bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide Identification and Characterization of Natural Antisense Transcripts by Strand-specific RNA Sequencing in Ganoderma lucidum
Authors: Shao Junjie , Chen Haimei , Yang Dan , Jiang Mei , Zhang Hui , Wu Bin , Li Jianqin , Yuan Lichai , Liu Chang
Published: July 2017

Ganoderma lucidum is a white-rot fungus best-known for its medicinal and ligninolytic activities. To discover the underlying genes responsible for these activities, we identified and characterized the natural antisense transcripts (NATs) using strand-specific (ss) RNA-seq data obtained from the mycelia, primordia and fruiting bodies. NATs were identified using a custom pipeline and then subjected to functional enrichment and differential expression analyses. A total of 1613 cis- and 244 trans- sense and antisense transcripts were identified. Mapping to GO terms and KEGG pathways revealed that NATs were frequently associated with genes of particular functional categories in particular stages. ssRT-qPCR experiments showed that the expression profiles of 30 of 50 (60%) transcripts were highly correlated with those of the RNA-seq results (r ≥ 0.9). Expression profiles of 22 of 25 (88%) pairs of NATs and STs were highly correlated (p ≤ 0.01), with 15 having r ≥ 0.8 and 4 having r ≤ -0.8. Six lignin-modifying genes and their NATs were analyzed in detail. Diverse patterns of differential expression among different stages and positive and negative correlations were observed. These results suggested that NATs were implicated in gene expression regulation in a function-group and developmental-stage specific manner through complex mechanisms.
Multi-pinhole fluorescent x-ray computed tomography for molecular imaging
Authors: Sasaya Tenta , Sunaguchi Naoki , Hyodo Kazuyuki , Zeniya Tsutomu , Yuasa Tetsuya
Published: July 2017

We propose a multi-pinhole fluorescent x-ray computed tomography (mp-FXCT) technique for preclinical molecular imaging that can provide the complete data necessary to produce 3-D tomographic images during anaesthesia. In this method, multiple projections are simultaneously acquired through a multi-pinhole collimator with a 2-D detector and full-field volumetric beam to accelerate the data acquisition process and enhance the signal-to-noise ratios of the projections. We constructed a 15-pinhole mp-FXCT imaging system at beamline ARNE-7A at KEK and performed preliminary experiments to investigate its imaging properties using physical phantoms and a non-radioactive I imaging agent. The mp-FXCT system could detect an I concentration of 0.038 mg/ml, the minimum required for in-vivo imaging, at a spatial resolution of about 0.3 mm during a data acquisition time of 90 min, which is less than the time for which anaesthesia is effective and suggests that preclinical molecular imaging is feasible with mp-FXCT.
A novel fluorescent probe-based flow cytometric assay for mineral-containing nanoparticles in serum
Authors: Smith Edward R. , Hewitson Tim D. , Cai Michael M. X. , Aghagolzadeh Parisa , Bachtler Matthias , Pasch Andreas , Holt Stephen G.
Published: July 2017

Calciprotein particles, nanoscale aggregates of insoluble mineral and binding proteins, have emerged as potential mediators of phosphate toxicity in patients with Chronic Kidney Disease. Although existing immunochemical methods for their detection have provided compelling data, these approaches are indirect, lack specificity and are subject to a number of other technical and theoretical shortcomings. Here we have developed a rapid homogeneous fluorescent probe-based flow cytometric method for the detection and quantitation of individual mineral-containing nanoparticles in human and animal serum. This method allows the discrimination of membrane-bound from membrane-free particles and different mineral phases (amorphous vs. crystalline). Critically, the method has been optimised for use on a conventional instrument, without the need for manual hardware adjustments. Using this method, we demonstrate a consistency in findings across studies of Chronic Kidney Disease patients and commonly used uraemic animal models. These studies demonstrate that renal dysfunction is associated with the ripening of calciprotein particles to the crystalline state and reveal bone metabolism and dietary mineral as important modulators of circulating levels. Flow cytometric analysis of calciprotein particles may enhance our understanding of mineral handling in kidney disease and provide a novel indicator of therapeutic efficacy for interventions targeting Chronic Kidney Disease-Mineral Bone Disorder.
Calcifying algae maintain settlement cues to larval abalone following algal exposure to extreme ocean acidification
Authors: O’Leary Jennifer K. , Barry James P. , Gabrielson Paul W. , Rogers-Bennett Laura , Potts Donald C. , Palumbi Stephen R. , Micheli Fiorenza
Published: July 2017

