bluuebunny/crossref_metadata_2025 huggingface dataset:
A multistage rotational speed changing molecular rotor regulated by pH and metal cations
Authors: Wu Yingying , Wang Guangxia , Li Qiaolian , Xiang Junfeng , Jiang Hua , Wang Ying
Published: May 2018

Despite having significant applications in building nanomachines, molecular rotors with the rotational speed modulations to multiple stages in a wide range of frequency have not yet been well established. Here, we report the discovery of a stimuli-responsive molecular rotor, the rotational speed of which in the slow-to-fast range could be modulated to at least four stages triggered by acid/base and metal cations. The rotor itself rotates rapidly at ambient or elevated temperature but displays a restricted rotation after deprotonation due to the produced intramolecular electrostatic repulsion. Subsequent addition of Li+ or Na+ cations introduces an electrostatic bridge to stabilize the transition state of the deprotonated rotor, thus giving a cation-radius-dependent acceleration of the rotation to render the rotor running at a mid-speed. All the stimuli are highly reversible. Our studies provide a conceptual approach for constructing multistage rotational-speed-changing molecular rotors, and further, the practical nanomachines.
Organic matter loading by hippopotami causes subsidy overload resulting in downstream hypoxia and fish kills
Authors: Dutton Christopher L. , Subalusky Amanda L. , Hamilton Stephen K. , Rosi Emma J. , Post David M.
Published: May 2018

Organic matter and nutrient loading into aquatic ecosystems affects ecosystem structure and function and can result in eutrophication and hypoxia. Hypoxia is often attributed to anthropogenic pollution and is not common in unpolluted rivers. Here we show that organic matter loading from hippopotami causes the repeated occurrence of hypoxia in the Mara River, East Africa. We documented 49 high flow events over 3 years that caused dissolved oxygen decreases, including 13 events resulting in hypoxia, and 9 fish kills over 5 years. Evidence from experiments and modeling demonstrates a strong mechanistic link between the flushing of hippo pools and decreased dissolved oxygen in the river. This phenomenon may have been more widespread throughout Africa before hippopotamus populations were severely reduced. Frequent hypoxia may be a natural part of tropical river ecosystem function, particularly in rivers impacted by large wildlife.
A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell
Authors: Okamoto Yasunori , Kojima Ryosuke , Schwizer Fabian , Bartolami Eline , Heinisch Tillmann , Matile Stefan , Fussenegger Martin , Ward Thomas R.
Published: May 2018

Complementing enzymes in their native environment with either homogeneous or heterogeneous catalysts is challenging due to the sea of functionalities present within a cell. To supplement these efforts, artificial metalloenzymes are drawing attention as they combine attractive features of both homogeneous catalysts and enzymes. Herein we show that such hybrid catalysts consisting of a metal cofactor, a cell-penetrating module, and a protein scaffold are taken up into HEK-293T cells where they catalyze the uncaging of a hormone. This bioorthogonal reaction causes the upregulation of a gene circuit, which in turn leads to the expression of a nanoluc-luciferase. Relying on the biotin–streptavidin technology, variation of the biotinylated ruthenium complex: the biotinylated cell-penetrating poly(disulfide) ratio can be combined with point mutations on streptavidin to optimize the catalytic uncaging of an allyl-carbamate-protected thyroid hormone triiodothyronine. These results demonstrate that artificial metalloenzymes offer highly modular tools to perform bioorthogonal catalysis in live HEK cells.
A Five-microRNA Signature for Survival Prognosis in Pancreatic Adenocarcinoma based on TCGA Data
Authors: Shi Xiu-Hui , Li Xu , Zhang Hang , He Rui-Zhi , Zhao Yan , Zhou Min , Pan Shu-Tao , Zhao Chun-Le , Feng Ye-Chen , Wang Min , Guo Xing-Jun , Qin Ren-Yi
Published: May 2018

Novel biomarkers for pancreatic adenocarcinoma are urgently needed because of its poor prognosis. Here, by using The Cancer Genome Atlas (TCGA) RNA-seq data, we evaluated the prognostic values of the differentially expressed miRNAs and constructed a five-miRNA signature that could effectively predict patient overall survival (OS). The Kaplan-Meier overall survival curves of two groups based on the five miRNAs were notably different, showing overall survival in 10.2% and 47.8% at five years for patients in high-risk and low-risk groups, respectively. The ROC curve analysis achieved AUC of 0.775, showing good sensitivity and specificity of the five-miRNA signature model in predicting pancreatic adenocarcinoma patient survival risk. The functional enrichment analysis suggested that the target genes of the miRNA signature may be involved in various pathways related to cancer, including PI3K-Akt, TGF-β, and pluripotent stem cell signaling pathways. Finally, we analyzed expression of the five specific miRNAs in the miRNA signature, and validated the reliability of the results in 20 newly diagnosed pancreatic adenocarcinoma patients using qRT-PCR. The expression results of qRT-PCR were consistent with the TCGA results. Taken together, these findings suggested that the five-miRNA signature (hsa-miR-203, hsa-miR-424, hsa-miR-1266 hsa-miR-1293, and hsa-miR-4772) could be used as a prognostic marker for pancreatic adenocarcinoma.
Author Correction: Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis
Authors: Srinivasan Sundararajan , Severa Martina , Rizzo Fabiana , Menon Ramesh , Brini Elena , Mechelli Rosella , Martinelli Vittorio , Hertzog Paul , Salvetti Marco , Furlan Roberto , Martino Gianvito , Comi Giancarlo , Coccia Eliana M. , Farina Cinthia
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Publisher Correction: HilD and PhoP independently regulate the expression of grhD1, a novel gene required for Salmonella Typhimurium invasion of host cells
Authors: Banda María M. , López Carolina , Manzo Rubiceli , Rico-Pérez Gadea , García Pablo , Rosales-Reyes Roberto , De la Cruz Miguel A. , Soncini Fernando C. , García-del Portillo Francisco , Bustamante Víctor H.
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Expressed repetitive elements are broadly applicable reference targets for normalization of reverse transcription-qPCR data in mice
Authors: Renard Marjolijn , Vanhauwaert Suzanne , Vanhomwegen Marine , Rihani Ali , Vandamme Niels , Goossens Steven , Berx Geert , Van Vlierberghe Pieter , Haigh Jody J. , Decaesteker Bieke , Van Laere Jolien , Lambertz Irina , Speleman Frank , Vandesompele Jo , Willaert Andy
Published: May 2018

