bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractReverse 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

AbstractThe 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

AbstractLadakhi 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

AbstractTraumatic 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

AbstractThe 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

AbstractAlthough 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

AbstractTo 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

AbstractHigh-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

AbstractIn-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

AbstractProgress 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

AbstractThe 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

AbstractFeeding 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

AbstractBrassinosteroids (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

AbstractThis 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

AbstractReactive 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.