Ocean acidification (OA) increasingly threatens marine systems, and is especially harmful to calcifying organisms. One important question is whether OA will alter species interactions. Crustose coralline algae (CCA) provide space and chemical cues for larval settlement. CCA have shown strongly negative responses to OA in previous studies, including disruption of settlement cues to corals. In California, CCA provide cues for seven species of harvested, threatened, and endangered abalone. We exposed four common CCA genera and a crustose calcifying red algae,Peyssonnelia(collectively CCRA) from California to three pCO2levels ranging from 419–2,013 µatm for four months. We then evaluated abalone (Haliotis rufescens) settlement under ambient conditions among the CCRA and non-algal controls that had been previously exposed to the pCO2treatments. Abalone settlement and metamorphosis increased from 11% in the absence of CCRA to 45–69% when CCRA were present, with minor variation among CCRA genera. Though all CCRA genera reduced growth during exposure to increased pCO2, abalone settlement was unaffected by prior CCRA exposure to increased pCO2. Thus, we find no impacts of OA exposure history on CCRA provision of settlement cues. Additionally, there appears to be functional redundancy in genera of CCRA providing cues to abalone, which may further buffer OA effects.
Quantitative Measurement of the Thyroid Uptake Function of Mouse by Cerenkov Luminescence Imaging
Authors: Ke Chien-Chih , He Zi-Ming , Hsieh Ya-Ju , Huang Chia-Wen , Li Jia-Je , Hwu Luen , Chen Yi-An , Yang Bang-Hung , Chang Chi-Wei , Huang Wen-Sheng , Liu Ren-Shyan
Published: July 2017

Cerenkov luminescence imaging (CLI) has been an evolutional and alternative approach of nuclear imaging in basic research. This study aimed to measure the 131I thyroid uptake of mouse using CLI for assessment of thyroid function. Quantification of 131I thyroid uptake of mice in euthyroid, hypothyroid and hyperthyroid status was performed by CLI and γ-scintigraphy at 24 hours after injection of 131I. The 131I thyroid uptake was calculated using the equation: (thyroid counts − background counts)/(counts of injected dose of 131I) × 100%. Serum T4 concentration was determined to evaluate the thyroid function. The radioactivity of 131I was linearly correlated with the CL signals in both in vitro and in vivo measurements. CLI showed a significant decrease and increase of 131I thyroid uptake in the mice in hypo- and hyperfunctioning status, respectively, and highly correlated with that measured by γ-scintigraphy. However, the percent thyroid uptake measured by CLI were one-fifth of those measured by γ-scintigraphy due to insufficient tissue penetration of CL. These results indicate that CLI, in addition to nuclear imaging, is able to image and evaluate the 131I thyroid uptake function in mice in preclinical and research settings.
Betulinic acid is a PPARγ antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis
Authors: Brusotti Gloria , Montanari Roberta , Capelli Davide , Cattaneo Giulia , Laghezza Antonio , Tortorella Paolo , Loiodice Fulvio , Peiretti Franck , Bonardo Bernadette , Paiardini Alessandro , Calleri Enrica , Pochetti Giorgio
Published: July 2017

PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, and they serve as an alternative treatment for metabolic diseases. In this work, an affinity-based bioassay was found to be effective for selecting PPAR ligands from the dried extract of an African plant (Diospyros bipindensis). Among the ligands, we identified betulinic acid (BA), a compound already known for its anti-inflammatory, anti-tumour and antidiabetic properties, as a PPARγ and PPARα antagonist. Cell differentiation assays showed that BA inhibits adipogenesis and promotes osteogenesis; either down-regulates or does not affect the expression of a series of adipogenic markers; and up-regulates the expression of osteogenic markers. Moreover, BA increases basal glucose uptake in 3T3-L1 adipocytes. The crystal structure of the complex of BA with PPARγ sheds light, at the molecular level, on the mechanism by which BA antagonizes PPARγ, and indicates a unique binding mode of this antagonist type. The results of this study show that the natural compound BA could be an interesting and safe candidate for the treatment of type 2 diabetes and bone diseases.
Comparison between an African town and a neighbouring village shows delayed, but not decreased, sleep during the early stages of urbanisation
Authors: Beale Andrew D. , Pedrazzoli Mario , Gonçalves Bruno da Silva B. , Beijamini Felipe , Duarte Núbia E. , Egan Kieren J. , Knutson Kristen L. , Schantz Malcolm von , Roden Laura C.
Published: July 2017

The well-established negative health outcomes of sleep deprivation, and the suggestion that availability of electricity may enable later bed times without compensating sleep extension in the morning, have stimulated interest in studying communities whose sleep pattern may resemble a pre-industrial state. Here, we describe sleep and activity in two neighbouring communities, one urban (Milange) and one rural (Tengua), in a region of Mozambique where urbanisation is an ongoing process. The two communities differ in the amount and timing of daily activity and of light exposure, with later bedtimes (≈1 h) associated with more evening and less daytime light exposure seen in the town of Milange. In contrast to previous reports comparing communities with and without electricity, sleep duration did not differ between Milange (7.28 h) and Tengua (7.23 h). Notably, calculated sleep quality was significantly poorer in rural Tengua than in Milange, and poor sleep quality was associated with a number of attributes more characteristic of rural areas, including more intense physical labour and less comfortable sleeping arrangements. Thus, whilst our data support the hypothesis that access to electricity delays sleep timing, the higher sleep quality in the urban population also suggests that some aspects of industrialisation are beneficial to sleep.
A portable system for rapid bacterial composition analysis using a nanopore-based sequencer and laptop computer
Authors: Mitsuhashi Satomi , Kryukov Kirill , Nakagawa So , Takeuchi Junko S. , Shiraishi Yoshiki , Asano Koichiro , Imanishi Tadashi
Published: July 2017