Reverse transcription quantitative PCR (RT-qPCR) is the gold standard method for gene expression analysis on mRNA level. To remove experimental variation, expression levels of the gene of interest are typically normalized to the expression level of stably expressed endogenous reference genes. Identifying suitable reference genes and determining the optimal number of reference genes should precede each quantification study. Popular reference genes are not necessarily stably expressed in the examined conditions, possibly leading to inaccurate results. Stably and universally expressed repetitive elements (ERE) have previously been shown to be an excellent alternative for normalization using classic reference genes in human and zebrafish samples. Here, we confirm that in mouse tissues, EREs are broadly applicable reference targets for RT-qPCR normalization, provided that the RNA samples undergo a thorough DNase treatment. We identifiedOrr1a0,Rltr2aiap, andRltr13a3as the most stably expressed mouse EREs across six different experimental conditions. Therefore, we propose this set of ERE reference targets as good candidates for normalization of RT-qPCR data in a plethora of conditions. The identification of widely applicable stable mouse RT-qPCR reference targets for normalization has great potential to facilitate future murine gene expression studies and improve the validity of RT-qPCR data.
Heterologous mammalian Akt disrupts plasma membrane homeostasis by taking over TORC2 signaling in Saccharomyces cerevisiae
Authors: Rodríguez-Escudero Isabel , Fernández-Acero Teresa , Cid Víctor J. , Molina María
Published: May 2018

The Akt protein kinase is the main transducer of phosphatidylinositol-3,4,5-trisphosphate (PtdIns3,4,5P3) signaling in higher eukaryotes, controlling cell growth, motility, proliferation and survival. By co-expression of mammalian class I phosphatidylinositol 3-kinase (PI3K) and Akt in the Saccharomyces cerevisiae heterologous model, we previously described an inhibitory effect on yeast growth that relied on Akt kinase activity. Here we report that PI3K-Akt expression in yeast triggers the formation of large plasma membrane (PM) invaginations that were marked by actin patches, enriched in PtdIns4,5P2 and associated to abnormal intracellular cell wall deposits. These effects of Akt were mimicked by overproduction of the PtdIns4,5P2 effector Slm1, an adaptor of the Ypk1 and Ypk2 kinases in the TORC2 pathway. Although Slm1 was phosphorylated in vivo by Akt, TORC2-dependent Ypk1 activation did not occur. However, PI3K-activated Akt suppressed the lethality derived from inactivation of either TORC2 or Ypk protein kinases. Thus, heterologous co-expression of PI3K and Akt in yeast short-circuits PtdIns4,5P2- and TORC2-signaling at the level of the Slm-Ypk complex, overriding some of its functions. Our results underscore the importance of phosphoinositide-dependent kinases as key actors in the homeostasis and dynamics of the PM.
Transcriptome Analysis of Circulating PBMCs to Understand Mechanism of High Altitude Adaptation in Native Cattle of Ladakh Region
Authors: Verma Preeti , Sharma Ankita , Sodhi Monika , Thakur Kiran , Kataria Ranjit S. , Niranjan Saket K. , Bharti Vijay K. , Kumar Prabhat , Giri Arup , Kalia Sahil , Mukesh Manishi
Published: May 2018

Ladakhi cattle is native population of Leh and Ladakh region and constantly exposed to hypobaric hypoxia over many generations. In present study, transcriptome signatures of cattle from Ladakh region (~5500 m) and Sahiwal cattle from tropical regions were evaluated using Agilent 44 K microarray chip. The top up-regulated genes in Ladakhi cows were INHBC, ITPRI, HECA, ABI3, GPR171, and HIF-1α involved in hypoxia and stress response. In Sahiwal cows, the top up-regulated genes eEF1A1, GRO1, CXCL2, DEFB3 and BOLA-DQA3 were associated with immune function and inflammatory response indicating their strong immune potential to combat the pathogens prevalent in the tropical conditions. The molecular pathways highly impacted were MAPK signaling, ETC, apoptosis, TLR signaling and NF- kB signaling pathway indicating signatures of adaptive evolution of these two cattle types in response to diverse environments. Further, qPCR analysis revealed increased expression of DEGs such as HIF-1, EPAS-1, VEGFA, NOS2, and GLUT-1/SLC2A1 in cattle types from high altitude suggesting their pivotal role in association with high altitude adaptation. Based on data generated, native cattle of Ladakh region was found to be genetically distinct from native cattle adapted to the tropical region of India.
modCHIMERA: a novel murine closed-head model of moderate traumatic brain injury
Authors: Sauerbeck A. D. , Fanizzi C. , Kim J. H. , Gangolli M. , Bayly P. V. , Wellington C. L. , Brody D. L. , Kummer T. T.
Published: May 2018

