies in transcription factors were frequently observed, suggesting an involvement during tumorigenesis. These findings warrant further investigation to improve cDLBCL prognostic classification and provide new insights on tumor aggressiveness.
Toll-like receptor 2 induced cytotoxic T-lymphocyte-associated protein 4 regulates Aspergillus-induced regulatory T-cells with pro-inflammatory characteristics
Authors: Raijmakers Ruud P. H. , Sprenkeler Evelien G. G. , Aleva Floor E. , Jacobs Cor W. M. , Kanneganti Thirumala-Devi , Joosten Leo A. B. , van de Veerdonk Frank L. , Gresnigt Mark S.
Published: September 2017

Patients with cystic fibrosis, chronic obstructive pulmonary disease, severe asthma, pre-existing pulmonary lesions, and severely immunocompromised patients are susceptible to develop infections with the opportunistic pathogenic fungus Aspergillus fumigatus, called aspergillosis. Infections in these patients are associated with persistent pro-inflammatory T-helper (TH)2 and TH17 responses. Regulatory T-cells, natural suppressor cells of the immune system, control pro-inflammatory T-cell responses, but can also contribute to disease by shifting to a pro-inflammatory TH17-like phenotype. Such a shift could play an important role in the detrimental immunopathology that is seen in aspergillosis. Our study demonstrates that Aspergillus fumigatus induces regulatory T-cells with a TH17-like phenotype. We also demonstrate that these regulatory T-cells with a pro-inflammatory TH17-like phenotype can be reprogrammed to their “classical” anti-inflammatory phenotype by activating Toll-like receptor 2 (TLR2), which regulates the induction of cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Similarly, soluble CTLA4 could reverse the pro-inflammatory phenotype of Aspergillus-induced regulatory T-cells. In conclusion, our results suggest a role for regulatory T-cells with a pro-inflammatory TH17-like phenotype in Aspergillus-associated immunopathology, and identifies key players, i.e. TLR2 and CTLA4, involved in this mechanism.
CScape: a tool for predicting oncogenic single-point mutations in the cancer genome
Authors: Rogers Mark F. , Shihab Hashem A. , Gaunt Tom R. , Campbell Colin
Published: September 2017

For somatic point mutations in coding and non-coding regions of the genome, we proposeCScape, an integrative classifier for predicting the likelihood that mutations are cancer drivers. Tested on somatic mutations,CScapetends to outperform alternative methods, reaching 91% balanced accuracy in coding regions and 70% in non-coding regions, while even higher accuracy may be achieved using thresholds to isolate high-confidence predictions. Positive predictions tend to cluster in genomic regions, so we apply a statistical approach to isolate coding and non-coding regions of the cancer genome that appear enriched for high-confidence predicted disease-drivers. Predictions and software are available athttp://CScape.biocompute.org.uk/.
Interference-exact radiative transfer equation
Authors: Partanen Mikko , Häyrynen Teppo , Oksanen Jani
Published: September 2017

The Purcell effect, i.e., the modification of the spontaneous emission rate by optical interference, profoundly affects the light-matter coupling in optical resonators. Fully describing the optical absorption, emission, and interference of light hence conventionally requires combining the full Maxwell’s equations with stochastic or quantum optical source terms accounting for the quantum nature of light. We show that both the nonlocal wave and local particle features associated with interference and emission of propagating fields in stratified geometries can be fully captured by local damping and scattering coefficients derived from the recently introduced quantized fluctuational electrodynamics (QFED) framework. In addition to describing the nonlocal optical interference processes as local directionally resolved effects, this allows reformulating the well known and widely used radiative transfer equation (RTE) as a physically transparent interference-exact model that extends the useful range of computationally efficient and quantum optically accurate interference-aware optical models from simple structures to full optical devices.
Impacts of light limitation on corals and crustose coralline algae
Authors: Bessell-Browne Pia , Negri Andrew P. , Fisher Rebecca , Clode Peta L. , Jones Ross
Published: September 2017

