bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expressed HNSCC variants by HPV-status in a well-characterized Michigan cohort
Authors: Qin Tingting , Zhang Yanxiao , Zarins Katie R. , Jones Tamara R. , Virani Shama , Peterson Lisa A. , McHugh Jonathan B. , Chepeha Douglas , Wolf Gregory T. , Rozek Laura S. , Sartor Maureen A. 
Published: July 2018

AbstractWhile whole-exome DNA sequencing is the most common technology to study genetic variants in tumors in known exonic regions, RNA-seq is cheaper, covers most of the same exonic regions, and is often more readily available. In this study, we show the utility of mRNA-seq-based variant analysis combined with targeted gene sequencing performed on both tumor and matched blood as an alternative when exome data is unavailable. We use the approach to study expressed variant profiles in the well-characterized University of Michigan (UM) head and neck squamous carcinoma (HNSCC) cohort (n = 36). We found that 441 out of 455 (~97%) identified cancer genes with an expressed variant in the UM cohort also harbor a somatic mutation in TCGA. Fourteen (39%) patients had a germline variant in a cancer-related Fanconi Anemia (FA) pathway gene. HPV-positive patients had more nonsynonymous, rare, and damaging (NRD) variants in those genes than HPV-negative patients. Moreover, the known mutational signatures for DNA mismatch repair and APOBEC activation were attributive to the UM expressed NRD variants, and the APOBEC signature contribution differed by HPV status. Our results provide additional support to certain TCGA findings and suggest an association of expressed variants in FA/DNA repair pathways with HPV-associated HNSCC tumorigenesis. These results will benefit future studies on this and other cohorts by providing the genetic variants of key cancer-related genes.
Experimental Demonstration of a Spin Logic Device with Deterministic and Stochastic Mode of Operation
Authors: Debashis Punyashloka , Chen Zhihong 
Published: July 2018

AbstractSpin based logic devices have attracted a lot of research interest due to their potential low-power operation, non-volatility and possibility to enable new computing applications. Here we present an experimental demonstration of a novel spin logic device working at room temperature without the requirement of an external magnetic field. Our device is based on a pair of coupled in-plane magnetic anisotropy (IMA) magnet and a perpendicular magnetic anisotropy (PMA) magnet. The information written in the state of the IMA magnet is transferred to the state of the PMA magnet by means of a symmetry breaking dipolar field, while the two layers are electrically isolated. In addition to having the basic tenets of a logic device, our device has inbuilt memory, taking advantage of the non-volatility of nanomagnets. In another mode of operation, the same device is shown to have the functionality of a true random number generator (TRNG). The combination of logic functionality, nonvolatility and capability to generate true random numbers all in the same spin logic device, makes it uniquely suitable as a hardware for many new computing ideas.
Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps
Authors: Ninomiya Takahiro , Noguchi Emiko , Haruna Takenori , Hasegawa Masayo , Yoshida Takuto , Yamashita Yukiko , Okano Mitsuhiro , Yoshida Naohiro , Haruna Shinichi , Sakuma Yasunori , Ohta Shoichiro , Ono Junya , Izuhara Kenji , Okada Masafumi , Kidoguchi Masanori , Tokunaga Takahiro , Okamoto Masayuki , Kanno Masafumi , Sakashita Masafumi , Takabayashi Tetsuji , Narita Norihiko , Fujieda Shigeharu 
Published: July 2018

AbstractWe previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP.
Altered secretion patterns and cell wall organization caused by loss of PodB function in the filamentous fungus Aspergillus nidulans
Authors: Boppidi Karthik R. , Ribeiro Liliane Fraga Costa , Iambamrung Sirasa , Nelson Sidney M. , Wang Yan , Momany Michelle , Richardson Elizabeth A. , Lincoln Stephen , Srivastava Ranjan , Harris Steven D. , Marten Mark R. 
Published: July 2018