Traumatic brain injury is a major source of global disability and mortality. Preclinical TBI models are a crucial component of therapeutic investigation. We report a tunable, monitored model of murine non-surgical, diffuse closed-head injury—modCHIMERA—characterized by impact as well as linear and rotational acceleration. modCHIMERA is based on the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) platform. We tested this model at 2 energy levels: 1.7 and 2.1 Joules—substantially higher than previously reported for this system. Kinematic analysis demonstrated linear acceleration exceeding injury thresholds in humans, although outcome metrics tracked impact energy more closely than kinematic parameters. Acute severity metrics were consistent with a complicated-mild or moderate TBI, a clinical population characterized by high morbidity but potentially reversible pathology. Axonal injury was multifocal and bilateral, neuronal death was detected in the hippocampus, and microglial neuroinflammation was prominent. Acute functional analysis revealed prolonged post-injury unconsciousness, and decreased spontaneous behavior and stimulated neurological scores. Neurobehavioral deficits were demonstrated in spatial learning/memory and socialization at 1-month. The overall injury profile of modCHIMERA corresponds with the range responsible for a substantial portion of TBI-related disability in humans. modCHIMERA should provide a reliable platform for efficient analysis of TBI pathophysiology and testing of treatment modalities.
Parallel odor processing by mitral and middle tufted cells in the olfactory bulb
Authors: Cavarretta Francesco , Burton Shawn D. , Igarashi Kei M. , Shepherd Gordon M. , Hines Michael L. , Migliore Michele
Published: May 2018

The olfactory bulb (OB) transforms sensory input into spatially and temporally organized patterns of activity in principal mitral (MC) and middle tufted (mTC) cells. Thus far, the mechanisms underlying odor representations in the OB have been mainly investigated in MCs. However, experimental findings suggest that MC and mTC may encode parallel and complementary odor representations. We have analyzed the functional roles of these pathways by using a morphologically and physiologically realistic three-dimensional model to explore the MC and mTC microcircuits in the glomerular layer and deeper plexiform layer. The model makes several predictions. MCs and mTCs are controlled by similar computations in the glomerular layer but are differentially modulated in deeper layers. The intrinsic properties of mTCs promote their synchronization through a common granule cell input. Finally, the MC and mTC pathways can be coordinated through the deep short-axon cells in providing input to the olfactory cortex. The results suggest how these mechanisms can dynamically select the functional network connectivity to create the overall output of the OB and promote the dynamic synchronization of glomerular units for any given odor stimulus.
Effects of the Th2-dominant milieu on allergic responses in Der f 1-activated mouse basophils and mast cells
Authors: Yi Myung-hee , Kim Hyoung-Pyo , Jeong Kyoung Yong , Kim Ju Yeong , Lee In-Yong , Yong Tai-Soon
Published: May 2018

Although basophils and mast cells share similar phenotypic and functional properties, little is known about the difference in the initial Th2 immune responses of these cells following exposure to proteolytic allergens. Here, we investigated the mechanisms of Th2-mediated immune responses in mouse bone marrow-derived basophils (BMBs) and mast cells (BMMCs) via stimulation with the cysteine protease allergen Der f 1. Our results showed that Th2 cytokines were induced from BMBs by active recombinant Der f 1 (rDer f 1 independently with Toll-like receptor (TLR) 2 and TLR4. Although both BMBs and BMMCs expressed protease-activated receptors on their surfaces, PAR expression following exposure to rDer f 1 was altered only in basophils. G protein-coupled receptors in basophils were found to be associated with interleukin (IL)-4 and IL-13 production from BMBs upon Der f 1 treatment. Secretion of Th2 cytokines from rDer f 1-treated basophils was mediated by G protein βγ and phosphatidylinositol 3-kinase γ through the extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways. These findings provide insights into the roles of cysteine proteases in Th2 immune responses, such as allergic diseases, and improve our understanding of the mechanisms of Th2 cytokine production.
Integrated analysis of hepatic mRNA and miRNA profiles identified molecular networks and potential biomarkers of NAFLD
Authors: Zhu Mingzhe , Wang Qianlei , Zhou Wenjun , Liu Tao , Yang Lili , Zheng Peiyong , Zhang Li , Ji Guang
Published: May 2018