We developed a portable system for 16S rDNA analyses consisting of a nanopore technology-based sequencer, the MinION, and laptop computers, and assessed its potential ability to determine bacterial compositions rapidly. We tested our protocols using a mock bacterial community that contained equimolar 16S rDNA and a pleural effusion from a patient with empyema, for time effectiveness and accuracy. MinION sequencing targeting 16S rDNA detected all 20 of the bacterial species present in the mock bacterial community. Time course analysis indicated that the sequence data obtained during the first 5 minutes of sequencing (1,379 bacterial reads) were enough to detect all 20 bacteria in the mock sample and to determine species composition, consistent with results of those obtained from 4 hours of sequencing (24,202 reads). Additionally, using a clinical sample extracted from the empyema patient’s pleural effusion, we could identify major bacterial pathogens in that effusion using our rapid sequencing and analysis protocol. All results are comparable to conventional 16S rDNA sequencing results using an IonPGM sequencer. Our results suggest that rapid sequencing and bacterial composition determination are possible within 2 hours after obtaining a DNA sample.
Assessment of the occurrence, spatiotemporal variations and geoaccumulation of fifty-two inorganic elements in sewage sludge: A sludge management revisit
Authors: Suanon Fidèle , Sun Qian , Yang Xiaoyong , Chi Qiaoqiao , Mulla Sikandar I. , Mama Daouda , Yu Chang-Ping
Published: July 2017

The limited information about the sludge quality has made its management a top environmental challenge. In the present study, occurrence and the spatiotemporal variations of 52 inorganic elements were investigated in the sludge samples from three wastewater treatment plants (WWTPs) in Xiamen city, China. The results showed, the occurrence of 49 elements with the concentrations in the range of >125–53500 mg kg−1 dry sludge (DS) for commonly used industrial metals, 1.22–14.0 mg kg−1 DS for precious metals, and 1.12–439.0 mg kg−1 DS for rare earth elements. The geo-accumulation studies indicated a moderate to high levels of buildup of some elements in the sewage sludge. Principal components analysis (PCA) indicated strong spatial and weak temporal variations in the concentrations of the elements. Therefore, the sludge disposal operations, based on the element concentrations, geoaccumulation and economic potential are suggested for each WWTP. Sludge from W1 and W2 were found suitable for agricultural usage, while that from W3 showed a higher economic potential for the recovery of precious metals. This study concludes that a comprehensive analysis of the elements in the sewage sludge could provide critical information for the disposal and management of the sludge.
Laser-pulse-shape control of seeded QED cascades
Authors: Tamburini Matteo , Di Piazza Antonino , Keitel Christoph H.
Published: July 2017

QED cascades are complex avalanche processes of hard photon emission and electron-positron pair creation driven by ultrastrong electromagnetic fields. They play a fundamental role in astrophysical environments such as a pulsars’ magnetosphere, rendering an earth-based implementation with intense lasers attractive. In the literature, QED cascades were also predicted to limit the attainable intensity in a set-up of colliding laser beams in a tenuous gas such as the residual gas of a vacuum chamber, therefore severely hindering experiments at extreme field intensities. Here, we demonstrate that the onset of QED cascades may be either prevented even at intensities around 1026 W/cm2 with tightly focused laser pulses and low-Z gases, or facilitated at intensities below 1024 W/cm2 with enlarged laser focal areas or high-Z gases. These findings pave the way for the control of novel experiments such as the generation of pure electron-positron-photon plasmas from laser energy, and for probing QED in the extreme-intensity regime where the quantum vacuum becomes unstable.
Evidence of Multi-Domain Morphological Structures in Living Escherichia coli
Authors: Tavaddod Sharareh , Naderi-Manesh Hossein
Published: July 2017

A combination of light-microscopy and image processing was used to elaborate on the fluctuation in the width of the cylindrical part of Escherichia coli at sub-pixel-resolution, and under in vivo conditions. The mean-squared-width-difference along the axial direction of the cylindrical part of a number of bacteria was measured. The results reveal that the cylindrical part of Escherichia coli is composed of multi-domain morphological structures. The length of the domains starts at 150 nm in newborn cells, and linearly increases in length up to 300 nm in aged cells. The fluctuation in the local-cell-widths in each domain is less than the fluctuation of local-cell-widths between different domains. Local cell width correlations along the cell body occur on a length scale of less than 50 nm. This finding could be associated with the flexibility of the cell envelope in the radial versus longitudinal directions.
A Predictive Mathematical Modeling Approach for the Study of Doxorubicin Treatment in Triple Negative Breast Cancer
Authors: McKenna Matthew T. , Weis Jared A. , Barnes Stephanie L. , Tyson Darren R. , Miga Michael I. , Quaranta Vito , Yankeelov Thomas E.
Published: July 2017