AbstractFilamentous fungi are widely used in the production of a variety of industrially relevant enzymes and proteins as they have the unique ability to secrete tremendous amounts of proteins. However, the secretory pathways in filamentous fungi are not completely understood. Here, we investigated the role of a mutation in the POlarity Defective (podB) gene on growth, protein secretion, and cell wall organization in Aspergillus nidulans using a temperature sensitive (Ts) mutant. At restrictive temperature, the mutation resulted in lack of biomass accumulation, but led to a significant increase in specific protein productivity. Proteomic analysis of the secretome showed that the relative abundance of 584 (out of 747 identified) proteins was altered due to the mutation. Of these, 517 were secreted at higher levels. Other phenotypic differences observed in the mutant include up-regulation of unfolded protein response (UPR), deformation of Golgi apparatus and uneven cell wall thickness. Furthermore, proteomic analysis of cell wall components in the mutant revealed the presence of intracellular proteins in higher abundance accompanied by lower levels of most cell wall proteins. Taken together, results from this study suggest the importance of PodB as a target when engineering fungal strains for enhanced secretion of valuable biomolecules.
Droplet digital PCR shows the D-Loop to be an error prone locus for mitochondrial DNA copy number determination
Authors: Li Brian , Kaushik Sonal , Kalinowski Pola , Kim BaRun , Gershome Cynthia , Ching Joyce , Poburko Damon 
Published: July 2018

AbstractAbsolute quantification of mitochondrial DNA copy number (mCN) provides important insights in many fields of research including cancer, cardiovascular and reproductive health. Droplet digital PCR (ddPCR) natively reports absolute copy number, and we have developed a single-dye, multiplex assay to measure rat mCN that is accurate, precise and affordable. We demonstrate simple methods to optimize this assay and to determine nuclear reference pseudogene copy number to extend the range of mCN that can be measured with this assay. We evaluated two commonly used mitochondrial DNA reference loci to determine mCN, the ND1 gene and the D-Loop. Harnessing the absolute measures of ddPCR, we found that the D-Loop amplifies with a copy number of ~1.0–1.5 relative to other sites on the mitochondrial genome. This anomalous copy number varied significantly between rats and tissues (aorta, brain, heart, liver, soleus muscle). We advocate for avoiding the D-Loop as a mitochondrial reference in future studies of mCN. Further, we report a novel approach to quantifying immunolabelled mitochondrial DNA that provides single-cell estimates of mCN that closely agree with the population analyses by ddPCR. The combination of these assays represents a cost-effective and powerful suite of tools to study mCN.
High-throughput chemical screening to discover new modulators of microRNA expression in living cells by using graphene-based biosensor
Authors: Ryoo Soo-Ryoon , Yim Yeajee , Kim Young-Kwan , Park Il-Soo , Na Hee-Kyung , Lee Jieon , Jang Hongje , Won Cheolhee , Hong Sungwoo , Kim Sung-Yon , Jeon Noo Li , Song Joon Myong , Min Dal-Hee 
Published: July 2018

AbstractMicroRNAs (miRNAs) are important regulatory RNAs that control gene expression in various biological processes. Therefore, control over the disease-related miRNA expression is important both for basic research and for a new class of therapeutic modality to treat serious diseases such as cancer. Here, we present a high-throughput screening strategy to identify small molecules that modulate miRNA expression in living cells. The screen enables simultaneous monitoring of the phenotypic cellular changes associated with the miRNA expression by measuring quantitative fluorescent signals corresponding to target miRNA level in living cells based on a novel biosensor composed of peptide nucleic acid and nano-sized graphene oxide. In this study, the biosensor based cellular screening of 967 compounds (including FDA-approved drugs, enzyme inhibitors, agonists, and antagonists) in cells identified four different classes of small molecules consisting of (i) 70 compounds that suppress both miRNA-21 (miR-21) expression and cell proliferation, (ii) 65 compounds that enhance miR-21 expression and reduce cell proliferation, (iii) 2 compounds that suppress miR-21 expression and increase cell proliferation, and (iv) 21 compounds that enhance both miR-21 expression and cell proliferation. We further investigated the hit compounds to correlate cell morphology changes and cell migration ability with decreased expression of miR-21.
Identification of individual cells from z-stacks of bright-field microscopy images
Authors: Lugagne Jean-Baptiste , Jain Srajan , Ivanovitch Pierre , Ben Meriem Zacchary , Vulin Clément , Fracassi Chiara , Batt Gregory , Hersen Pascal 
Published: July 2018