To enhance our understanding of molecular mechanisms and mine novel biomarkers of non-alcoholic fatty liver disease (NAFLD), RNA sequencing was performed to gain hepatic expression profiles of mRNAs and miRNAs in NAFLD and normal rats. Using DESeq with thresholds of a two-fold change and a false discovery rate (FDR) less than 0.05, 336 mRNAs and 21 miRNAs were identified as differentially expressed. Among those, 17 miRNAs (e.g., miR-144-3p, miR-99a-3p, miR-200b-3p, miR-200b-5p, miR-200c-3p, etc.) might serve as novel biomarkers of NAFLD. MiRNA target genes (13565) were predicted by the miRWalk database. Using DAVID 6.8, the intersection (195 genes) of differentially expressed mRNAs and miRNA-predicted target genes were enriched in 47 gene ontology (GO) terms and 28 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Using Cytoscape, pathway interaction and protein-protein interaction (PPI) networks were constructed, and hub genes (e.g., Abcg8, Cyp1a1, Cyp51, Hmgcr, etc.) associated with NAFLD were obtained. Moreover, 673 miRNA-mRNA negative regulatory pairs were obtained, and networks were constructed. Finally, several representative miRNAs and mRNAs were validated by real-time qPCR. In conclusion, potential molecular mechanisms of NAFLD could be inferred from integrated analysis of mRNA and miRNA profiles, which may indicate novel biomarkers of NAFLD.
High-speed Fourier ptychographic microscopy based on programmable annular illuminations
Authors: Sun Jiasong , Zuo Chao , Zhang Jialin , Fan Yao , Chen Qian
Published: May 2018

High-throughput quantitative phase imaging (QPI) is essential to cellular phenotypes characterization as it allows high-content cell analysis and avoids adverse effects of staining reagents on cellular viability and cell signaling. Among different approaches, Fourier ptychographic microscopy (FPM) is probably the most promising technique to realize high-throughput QPI by synthesizing a wide-field, high-resolution complex image from multiple angle-variably illuminated, low-resolution images. However, the large dataset requirement in conventional FPM significantly limits its imaging speed, resulting in low temporal throughput. Moreover, the underlying theoretical mechanism as well as optimum illumination scheme for high-accuracy phase imaging in FPM remains unclear. Herein, we report a high-speed FPM technique based on programmable annular illuminations (AIFPM). The optical-transfer-function (OTF) analysis of FPM reveals that the low-frequency phase information can only be correctly recovered if the LEDs are precisely located at the edge of the objective numerical aperture (NA) in the frequency space. By using only 4 low-resolution images corresponding to 4 tilted illuminations matching a 10×, 0.4 NA objective, we present the high-speed imaging results of in vitro Hela cells mitosis and apoptosis at a frame rate of 25 Hz with a full-pitch resolution of 655 nm at a wavelength of 525 nm (effective NA = 0.8) across a wide field-of-view (FOV) of 1.77 mm2, corresponding to a space–bandwidth–time product of 411 megapixels per second. Our work reveals an important capability of FPM towards high-speed high-throughput imaging of in vitro live cells, achieving video-rate QPI performance across a wide range of scales, both spatial and temporal.
Genomic alterations of ground-glass nodular lung adenocarcinoma
Authors: Lee Hyun , Joung Je-Gun , Shin Hyun-Tae , Kim Duk-Hwan , Kim Yujin , Kim Hojoong , Kwon O. Jung , Shim Young Mog , Lee Ho Yun , Lee Kyung Soo , Choi Yoon-La , Park Woong-Yang , Hayes D. Neil , Um Sang-Won
Published: May 2018

In-depth molecular pathogenesis of ground-glass nodular lung adenocarcinoma has not been well understood. The objectives of this study were to identify genomic alterations in ground-glass nodular lung adenocarcinomas and to investigate whether viral transcripts were detected in these tumors. Nine patients with pure (n = 4) and part-solid (n = 5) ground-glass nodular adenocarcinomas were included. Six were females with a median age of 58 years. We performed targeted exon sequencing and RNA sequencing. EGFR (n = 10), IDH2 (n = 2), TP53 (n = 1), PTEN (n = 1), EPHB4 (n = 1), and BRAF (n = 1) were identified as driver mutations by targeted exon sequencing. Vasculogenesis-associated genes including NOTCH4 and TGFBR3 expression were significantly downregulated in adenocarcinoma tissue versus normal tissue (adjusted P values < 0.001 for both NOTCH4 and TGFBR3). In addition, five novel fusion gene loci were identified in four lung adenocarcinomas. However, no significant virus-associated transcripts were detected in tumors. In conclusions, EGFR, IDH2, TP53, PTEN, EPHB4, and BRAF were identified as putative driver mutations of ground-glass nodular adenocarcinomas. Five novel fusion genes were also identified in four tumors. Viruses do not appear to be involved in the tumorigenesis of ground-glass nodular lung adenocarcinoma.
High-resolution Imaging of Myeloperoxidase Activity Sensors in Human Cerebrovascular Disease
Authors: Wadghiri Youssef Z. , Hoang Dung Minh , Leporati Anita , Gounis Matthew J. , Rodríguez-Rodríguez Aurora , Mazzanti Mary L. , Weaver John P. , Wakhloo Ajay K. , Caravan Peter , Bogdanov Alexei A.
Published: May 2018

Progress in clinical development of magnetic resonance imaging (MRI) substrate-sensors of enzymatic activity has been slow partly due to the lack of human efficacy data. We report here a strategy that may serve as a shortcut from bench to bedside. We tested ultra high-resolution 7T MRI (µMRI) of human surgical histology sections in a 3-year IRB approved, HIPAA compliant study of surgically clipped brain aneurysms. µMRI was used for assessing the efficacy of MRI substrate-sensors that detect myeloperoxidase activity in inflammation. The efficacy of Gd-5HT-DOTAGA, a novel myeloperoxidase (MPO) imaging agent synthesized by using a highly stable gadolinium (III) chelate was tested both in tissue-like phantoms and in human samples. After treating histology sections with paramagnetic MPO substrate-sensors we observed relaxation time shortening and MPO activity-dependent MR signal enhancement. An increase of normalized MR signal generated by ultra-short echo time MR sequences was corroborated by MPO activity visualization by using a fluorescent MPO substrate. The results of µMRI of MPO activity associated with aneurysmal pathology and immunohistochemistry demonstrated active involvement of neutrophils and neutrophil NETs as a result of pro-inflammatory signalling in the vascular wall and in the perivascular space of brain aneurysms.
Solid dissolution in a fluid solvent is characterized by the interplay of surface area-dependent diffusion and physical fragmentation
Authors: Seager R. J. , Acevedo Andrew J. , Spill Fabian , Zaman Muhammad H.
Published: May 2018