Doxorubicin forms the basis of chemotherapy regimens for several malignancies, including triple negative breast cancer (TNBC). Here, we present a coupled experimental/modeling approach to establish an in vitro pharmacokinetic/pharmacodynamic model to describe how the concentration and duration of doxorubicin therapy shape subsequent cell population dynamics. This work features a series of longitudinal fluorescence microscopy experiments that characterize (1) doxorubicin uptake dynamics in a panel of TNBC cell lines, and (2) cell population response to doxorubicin over 30 days. We propose a treatment response model, fully parameterized with experimental imaging data, to describe doxorubicin uptake and predict subsequent population dynamics. We found that a three compartment model can describe doxorubicin pharmacokinetics, and pharmacokinetic parameters vary significantly among the cell lines investigated. The proposed model effectively captures population dynamics and translates well to a predictive framework. In a representative cell line (SUM-149PT) treated for 12 hours with doxorubicin, the mean percent errors of the best-fit and predicted models were 14% (±10%) and 16% (±12%), which are notable considering these statistics represent errors over 30 days following treatment. More generally, this work provides both a template for studies quantitatively investigating treatment response and a scalable approach toward predictions of tumor response in vivo.
Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
Authors: Ravishankar Divyashree , Salamah Maryam , Attina Alda , Pothi Radhika , Vallance Thomas M. , Javed Muhammad , Williams Harry F. , Alzahrani Eman M. S. , Kabova Elena , Vaiyapuri Rajendran , Shankland Kenneth , Gibbins Jonathan , Strohfeldt Katja , Greco Francesca , Osborn Helen M. I. , Vaiyapuri Sakthivel
Published: July 2017

The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents.
Rapid Response of Eastern Mediterranean Deep Sea Microbial Communities to Oil
Authors: Liu Jiang , Techtmann Stephen M. , Woo Hannah L. , Ning Daliang , Fortney Julian L. , Hazen Terry C.
Published: July 2017

Deep marine oil spills like the Deepwater Horizon (DWH) in the Gulf of Mexico have the potential to drastically impact marine systems. Crude oil contamination in marine systems remains a concern, especially for countries around the Mediterranean Sea with off shore oil production. The goal of this study was to investigate the response of indigenous microbial communities to crude oil in the deep Eastern Mediterranean Sea (E. Med.) water column and to minimize potential bias associated with storage and shifts in microbial community structure from sample storage. 16S rRNA amplicon sequencing was combined with GeoChip metagenomic analysis to monitor the microbial community changes to the crude oil and dispersant in on-ship microcosms set up immediately after water collection. After 3 days of incubation at 14 °C, the microbial communities from two different water depths: 824 m and 1210 m became dominated by well-known oil degrading bacteria. The archaeal population and the overall microbial community diversity drastically decreased. Similarly, GeoChip metagenomic analysis revealed a tremendous enrichment of genes related to oil biodegradation, which was consistent with the results from the DWH oil spill. These results highlight a rapid microbial adaption to oil contamination in the deep E. Med., and indicate strong oil biodegradation potential.
In vivo analysis of protein crowding within the nuclear pore complex in interphase and mitosis
Authors: Konishi Hide A. , Asai Suguru , Watanabe Tomonobu M. , Yoshimura Shige H.
Published: July 2017

The central channel of the nuclear pore complex (NPC) is occupied by non-structured polypeptides with a high content of Phe-Gly (FG) motifs. This protein-rich environment functions as an entropic barrier that prevents the passage of molecules, as well as the binding sites for karyopherins, to regulate macromolecular traffic between the nucleoplasm and the cytoplasm. In this study, we expressed individual Nups fused with a crowding-sensitive probe (GimRET) to determine the spatial distribution of protein-rich domains within the central channel in vivo, and characterize the properties of the entropic barrier. Analyses of the probe signal revealed that the central channel contains two protein-rich domains at both the nucleoplasmic and cytoplasmic peripheries, and a less-crowded central cavity. Karyopherins and other soluble proteins are not the constituents of the protein-rich domains. The time-lapse observation of the post-mitotic reassembly process also revealed how individual protein-rich domains are constructed by a sequential assembly of nucleoporins.
Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer
Authors: Lee Eun-Hee , Ji Kon-Young , Kim Eun-Mi , Kim Su-Man , Song Hyeong-Woo , Choi Ha-Rim , Chung Byung Yeoup , Choi Hyo Jin , Bai Hyoung-Woo , Kang Hyung-Sik
Published: July 2017

Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-mediated knockdown of E6 expression led to increased phosphatase and tensin homolog (PTEN) phosphorylation at Ser380 and attenuated AKT phosphorylation. Expression of membrane-associated guanylate kinase inverted-2 (MAGI-2), an E6-induced degradation target, was induced in E6-siRNA-transfected cells. Moreover, myeloid zinc finger protein 1 (MZF1) binds directly to the Axl promoter in HE6F cells. Axl expression was regulated by HPV16E6-mediated PTEN/AKT signalling pathway, and Axl promoter activity was regulated through MZF1 activation in cervical cancer, which promoted malignancy. Axl silencing suppressed the metastasis of Caski cells and enhanced the susceptibility to NK cell-mediated killing of HE6F cells. In addition, the expression of Axl and MZF1 was highly correlated with clinical stage of cervical cancer and HPV16/18 infection. Taken together, Axl expression was induced by HPV16E6 in cervical cancer cells, suggesting that blockade of Axl signalling might be an effective way to reduce the progression of cervical cancer.
Preservative solution that stabilizes erythrocyte morphology and leukocyte viability under ambient conditions
Authors: Sandlin Rebecca D. , Wong Keith H. K. , Boneschansker Leo , Carey Thomas R. , Miller Kathleen L. , Rose Gregory , Haber Daniel A. , Maheswaran Shyamala , Irimia Daniel , Stott Shannon L. , Toner Mehmet
Published: July 2017

The deterioration of whole bloodex vivorepresents a logistical hurdle in clinical and research settings. Here, a cocktail preservative is described that stabilizes leukocyte viability and erythrocyte morphology in whole blood under ambient storage. Neutrophil biostabilization was explored using a sophisticated microfluidic assay to examine the effectiveness of caspase inhibition to stabilize purified neutrophils. Following 72 h ambient storage, neutrophils remained fully functional to migrate towards chemical cues and maintained their ability to undergo NETosis after stimulation. Furthermore, stored neutrophils exhibited improved CD45 biomarker retention and reduced apoptosis and mortality compared to untreated controls. To stabilize erythrocyte morphology, a preservative solution was formulated using Taguchi methods of experimental design, and combined with the caspase inhibitor to form a whole blood cocktail solution, CSWB. CSWBwas evaluated in blood from healthy donors and from women with metastatic breast cancer stored under ambient conditions for 72 h. CSWB-treated samples showed a significant improvement in erythrocyte morphology compared to untreated controls. Leukocytes in CSWB-treated blood exhibited significantly higher viability and CD45 biomarker retention compared to untreated controls. This 72 h shelf life under ambient conditions represents an opportunity to transport isolates or simply ease experimental timelines where blood degradation is problematic.
Percolation-theoretic bounds on the cache size of nodes in mobile opportunistic networks
Authors: Yuan Peiyan , Wu Honghai , Zhao Xiaoyan , Dong Zhengnan
Published: July 2017

The node buffer size has a large influence on the performance of Mobile Opportunistic Networks (MONs). This is mainly because each node should temporarily cache packets to deal with the intermittently connected links. In this paper, we study fundamental bounds on node buffer size below which the network system can not achieve the expected performance such as the transmission delay and packet delivery ratio. Given the condition that each link has the same probability p to be active in the next time slot when the link is inactive and q to be inactive when the link is active, there exists a critical value p
c
from a percolation perspective. If p > p
c
, the network is in the supercritical case, where we found that there is an achievable upper bound on the buffer size of nodes, independent of the inactive probability q. When p < p
c
, the network is in the subcritical case, and there exists a closed-form solution for buffer occupation, which is independent of the size of the network.
A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast
Authors: García Raúl , Bravo Enrique , Diez-Muñiz Sonia , Nombela Cesar , Rodríguez-Peña Jose M. , Arroyo Javier
Published: July 2017

Fungal cells trigger adaptive mechanisms to survive in situations that compromise cell wall integrity. We show here that the global transcriptional response elicited by inhibition of the synthesis of β-1,3-glucan by caspofungin, encompasses a set of genes that are dependent on Slt2, the MAPK of the Cell Wall Integrity (CWI) pathway, and a broad group of genes regulated independently of Slt2. Genes negatively regulated by the cyclic AMP/Protein Kinase A (PKA) signaling pathway were overrepresented in the latter group. Moreover, cell wall stress mediated by inhibition of β-1,3-glucan synthesis, but not by other cell wall interfering compounds, negatively regulated PKA signaling as indicated by the nuclear localisation of Msn2, cellular glycogen accumulation, a decrease of intracellular cAMP levels and a severe decrease in both the activation of the small GTPase Ras2 and the phosphorylation of known substrates of PKA. All these effects relied on the plasma membrane-spanning sensor of the CWI pathway Wsc1. In addition, caspofungin induced a reduction in the cytosolic pH, which was dependent on the extracellular region of Wsc1. Therefore, alterations of the β-1,3-glucan network in the fungal cell wall, induce, through Wsc1, the activation of the CWI pathway and parallel inhibition of PKA signaling.
Quantum Critical Scaling under Periodic Driving
Authors: Lorenzo Salvatore , Marino Jamir , Plastina Francesco , Palma G. Massimo , Apollaro Tony J. G.
Published: July 2017