AbstractObtaining single cell data from time-lapse microscopy images is critical for quantitative biology, but bottlenecks in cell identification and segmentation must be overcome. We propose a novel, versatile method that uses machine learning classifiers to identify cell morphologies fromz-stack bright-field microscopy images. We show that axial information is enough to successfully classify the pixels of an image, without the need to consider in focus morphological features. This fast, robust method can be used to identify different cell morphologies, including the features ofE. coli,S. cerevisiaeand epithelial cells, even in mixed cultures. Our method demonstrates the potential of acquiring and processing Z-stacks for single-layer, single-cell imaging and segmentation.
Arthropod transcriptional activator protein-1 (AP-1) aids tick-rickettsial pathogen survival in the cold
Authors: Khanal Supreet , Taank Vikas , Anderson John F. , Sultana Hameeda , Neelakanta Girish 
Published: July 2018

AbstractIxodes scapularis ticks transmit several pathogens to humans including rickettsial bacterium, Anaplasma phagocytophilum. Here, we report that A. phagocytophilum uses tick transcriptional activator protein-1 (AP-1) as a molecular switch in the regulation of arthropod antifreeze gene, iafgp. RNAi-mediated silencing of ap-1 expression significantly affected iafgp gene expression and A. phagocytophilum burden in ticks upon acquisition from the murine host. Gel shift assays provide evidence that both the bacterium and AP-1 influences iafgp promoter and expression. The luciferase assays revealed that a region of approximately 700 bp upstream of the antifreeze gene is sufficient for AP-1 binding to promote iafgp gene expression. Furthermore, survival assays revealed that AP-1-deficient ticks were more susceptible to cold in comparison to the mock controls. In addition, this study also indicates arthropod AP-1 as a global regulator for some of the tick genes critical for A. phagocytophilum survival in the vector. In summary, our study defines a novel mode of arthropod signaling for the survival of both rickettsial pathogen and its medically important vector in the cold.
Measuring the magnetic axis alignment during solenoids working
Authors: Arpaia Pasquale , Celano Biase , De Vito Luca , Esposito Antonio , Parrella Alessandro , Vannozzi Alessandro 
Published: July 2018

AbstractA method for monitoring the misalignment of the magnetic axis in solenoids is proposed. This method requires only a few measurements of the magnetic field at fixed positions inside the magnet aperture, and thus overcomes the main drawback of sturdy moving mechanics of other Hall sensor-based methods. Conversely to state-of-the-art axis determination, the proposed method can be applied also during magnet operations, when the axis region and almost the whole remaining magnet aperture are not accessible. Moreover, only a few measurements of the magnetic field at fixed positions inside the magnet aperture are required: thus a slow process such as the mapping of the whole aperture of a magnet by means of moving stages is not necessary. The mathematical formulation of the method is explained, and a case study on a model of a multi–layer solenoid is presented. For this case study, the uncertainty is assessed and the optimal placement of the Hall transducers is derived.
Ethylene –dependent and –independent superficial scald resistance mechanisms in ‘Granny Smith’ apple fruit
Authors: Karagiannis Evangelos , Michailidis Michail , Tanou Georgia , Samiotaki Martina , Karamanoli Katerina , Avramidou Evangelia , Ganopoulos Ioannis , Madesis Panagiotis , Molassiotis Athanassios 
Published: July 2018