The processes of dissolution and fragmentation have high relevance in pharmaceutical research, medicine, digestive physiology, and engineering design. Experimentally, dissolution and fragmentation are observed to occur simultaneously, yet little is known about the relative importance of each of these processes and their impact on the dissolution process as a whole. Thus, in order to better explain these phenomena and the manner in which they interact, we have developed a novel mathematical model of dissolution, based on partial differential equations, taking into consideration the two constituent processes of surface area-dependent diffusive mass removal and physical fragmentation of the solid particles, and the basic physical laws governing these processes. With this model, we have been able to quantify the effects of the interplay between these two processes and determine the optimal conditions for rapid solid dissolution in liquid solvents. We were able to reproduce experimentally observed phenomena and simulate dissolution under a wide range of experimentally occurring conditions to give new perspectives into the kinetics of this common, yet complex process. Finally, we demonstrated the utility of this model to aid in experiment and device design as an optimisation tool.
A grazing Gomphotherium in Middle Miocene Central Asia, 10 million years prior to the origin of the Elephantidae
Authors: Wu Yan , Deng Tao , Hu Yaowu , Ma Jiao , Zhou Xinying , Mao Limi , Zhang Hanwen , Ye Jie , Wang Shi-Qi
Published: May 2018

Feeding preference of fossil herbivorous mammals, concerning the coevolution of mammalian and floral ecosystems, has become of key research interest. In this paper, phytoliths in dental calculus from two gomphotheriid proboscideans of the middle Miocene Junggar Basin, Central Asia, have been identified, suggesting that Gomphotherium connexum was a mixed feeder, while the phytoliths from G. steinheimense indicates grazing preference. This is the earliest-known proboscidean with a predominantly grazing habit. These results are further confirmed by microwear and isotope analyses. Pollen record reveals an open steppic environment with few trees, indicating an early aridity phase in the Asian interior during the Mid-Miocene Climate Optimum, which might urge a diet remodeling of G. steinheimense. Morphological and cladistic analyses show that G. steinheimense comprises the sister taxon of tetralophodont gomphotheres, which were believed to be the general ancestral stock of derived “true elephantids”; whereas G. connexum represents a more conservative lineage in both feeding behavior and tooth morphology, which subsequently became completely extinct. Therefore, grazing by G. steinheimense may have acted as a behavior preadaptive for aridity, and allowing its lineage evolving new morphological features for surviving later in time. This study displays an interesting example of behavioral adaptation prior to morphological modification.
GmBEHL1, a BES1/BZR1 family protein, negatively regulates soybean nodulation
Authors: Yan Qiqi , Wang Lixiang , Li Xia
Published: May 2018

Brassinosteroids (BRs) play an essential role in plant growth, and BRI1-EMS suppressor 1 (BES1)/brassinazole-resistant 1 (BZR1) family transcription factors integrate a variety of plant signaling pathways. Despite the fact that BRs inhibit nodulation in leguminous plants, how BRs modulate rhizobia-host interactions and nodule morphogenesis is unknown. Here, we show that GmBEHL1, a soybean homolog of Arabidopsis BES1/BZR1 homolog 1 (BEH1), is an interacting partner of Nodule Number Control 1, a transcriptional repressor that mediates soybean nodulation. GmBEHL1 was highly expressed at the basal parts of emerging nodules, and its expression gradually expanded during nodule maturation. The overexpression and downregulation of GmBEHL1 inhibited and enhanced the number of nodules, respectively, in soybean. Intriguingly, alterations in GmBEHL1 expression repressed the expression of genes in the BR biosynthesis pathway, including homologs of Arabidopsis Constitutive Photomorphogenesis and Dwarf and Dwarf 4. We also detected an interaction between GmBEHL1 and GmBIN2, a putative BR-insensitive 2 (BIN2) homolog, in soybean. Moreover, BR treatment reduced the number, but increased the size, of soybean nodules. Our results reveal GmBEHL1 to be a potent gene that integrates BR signaling with nodulation signaling pathways to regulate symbiotic nodulation.
Motion compensated micro-CT reconstruction for in-situ analysis of dynamic processes
Authors: De Schryver Thomas , Dierick Manuel , Heyndrickx Marjolein , Van Stappen Jeroen , Boone Marijn A. , Van Hoorebeke Luc , Boone Matthieu N.
Published: May 2018