Turbidity associated with elevated suspended sediment concentrations can significantly reduce underwater light availability. Understanding the consequences for sensitive organisms such as corals and crustose coralline algae (CCA), requires an understanding of tolerance levels and the time course of effects. Adult colonies of Acropora millepora and Pocillopora acuta, juvenile P. acuta, and the CCA Porolithon onkodes were exposed to six light treatments of ~0, 0.02, 0.1, 0.4, 1.1 and 4.3 mol photons m−2 d−1, and their physiological responses were monitored over 30 d. Exposure to very low light (<0.1 mol photons m-2 d-1) caused tissue discoloration (bleaching) in the corals, and discolouration (and partial mortality) of the CCA, yielding 30 d EI10 thresholds (irradiance which results in a 10% change in colour) of 1.2–1.9 mol photons m−2 d−1. Recent monitoring studies during dredging campaigns on a shallow tropical reef, have shown that underwater light levels very close (~500 m away) from a working dredge routinely fall below this value over 30 d periods, but rarely during the pre-dredging baseline phase. Light reduction alone, therefore, constitutes a clear risk to coral reefs from dredging, although at such close proximity other cause-effect pathways, such as sediment deposition and smothering, are likely to also co-occur.
Mitigating Motor Neuronal Loss in C. elegans Model of ALS8
Authors: Zhang Wendy , Colavita Antonio , Ngsee Johnny K.
Published: September 2017

ALS8 is a late-onset familial autosomal dominant form of Amyotrophic Lateral Sclerosis (ALS) caused by a point mutation (P56S) in the VAPB gene (VAMP associated protein isoform B). Here, we generated two C. elegans models of the disease: a transgenic model where human VAPB wild-type (WT) or P56S mutant was expressed in a subset of motor neurons, and a second model that targeted inducible knockdown of the worm’s orthologue, vpr-1. Overexpression of human VAPB in DA neurons caused a backward locomotion defect, axonal misguidance, and premature neuronal death. Knockdown of vpr-1 recapitulated the reduction in VAPB expression associated with sporadic cases of human ALS. It also caused backward locomotion defects as well as an uncoordinated phenotype, and age-dependent, progressive motor neuronal death. Furthermore, inhibiting phosphatidylinositol-4 (PtdIns 4)-kinase activity with PIK-93 reduced the incidence of DA motor neuron loss and improved backward locomotion. This supports the loss of VAPB function in ALS8 pathogenesis and suggests that reducing intracellular PtdIns4P might be an effective therapeutic strategy in delaying progressive loss of motor neurons.
Antimutagenic and antioxidant activity of the essential oils of Citrus sinensis and Citrus latifolia
Authors: Toscano-Garibay J. D. , Arriaga-Alba M. , Sánchez-Navarrete J. , Mendoza-García M. , Flores-Estrada J. J. , Moreno-Eutimio M. A. , Espinosa-Aguirre J. J. , González-Ávila M. , Ruiz-Pérez N. J.
Published: September 2017

The essential oils of Citrus sinensis and Citrus latifolia showed antimycotic activity against Candida spp. isolated from the oral cavity; they are neither mutagenic on the Ames test nor cytotoxic. Their main components are R-(+)-limonene, β-thujene, α-myrcene and γ-terpinene. The aim of this work was to evaluate their antimutagenic and antioxidant capacities. Antimutagenic properties were evaluated against MNNG and ENNG on S. typhimurium TA100; against 2AA on strain TA98 and in front of 4NQO and NOR on strain TA102. Both were antimutagenic against MNNG (p < 0.001) but only C. latifolia was antimutagenic against ENNG (p < 0.001). Both presented antimutagenic activity against 2AA (p < 0.001). They were antioxidant against the ROS-generating compound 4NQO (p < 0.001) and the antibiotic NOR (p < 0.001). In the antioxidant evaluation, the activity in DPPH assay was in a range of 6–23% for C. sinensis and of 22–71% for C. latifolia. Both were antioxidant compared with BHT in β-carotene bleaching assay and were able to decreased apoptosis in HaCat cells stimulated with H2O2. The levels of intracellular superoxide ion were lower in the presence of both oils. In conclusion, the essential oils of C. sinensis and C. latifolia are antimutagenic against at least three types of mutagens and have antioxidants properties.
Polarization-independent, wide-incident-angle and dual-band perfect absorption, based on near-field coupling in a symmetric metamaterial
Authors: Tung Bui Son , Khuyen Bui Xuan , Kim Young Ju , Lam Vu Dinh , Kim Ki Won , Lee YoungPak
Published: September 2017

We numerically and experimentally investigated a dual-band metamaterial perfect absorber (MPA), utilizing the near-field coupling of double split-ring resonators (DSRRs). Owing to the near-field coupling between resonators, two arms in each DSRR resonate in different phases, leading to a dual-band perfect absorption. The proposed MPA also exhibits polarization-insensitive behavior and maintains the high absorption above 90% up to a wide range of incident angle more than 45°. Finally, to further consolidate our approach, a multi-band absorption is also studied by exploiting the near-field coupling among a larger number of DSRRs. Our work is expected to be applied to future broadband devices using MPA.