Universality is key to the theory of phase transitions, stating that the equilibrium properties of observables near a phase transition can be classified according to few critical exponents. These exponents rule an universal scaling behaviour that witnesses the irrelevance of the model’s microscopic details at criticality. Here we discuss the persistence of such a scaling in a one-dimensional quantum Ising model under sinusoidal modulation in time of its transverse magnetic field. We show that scaling of various quantities (concurrence, entanglement entropy, magnetic and fidelity susceptibility) endures up to a stroboscopic time τ
bd
, proportional to the size of the system. This behaviour is explained by noticing that the low-energy modes, responsible for the scaling properties, are resilient to the absorption of energy. Our results suggest that relevant features of the universality do hold also when the system is brought out-of-equilibrium by a periodic driving.
Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families
Authors: Al-Mubarak Bashayer , Abouelhoda Mohamed , Omar Aisha , AlDhalaan Hesham , Aldosari Mohammed , Nester Michael , Alshamrani Hussain. A. , El-Kalioby Mohamed , Goljan Ewa , Albar Renad , Subhani Shazia , Tahir Asma , Asfahani Sultana , Eskandrani Alaa , Almusaiab Ahmed , Magrashi Amna , Shinwari Jameela , Monies Dorota , Al Tassan Nada
Published: July 2017

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with genetic and clinical heterogeneity. The interplay of de novo and inherited rare variants has been suspected in the development of ASD. Here, we applied whole exome sequencing (WES) on 19 trios from singleton Saudi families with ASD. We developed an analysis pipeline that allows capturing both de novo and inherited rare variants predicted to be deleterious. A total of 47 unique rare variants were detected in 17 trios including 38 which are newly discovered. The majority were either autosomal recessive or X-linked. Our pipeline uncovered variants in 15 ASD-candidate genes, including 5 (GLT8D1, HTATSF1, OR6C65, ITIH6 and DDX26B) that have not been reported in any human condition. The remaining variants occurred in genes formerly associated with ASD or other neurological disorders. Examples include SUMF1, KDM5B and MXRA5 (Known-ASD genes), PRODH2 and KCTD21 (implicated in schizophrenia), as well as USP9X and SMS (implicated in intellectual disability). Consistent with expectation and previous studies, most of the genes implicated herein are enriched for biological processes pertaining to neuronal function. Our findings underscore the private and heterogeneous nature of the genetic architecture of ASD even in a population with high consanguinity rates.
Heteroborospherene clusters Nin ∈ B40 (n = 1–4) and heteroborophene monolayers Ni2 ∈ B14 with planar heptacoordinate transition-metal centers in η7-B7 heptagons
Authors: Li Hai-Ru , Tian Xin-Xin , Luo Xue-Mei , Yan Miao , Mu Yue-Wen , Lu Hai-Gang , Li Si-Dian
Published: July 2017

With inspirations from recent discoveries of the cage-like borospherene B40 and perfectly planar Co ∈ B18− and based on extensive global minimum searches and first-principles theory calculations, we present herein the possibility of the novel planar Ni ∈ B18 (1), cage-like heteroborospherenes Nin ∈ B40 (n = 1–4) (2–5), and planar heteroborophenes Ni2 ∈ B14 (6, 7) which all contain planar or quasi-planar heptacoordinate transition-metal (phTM) centers in η7-B7 heptagons. The nearly degenerate Ni2 ∈ B14 (6) and Ni2 ∈ B14 (7) monolayers are predicted to be metallic in nature, with Ni2 ∈ B14 (6) composed of interwoven boron double chains with two phNi centers per unit cell being the precursor of cage-like Nin ∈ B40 (n = 1–4) (2–5). Detailed bonding analyses indicate that Nin ∈ B40 (n = 1–4) (2–5) and Ni2 ∈ B14 (6, 7) possess the universal bonding pattern of σ + π double delocalization on the boron frameworks, with each phNi forming three lone pairs in radial direction (3dz22, 3dzx2, and 3dyz2) and two effective nearly in-plane 8c-2e σ-coordination bonds between the remaining tangential Ni 3d orbitals (3dx2−y2 and 3dxy) and the η7-B7 heptagon around it. The IR, Raman, and UV-vis absorption spectra of 1–5 are computationally simulated to facilitate their experimental characterizations.
Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse
Authors: Gargini Claudia , Novelli Elena , Piano Ilaria , Biagioni Martina , Strettoi Enrica
Published: July 2017

Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of RhoTvrm4/Rho+ rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.
Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers
Authors: Cong Yingying , Kriegenburg Franziska , de Haan Cornelis A. M. , Reggiori Fulvio
Published: July 2017

Coronaviruses (CoV) are enveloped viruses and rely on their nucleocapsid N protein to incorporate the positive-stranded genomic RNA into the virions. CoV N proteins form oligomers but the mechanism and relevance underlying their multimerization remain to be fully understood. Using in vitro pull-down experiments and density glycerol gradients, we found that at least 3 regions distributed over its entire length mediate the self-interaction of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) N protein. The fact that these regions can bind reciprocally between themselves provides a possible molecular basis for N protein oligomerization. Interestingly, cytoplasmic N molecules of MHV-infected cells constitutively assemble into oligomers through a process that does not require binding to genomic RNA. Based on our data, we propose a model where constitutive N protein oligomerization allows the optimal loading of the genomic viral RNA into a ribonucleoprotein complex via the presentation of multiple viral RNA binding motifs.
Dual-band wide-angle metamaterial perfect absorber based on the combination of localized surface plasmon resonance and Helmholtz resonance
Authors: Zhang Changlei , Huang Cheng , Pu Mingbo , Song Jiakun , Zhao Zeyu , Wu Xiaoyu , Luo Xiangang
Published: July 2017