This work presents a framework to exploit the synergy between Digital Volume Correlation (DVC) and iterative CT reconstruction to enhance the quality of high-resolution dynamic X-ray CT (4D-µCT) and obtain quantitative results from the acquired dataset in the form of 3D strain maps which can be directly correlated to the material properties. Furthermore, we show that the developed framework is capable of strongly reducing motion artifacts even in a dataset containing a single 360° rotation.
Chemical fingerprints of cold physical plasmas – an experimental and computational study using cysteine as tracer compound
Authors: Lackmann J.-W. , Wende K. , Verlackt C. , Golda J. , Volzke J. , Kogelheide F. , Held J. , Bekeschus S. , Bogaerts A. , Schulz-von der Gathen V. , Stapelmann K.
Published: May 2018

Reactive oxygen and nitrogen species released by cold physical plasma are being proposed as effectors in various clinical conditions connected to inflammatory processes. As these plasmas can be tailored in a wide range, models to compare and control their biochemical footprint are desired to infer on the molecular mechanisms underlying the observed effects and to enable the discrimination between different plasma sources. Here, an improved model to trace short-lived reactive species is presented. Using FTIR, high-resolution mass spectrometry, and molecular dynamics computational simulation, covalent modifications of cysteine treated with different plasmas were deciphered and the respective product pattern used to generate a fingerprint of each plasma source. Such, our experimental model allows a fast and reliable grading of the chemical potential of plasmas used for medical purposes. Major reaction products were identified to be cysteine sulfonic acid, cystine, and cysteine fragments. Less-abundant products, such as oxidized cystine derivatives or S-nitrosylated cysteines, were unique to different plasma sources or operating conditions. The data collected point at hydroxyl radicals, atomic O, and singlet oxygen as major contributing species that enable an impact on cellular thiol groups when applying cold plasma in vitro or in vivo.
Morphological and functional changes in the rat retina associated with 2 months of intermittent moderate intraocular pressure elevation
Authors: Tan Bingyao , Gurdita Akshay , Choh Vivian , Joos Karen M. , Prasad Ratna , Bizheva Kostadinka
Published: May 2018

Morphological and functional changes in the rat retina and optic nerve head (ONH), associated with 8 weeks of intermittent moderately elevated intraocular pressure (IOP) were measured with a combined ultrahigh resolution optical coherence tomography (UHR-OCT) and electroretinography (ERG) system. The IOP of male Sprague-Dawley rats was raised in one eye to ~35 mmHg for 1 hour/day on 6 days each week using vascular loops. Single-flash ERG traces and volumetric UHR-OCT images of the ONH were acquired from both eyes before, during and after IOP elevations at weeks 1, 5 and 9 of the study. The UHR-OCT images showed depression of the posterior eye around the ONH during the IOP elevations, the magnitude of which increased significantly from week 1 to week 9 (p = 0.01). The ERG a-wave and b-wave amplitudes increased temporarily during IOP elevations and returned to normal ~30 minutes after loop removal. Recurrent intermittent IOP spikes caused > 30% decrease in the ERG a-wave and b-wave amplitudes measured during the IOP elevations over the course of 2 months. This study suggests that recurrent, relatively short-duration IOP spikes for extended period of time are associated with peri-ONH tissue hypercompliance and reduced retinal functional response to visual stimulation during acute IOP elevation.
A Drosophila Model of Essential Tremor
Authors: Smith Philip , Arias Ronald , Sonti Shilpa , Odgerel Zagaa , Santa-Maria Ismael , McCabe Brian D. , Tsaneva-Atanasova Krasimira , Louis Elan D. , Hodge James J. L. , Clark Lorraine N.
Published: May 2018

Essential Tremor (ET) is one of the most common neurological diseases, with an estimated 7 million affected individuals in the US; the pathophysiology of the disorder is poorly understood. Recently, we identified a mutation (KCNS2 (Kv9.2), c.1137 T > A, p.(D379E) in an electrically silent voltage-gated K+ channel α-subunit, Kv9.2, in a family with ET, that modulates the activity of Kv2 channels. We have produced transgenic Drosophila lines that express either the human wild type Kv9.2 (hKv9.2) or the ET causing mutant Kv9.2 (hKv9.2-D379E) subunit in all neurons. We show that the hKv9.2 subunit modulates activity of endogenous Drosophila K+ channel Shab. The mutant hKv9.2-D379E subunit showed significantly higher levels of Shab inactivation and a higher frequency of spontaneous firing rate consistent with neuronal hyperexcitibility. We also observed behavioral manifestations of nervous system dysfunction including effects on night time activity and sleep. This functional data further supports the pathogenicity of the KCNS2 (p.D379E) mutation, consistent with our prior observations including co-segregation with ET in a family, a likely pathogenic change in the channel pore domain and absence from population databases. The Drosophila hKv9.2 transgenic model recapitulates several features of ET and may be employed to advance our understanding of ET disease pathogenesis.
Long term extension of a randomised controlled trial of probiotics using electronic health records
Authors: Davies Gareth , Jordan Sue , Brooks Caroline J. , Thayer Daniel , Storey Melanie , Morgan Gareth , Allen Stephen , Garaiova Iveta , Plummer Sue , Gravenor Mike
Published: May 2018