AbstractSuperficial scald is a major physiological disorder of apple fruit (Malus domestica Borkh.) characterized by skin browning following cold storage; however, knowledge regarding the downstream processes that modulate scald phenomenon is unclear. To gain insight into the mechanisms underlying scald resistance, ‘Granny Smith’ apples after harvest were treated with diphenylamine (DPA) or 1-methylcyclopropene (1-MCP), then cold stored (0 °C for 3 months) and subsequently were ripened at room temperature (20 °C for 8 days). Phenotypic and physiological data indicated that both chemical treatments induced scald resistance while 1-MCP inhibited the ethylene-dependent ripening. A combination of multi-omic analysis in apple skin tissue enabled characterization of potential genes, proteins and metabolites that were regulated by DPA and 1-MCP at pro-symptomatic and scald-symptomatic period. Specifically, we characterized strata of scald resistance responses, among which we focus on selected pathways including dehydroabietic acid biosynthesis and UDP-D-glucose regulation. Through this approach, we revealed scald-associated transcriptional, proteomic and metabolic signatures and identified pathways modulated by the common or distinct functions of DPA and 1-MCP. Also, evidence is presented supporting that cytosine methylation-based epigenetic regulation is involved in scald resistance. Results allow a greater comprehension of the ethylene–dependent and –independent metabolic events controlling scald resistance.
Monitoring and detection of leprosy patients in Southwest China: A retrospective study, 2010–2014
Authors: Le Wang , Haiqin Jiang , Danfeng Hao , Ying Shi , Wenyue Zhang , Jun Yang , Li Xiong , Tiejun Shui , Limei Shen , Jie Liu , De Wang , Yong Ning , Yangying Liu , Hao Wang , Yanfei Kuang , Bin Li , Maeda Yumi , Duthie Malcolm , Meiwen Yu , Hongsheng Wang , Liangbin Yan , Guocheng Zhang , Baoxi Wang , Heng Gu 
Published: July 2018

AbstractMore than 100 counties, mainly in southwest China, report incidence rates of leprosy >1/100,000. The current study analysed the epidemiology of leprosy in southwest China to improve our understanding of the transmission pattern and improve control programs. 207 counties were selected in southwest China. Leprosy patients and their household contacts were recruited. The data from the medical interview and the serological antileprosy antibody of the leprosy patients were analysed. A total of 2,353 new cases of leprosy were interviewed. The distribution of leprosy patients was partly associated with local natural and economic conditions, especially several pocket areas. A total of 53 from 6643 household contacts developed leprosy, and the incidence rate of leprosy in the household contacts was 364/100,000 person-years. We found that NDO-BSA attained higher positive rates than MMP-II and LID-1 regardless of clinical types, disability and infection time in leprosy patients. By means of combination of antigens, 88.4% patients of multibacillary leprosy were detected, in contrast to 59.9% in paucibacillary leprosy. Household contacts should be given close attention for the early diagnosis, disruption of disease transmission and precise control. Applications of serology for multi-antigens were recommended for effective coverage and monitoring in leprosy control.
A network pharmacology-based approach to analyse potential targets of traditional herbal formulas: An example of Yu Ping Feng decoction
Authors: Zuo Huali , Zhang Qianru , Su Shibing , Chen Qilong , Yang Fengqing , Hu Yuanjia 
Published: July 2018

AbstractHerbal formulas from traditional Chinese medicines (TCMs) have been extensively used in clinics as effective therapies, but it is still a great challenge to demonstrate the scientific basis for their therapeutic effects at the level of molecular biology. By taking a classic herbal formula (Yu Ping Feng decoction, YPF) as an example, this study developed a novel network pharmacology based method to identify its potential therapeutic targets. First, this study constructed a “targets–(pathways)–targets” (TPT) network in which targets of YPF were connected by relevant pathways; then, this network was decomposed into separate modules with strong internal connections; lastly, the propensity of each module toward different diseases was assessed by a contribution score. On the basis of a significant association between network modules and therapeutic diseases validated by chi-square test (p-value < 0.001), this study identified the network module with the strongest propensity toward therapeutic diseases of YPF. Further, the targets with the highest centrality in this module are recommended as YPF’s potential therapeutic targets. By integrating the complicated “multi-targets–multi-pathways–multi-diseases” relationship of herbal formulas, the method shows promise for identifying its potential therapeutic targets, which could contribute to the modern scientific illustration of TCMs’ traditional clinical applications.
Both gravistimulation onset and removal trigger an increase of cytoplasmic free calcium in statocytes of roots grown in microgravity
Authors: Bizet François , Pereda-Loth Veronica , Chauvet Hugo , Gérard Joëlle , Eche Brigitte , Girousse Christine , Courtade Monique , Perbal Gérald , Legué Valérie 
Published: July 2018