In this article, a dual-band wide-angle metamaterial perfect absorber is proposed to achieve absorption at the wavelength where laser radar operates. It is composed of gold ring array and a Helmholtz resonance cavity spaced by a Si dielectric layer. Numerical simulation results reveal that the designed absorber displays two absorption peaks at the target wavelength of 10.6 μm and 1.064 μm with the large frequency ratio and near-unity absorptivity under the normal incidence. The wide-angle absorbing property and the polarization-insensitive feature are also demonstrated. Localized surface plasmons resonance and Helmholtz resonance are introduced to analyze and interpret the absorbing mechanism. The designed perfect absorber can be developed for potential applications in infrared stealth field.
Visualization of kidney fibrosis in diabetic nephropathy by long diffusion tensor imaging MRI with spin-echo sequence
Authors: Kaimori Jun-Ya , Isaka Yoshitaka , Hatanaka Masaki , Yamamoto Satoko , Ichimaru Naotsugu , Fujikawa Akihiko , Shibata Hiroshi , Fujimori Akira , Miyoshi Sosuke , Yokawa Takashi , Kuroda Kagayaki , Moriyama Toshiki , Rakugi Hiromi , Takahara Shiro
Published: July 2017

Renal fibrosis (RF) is an indicator for progression of chronic kidney disease (CKD). Although diabetic nephropathy (DN) is the leading cause of CKD and end-stage renal disease in Western populations, the ability of MRI to evaluate RF in DN patients has not been determined. As a first step to identify possible MRI methods for RF evaluation, we examined the use of diffusion tensor imaging (DTI) MRI to evaluate RF in a rat model of DN (SHR/NDmcr-cp(cp/cp): SHR/ND). The signal-to-noise ratio in DTI MRI was enhanced using a spin-echo sequence, and a special kidney attachment was developed for long-term stabilization. The changes in renal temperature and blood flow during measurement were minimal, suggesting the feasibility of this method. At 38 weeks of age, RF had aggressively accumulated in the outer stripe (OS) of the outer medulla. FA maps showed that this method was successful in visualizing and evaluating fibrosis in the OS of the SHR/ND rat kidney (r = 0.7697, P = 0.0126). Interestingly, in the FA color maps, the directions of water molecule diffusion in RF were random, but distinct from conventional water diffusion in brain neuron fibers. These findings indicate that DTI MRI may be able to evaluate RF in CKD by DN.
Parameter determination and transformation for the focusing of dielectric microspheres illuminated by optical needle
Authors: Xia Tongnan , Guo Hanming , Hu Jinbing , Zhuang Songlin
Published: July 2017

By eliminating the spherical aberrations of microsphere we derived a simple but useful formula on the focusing of dielectric microsphere. On basis of this formula, not only can researchers determine the parameters of an optical microsphere system with super-resolution, but they can also perform parameter transformation. In order to facilitate the application, the principle of parameter transformation was summarized into three kinds of case listed in Table 1, which were all demonstrated numerically with concrete examples by finite-difference time-domain method. This formula will be conducive to the development of applications based on microsphere, such as photonic nano-jet lithography, microsphere nano-scope.
The lower pT limit of deep hydrocarbon synthesis by CaCO3 aqueous reduction
Authors: Mukhina E. , Kolesnikov A. , Kutcherov V.
Published: July 2017

The deep abiogenic synthesis of hydrocarbons is possible under the conditions of the asthenosphere. We have found that this process can also occur under the mineral and thermobaric conditions of subducting slabs. We have investigated the abiogenic synthesis of hydrocarbon systems at pressures of 2.0–6.6 GPa and temperatures of 250–600 °C. The determined lower thermobaric limit of the reaction at 280–300 °C and 2–3 GPa corresponds to a depth of 70–80 km during cold subduction. The hydrocarbon fluid formed in the slab can migrate upwards through the network of faults and fractures to form petroleum deposits.
EEG machine learning for accurate detection of cholinergic intervention and Alzheimer’s disease
Authors: Simpraga Sonja , Alvarez-Jimenez Ricardo , Mansvelder Huibert D. , van Gerven Joop M. A. , Groeneveld Geert Jan , Poil Simon-Shlomo , Linkenkaer-Hansen Klaus
Published: July 2017

Monitoring effects of disease or therapeutic intervention on brain function is increasingly important for clinical trials, albeit hampered by inter-individual variability and subtle effects. Here, we apply complementary biomarker algorithms to electroencephalography (EEG) recordings to capture the brain’s multi-faceted signature of disease or pharmacological intervention and use machine learning to improve classification performance. Using data from healthy subjects receiving scopolamine we developed an index of the muscarinic acetylcholine receptor antagonist (mAChR) consisting of 14 EEG biomarkers. This mAChR index yielded higher classification performance than any single EEG biomarker with cross-validated accuracy, sensitivity, specificity and precision ranging from 88–92%. The mAChR index also discriminated healthy elderly from patients with Alzheimer’s disease (AD); however, an index optimized for AD pathophysiology provided a better classification. We conclude that integrating multiple EEG biomarkers can enhance the accuracy of identifying disease or drug interventions, which is essential for clinical trials.
Two-photon interference of polarization-entangled photons in a Franson interferometer
Authors: Kim Heonoh , Lee Sang Min , Kwon Osung , Moon Han Seb
Published: July 2017