Most randomised controlled trials (RCTs) are relatively short term and, due to costs and available resources, have limited opportunity to be re-visited or extended. There is no guarantee that effects of treatments remain unchanged beyond the study. Here, we illustrate the feasibility, benefits and cost-effectiveness of enriching standard trial design with electronic follow up. We completed a 5-year electronic follow up of a RCT investigating the impact of probiotics on asthma and eczema in children born 2005–2007, with traditional fieldwork follow up to two years. Participants and trial outcomes were identified and analysed after five years using secure, routine, anonymised, person-based electronic health service databanks. At two years, we identified 93% of participants and compared fieldwork with electronic health records, highlighting areas of agreement and disagreement. Retention of children from lower socio-economic groups was improved, reducing volunteer bias. At 5 years we identified a reduced 82% of participants. These data allowed the trial’s first robust analysis of asthma endpoints. We found no indication that probiotic supplementation to pregnant mothers and infants protected against asthma or eczema at 5 years. Continued longer-term follow up is technically straightforward.
Magnetic-field induced rotation of magnetosome chains in silicified magnetotactic bacteria
Authors: Blondeau Marine , Guyodo Yohan , Guyot François , Gatel Christophe , Menguy Nicolas , Chebbi Imène , Haye Bernard , Durand-Dubief Mickaël , Alphandery Edouard , Brayner Roberta , Coradin Thibaud
Published: May 2018

Understanding the biological processes enabling magnetotactic bacteria to maintain oriented chains of magnetic iron-bearing nanoparticles called magnetosomes is a major challenge. The study aimed to constrain the role of an external applied magnetic field on the alignment of magnetosome chains inMagnetospirillum magneticumAMB-1 magnetotactic bacteria immobilized within a hydrated silica matrix. A deviation of the chain orientation was evidenced, without significant impact on cell viability, which was preserved after the field was turned-off. Transmission electron microscopy showed that the crystallographic orientation of the nanoparticles within the chains were preserved. Off-axis electron holography evidenced that the change in magnetosome orientation was accompanied by a shift from parallel to anti-parallel interactions between individual nanocrystals. The field-induced destructuration of the chain occurs according to two possible mechanisms: (i) each magnetosome responds individually and reorients in the magnetic field direction and/or (ii) short magnetosome chains deviate in the magnetic field direction. This work enlightens the strong dynamic character of the magnetosome assembly and widens the potentialities of magnetotactic bacteria in bionanotechnology.
A Simple Power Law Governs Many Sensory Amplifications and Multisensory Enhancements
Authors: Billock Vincent A. , Havig Paul R.
Published: May 2018

When one sensory response occurs in the presence of a different sensory stimulation, the sensory response is often amplified. The variety of sensory enhancement data tends to obscure the underlying rules, but it has long been clear that weak signals are usually amplified more than strong ones (the Principle of Inverse Effectiveness). Here we show that for many kinds of sensory amplification, the underlying law is simple and elegant: the amplified response is a power law of the unamplified response, with a compressive exponent that amplifies weak signals more than strong. For both psychophysics and cortical electrophysiology, for both humans and animals, and for both sensory integration and enhancement within a sense, gated power law amplification (amplification of one sense triggered by the presence of a different sensory signal) is often sufficient to explain sensory enhancement.
Turbulence and Cavitation Suppression by Quaternary Ammonium Salt Additives
Authors: Naseri Homa , Trickett Kieran , Mitroglou Nicholas , Karathanassis Ioannis , Koukouvinis Phoevos , Gavaises Manolis , Barbour Robert , Diamond Dale , Rogers Sarah E. , Santini Maurizio , Wang Jin
Published: May 2018

We identify the physical mechanism through which newly developed quaternary ammonium salt (QAS) deposit control additives (DCAs) affect the rheological properties of cavitating turbulent flows, resulting in an increase in the volumetric efficiency of clean injectors fuelled with diesel or biodiesel fuels. Quaternary ammonium surfactants with appropriate counterions can be very effective in reducing the turbulent drag in aqueous solutions, however, less is known about the effect of such surfactants in oil-based solvents or in cavitating flow conditions. Small-angle neutron scattering (SANS) investigations show that in traditional DCA fuel compositions only reverse spherical micelles form, whereas reverse cylindrical micelles are detected by blending the fuel with the QAS additive. Moreover, experiments utilising X-ray micro computed tomography (micro-CT) in nozzle replicas, quantify that in cavitation regions the liquid fraction is increased in the presence of the QAS additive. Furthermore, high-flux X-ray phase contrast imaging (XPCI) measurements identify a flow stabilization effect in the region of vortex cavitation by the QAS additive. The effect of the formation of cylindrical micelles is reproduced with computational fluid dynamics (CFD) simulations by including viscoelastic characteristics for the flow. It is demonstrated that viscoelasticity can reduce turbulence and suppress cavitation, and subsequently increase the injector’s volumetric efficiency.
Organoruthenium(II) Complexes Ameliorates Oxidative Stress and Impedes the Age Associated Deterioration in Caenorhabditis elegans through JNK-1/DAF-16 Signalling
Authors: Devagi G. , Mohankumar A. , Shanmugam G. , Nivitha S. , Dallemer F. , Kalaivani P. , Sundararaj P. , Prabhakaran R.
Published: May 2018