AbstractGravity is a permanent environmental signal guiding plant growth and development. Gravity sensing in plants starts with the displacement of starch-filled plastids called statoliths, ultimately leading to auxin redistribution and organ curvature. While the involvement in gravity sensing of several actors such as calcium is known, the effect of statolith displacement on calcium changes remains enigmatic. Microgravity is a unique environmental condition offering the opportunity to decipher this link. In this study, roots of Brassica napus were grown aboard the International Space Station (ISS) either in microgravity or in a centrifuge simulating Earth gravity. The impact of short simulated gravity onset and removal was measured on statolith positioning and intracellular free calcium was assessed using pyroantimonate precipitates as cytosolic calcium markers. Our findings show that a ten-minute onset or removal of gravity induces very low statolith displacement, but which is, nevertheless, associated with an increase of the number of pyroantimonate precipitates. These results highlight that a change in the cytosolic calcium distribution is triggered in absence of a significant statolith displacement.
Nasal microbiota clusters associate with inflammatory response, viral load, and symptom severity in experimental rhinovirus challenge
Authors: Lehtinen Markus J. , Hibberd Ashley A. , Männikkö Sofia , Yeung Nicolas , Kauko Tommi , Forssten Sofia , Lehtoranta Liisa , Lahtinen Sampo J. , Stahl Buffy , Lyra Anna , Turner Ronald B. 
Published: July 2018

AbstractThe role of nasal and fecal microbiota in viral respiratory infections has not been established. We collected nasal swabs and washes, and fecal samples in a clinical study assessing the effect of probiotic Bifidobacterium animalis subsp. lactis Bl-04 on experimental rhinovirus infection. The nasal and fecal microbiota were characterized by 16S rRNA gene sequencing. The resulting data were compared with nasal inflammatory marker concentrations, viral load, and clinical symptoms. By using unsupervised clustering, the nasal microbiota divided into six clusters. The clusters predominant of Staphylococcus, Corynebacterium/Alloiococcus, Moraxella, and Pseudomonadaceae/Mixed had characteristic inflammatory marker and viral load profiles in nasal washes. The nasal microbiota clusters of subjects before the infection associated with the severity of clinical cold symptoms during rhinovirus infection. Rhinovirus infection and probiotic intervention did not significantly alter the composition of nasal or fecal microbiota. Our results suggest that nasal microbiota may influence the virus load, host innate immune response, and clinical symptoms during rhinovirus infection, however, further studies are needed.
The actin capping protein in Aspergillus nidulans enhances dynein function without significantly affecting Arp1 filament assembly
Authors: Zhang Jun , Qiu Rongde , Xiang Xin 
Published: July 2018

AbstractThe minus-end-directed microtubule motor cytoplasmic dynein requires the dynactin complex for in vivo functions. The backbone of the vertebrate dynactin complex is the Arp1 (actin-related protein 1) mini-filament whose barbed end binds to the heterodimeric actin capping protein. However, it is unclear whether the capping protein is a dynactin component in lower eukaryotic organisms, especially because it does not appear to be a component of the budding yeast dynactin complex. Here our biochemical data show that the capping protein is a component of the dynactin complex in the filamentous fungus Aspergillus nidulans. Moreover, deletion of the gene encoding capping protein alpha (capA) results in a defect in both nuclear distribution and early-endosome transport, two dynein-mediated processes. However, the defect in either process is less severe than that exhibited by a dynein heavy chain mutant or the ∆p25 mutant of dynactin. In addition, loss of capping protein does not significantly affect the assembly of the dynactin Arp1 filament or the formation of the dynein-dynactin-∆C-HookA (Hook in A. nidulans) complex. These results suggest that fungal capping protein is not important for Arp1 filament assembly but its presence is required for enhancing dynein function in vivo.