We present two-photon interference experiments with polarization-entangled photon pairs in a polarization-based Franson-type interferometer. Although the two photons do not meet at a common beamsplitter, a phase-insensitive Hong-Ou-Mandel type two-photon interference peak and dip fringes are observed, resulting from the two-photon interference effect between two indistinguishable two-photon probability amplitudes leading to a coincidence detection. A spatial quantum beating fringe is also measured for nondegenerate photon pairs in the same interferometer, although the two-photon states have no frequency entanglement. When unentangled polarization-correlated photons are used as an input state, the polarization entanglement is successfully recovered through the interferometer via delayed compensation.
Associating transcription factors and conserved RNA structures with gene regulation in the human brain
Authors: Hecker Nikolai , Seemann Stefan E. , Silahtaroglu Asli , Ruzzo Walter L. , Gorodkin Jan
Published: July 2017

Anatomical subdivisions of the human brain can be associated with different neuronal functions. This functional diversification is reflected by differences in gene expression. By analyzing post-mortem gene expression data from the Allen Brain Atlas, we investigated the impact of transcription factors (TF) and RNA secondary structures on the regulation of gene expression in the human brain. First, we modeled the expression of a gene as a linear combination of the expression of TFs. We devised an approach to select robust TF-gene interactions and to determine localized contributions to gene expression of TFs. Among the TFs with the most localized contributions, we identified EZH2 in the cerebellum, NR3C1 in the cerebral cortex and SRF in the basal forebrain. Our results suggest that EZH2 is involved in regulating ZIC2 and SHANK1 which have been linked to neurological diseases such as autism spectrum disorder. Second, we associated enriched regulatory elements inside differentially expressed mRNAs with RNA secondary structure motifs. We found a group of purine-uracil repeat RNA secondary structure motifs plus other motifs in neuron related genes such as ACSL4 and ERLIN2.
p32 heterozygosity protects against age- and diet-induced obesity by increasing energy expenditure
Authors: Liu Yong , Leslie Patrick L. , Jin Aiwen , Itahana Koji , Graves Lee M. , Zhang Yanping
Published: July 2017

Obesity is increasing in prevalence and has become a global public health problem. The main cause of obesity is a perturbation in energy homeostasis, whereby energy intake exceeds energy expenditure. Although mitochondrial dysfunction has been linked to the deregulation of energy homeostasis, the precise mechanism is poorly understood. Here, we identify mitochondrial p32 (also known as C1QBP) as an important regulator of lipid homeostasis that regulates both aerobic and anaerobic energy metabolism. We show that while whole-body deletion of the p32 results in an embryonic lethal phenotype, mice heterozygous for p32 are resistant to age- and high-fat diet-induced ailments, including obesity, hyperglycemia, and hepatosteatosis. Notably, p32+/− mice are apparently healthy, demonstrate an increased lean-to-fat ratio, and show dramatically improved insulin sensitivity despite prolonged high-fat diet feeding. The p32+/− mice show increased oxygen consumption and heat production, indicating that they expend more energy. Our analysis revealed that haploinsufficiency for p32 impairs glucose oxidation, which results in a compensatory increase in fatty acid oxidation and glycolysis. These metabolic alterations increase both aerobic and anaerobic energy expenditure. Collectively, our data show that p32 plays a critical role in energy homeostasis and represents a potential novel target for the development of anti-obesity drugs.
Effect of head group and lipid tail oxidation in the cell membrane revealed through integrated simulations and experiments
Authors: Yusupov M. , Wende K. , Kupsch S. , Neyts E. C. , Reuter S. , Bogaerts A.
Published: July 2017

We report on multi-level atomistic simulations for the interaction of reactive oxygen species (ROS) with the head groups of the phospholipid bilayer, and the subsequent effect of head group and lipid tail oxidation on the structural and dynamic properties of the cell membrane. Our simulations are validated by experiments using a cold atmospheric plasma as external ROS source. We found that plasma treatment leads to a slight initial rise in membrane rigidity, followed by a strong and persistent increase in fluidity, indicating a drop in lipid order. The latter is also revealed by our simulations. This study is important for cancer treatment by therapies producing (extracellular) ROS, such as plasma treatment. These ROS will interact with the cell membrane, first oxidizing the head groups, followed by the lipid tails. A drop in lipid order might allow them to penetrate into the cell interior (e.g., through pores created due to oxidation of the lipid tails) and cause intracellular oxidative damage, eventually leading to cell death. This work in general elucidates the underlying mechanisms of ROS interaction with the cell membrane at the atomic level.