New ruthenium(II) complexes were synthesised and characterized by various spectro analytical techniques. The structure of the complexes 3 and 4 has been confirmed by X-ray crystallography. The complexes were subjected to study their anti-oxidant profile and were exhibited significantly greater in vitro DPPH radical scavenging activity than vitamin C. We found that complexes 1–4 confered tolerance to oxidative stress and extend the mean lifespan of mev-1 mutant worms and wild-type Caenorhabditis elegans. Further, mechanistic study and reporter gene expression analysis revealed that Ru(ƞ6-p-cymene) complexes maintained the intracellular redox status and offers stress resistance through activating JNK-1/DAF-16 signaling axis and possibly by other antioxidant response pathway. Notably, complex 3 and 4 ameliorates the polyQ (a Huntington’s disease associated protein) mediated proteotoxicity and related behavioural deficits in Huntington’s disease models of C. elegans. From these observations, we hope that new Ru(ƞ6-p-cymene) complexes could be further considered as a potential drug to retard aging and age-related neurodegenerative diseases.
Increasing densities of an invasive polychaete enhance bioturbation with variable effects on solute fluxes
Authors: Kauppi L. , Bernard G. , Bastrop R. , Norkko A. , Norkko J.
Published: May 2018

Bioturbation is a key process affecting nutrient cycling in soft sediments. The invasive polychaete genus Marenzelleria spp. has established successfully throughout the Baltic Sea increasing species and functional diversity with possible density-dependent effects on bioturbation and associated solute fluxes. We tested the effects of increasing density of M. arctia, M. viridis and M. neglecta on bioturbation and solute fluxes in a laboratory experiment. Benthic communities in intact sediment cores were manipulated by adding increasing numbers of Marenzelleria spp. The results showed that Marenzelleria spp. in general enhanced all bioturbation metrics, but the effects on solute fluxes varied depending on the solute, on the density and species identity of Marenzelleria, and on the species and functional composition of the surrounding community. M. viridis and M. neglecta were more important in predicting variation in phosphate and silicate fluxes, whereas M. arctia had a larger effect on nitrogen cycling. The complex direct and indirect pathways indicate the importance of considering the whole community and not just species in isolation in the experimental studies. Including these interactions provides a way forward regarding our understanding of the complex ecosystem effects of invasive species.
Metabolomic profile of systemic sclerosis patients
Authors: Murgia Federica , Svegliati Silvia , Poddighe Simone , Lussu Milena , Manzin Aldo , Spadoni Tatiana , Fischetti Colomba , Gabrielli Armando , Atzori Luigi
Published: May 2018

Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls. Moreover, comparing patients affected by limited SSc (lcSSc) and diffuse SSc (dcSSc), 6 discriminant metabolites were identified. The multivariate analysis performed using all the metabolites significantly different revealed glycolysis, gluconeogenesis, energetic pathways, glutamate metabolism, degradation of ketone bodies and pyruvate metabolism as the most important networks. Aspartate, alanine and citrate yielded a high area under receiver-operating characteristic (ROC) curves (AUC of 0.81; CI 0.726–0.93) for discriminating SSc patients from controls, whereas ROC curve generated with acetate, fructose, glutamate, glutamine, glycerol and glutarate (AUC of 0.84; CI 0.7–0.98) discriminated between lcSSc and dcSSc. These results indicated that serum NMR-based metabolomics profiling method is sensitive and specific enough to distinguish SSc from healthy controls and provided a feasible diagnostic tool for the diagnosis and classification of the disease.
Relativistic finite-difference time-domain analysis of high-speed moving metamaterials
Authors: Zhao Yan , Chaimool Sarawuth
Published: May 2018

In this paper, we apply a relativistic finite-difference time-domain (FDTD) method by using the Lorentz transformation to analyze metamaterials moving at a high speed. As an example, we consider a slab of left-handed metmaterial (LHM) with both relative permittivity and permeability equal to −1. Simulation results show that when the LHM slab moves at a high speed, its electromagnetic responses are drastically different from the static case. Specifically, when the LHM slab moves toward the source, for the case of normal incidence, there exists a special velocity at which fields experience a zero spatial phase delay through the LHM slab; while for the oblique incidence, above a certain velocity fields inside the LHM become evanescent. On the other hand, when the LHM slab moves away from the source, for the case of normal incidence, at the same special velocity the magnitudes of both electric and magnetic fields inside the LHM slab reach their minimum values; for the oblique incidence, the slab functions as a field converter. Besides, the transmitted waves through the LHM slab experience a red-shift (to a lower frequency) and the shift is proportional to the velocity of the LHM slab regardless of the moving direction.
FACS-Seq analysis of Pax3-derived cells identifies non-myogenic lineages in the embryonic forelimb
Authors: Singh Arun J. , Chang Chih-Ning , Ma Hsiao-Yen , Ramsey Stephen A. , Filtz Theresa M. , Kioussi Chrissa
Published: May 2018

Skeletal muscle in the forelimb develops during embryonic and fetal development and perinatally. While much is known regarding the molecules involved in forelimb myogenesis, little is known about the specific mechanisms and interactions. Migrating skeletal muscle precursor cells express Pax3 as they migrate into the forelimb from the dermomyotome. To compare gene expression profiles of the same cell population over time, we isolated lineage-tracedPax3+cells (Pax3EGFP) from forelimbs at different embryonic days. We performed whole transcriptome profiling via RNA-Seq ofPax3+cells to construct gene networks involved in different stages of embryonic and fetal development. With this, we identified genes involved in the skeletal, muscular, vascular, nervous and immune systems. Expression of genes related to the immune, skeletal and vascular systems showed prominent increases over time, suggesting a non-skeletal myogenic context ofPax3-derived cells. Using co-expression analysis, we observed an immune-related gene subnetwork active during fetal myogenesis, further implying thatPax3-derived cells are not a strictly myogenic lineage, and are involved in patterning and three-dimensional formation of the forelimb through multiple systems.