bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease
Authors: Batta Gyula , Soltész Lilla , Kovács Tamás , Bozó Tamás , Mészár Zoltán , Kellermayer Miklós , Szöllősi János , Nagy Peter 
Published: January 2018

AbstractGaucher disease is a lysosomal storage disease characterized by the malfunction of glucocerebrosidase resulting in the accumulation of glucosylceramide and other sphingolipids in certain cells. Although the disease symptoms are usually attributed to the storage of undigested substrate in lysosomes, here we show that glycosphingolipids accumulating in the plasma membrane cause profound changes in the properties of the membrane. The fluidity of the sphingolipid-enriched membrane decreased accompanied by the enlargement of raft-like ordered membrane domains. The mobility of non-raft proteins and lipids was severely restricted, while raft-resident components were only mildly affected. The rate of endocytosis of transferrin receptor, a non-raft protein, was significantly retarded in Gaucher cells, while the endocytosis of the raft-associated GM1 ganglioside was unaffected. Interferon-γ-induced STAT1 phosphorylation was also significantly inhibited in Gaucher cells. Atomic force microscopy revealed that sphingolipid accumulation was associated with a more compliant membrane capable of producing an increased number of nanotubes. The results imply that glycosphingolipid accumulation in the plasma membrane has significant effects on membrane properties, which may be important in the pathogenesis of Gaucher disease.
Bacterial community assembly from cow teat skin to ripened cheeses is influenced by grazing systems
Authors: Frétin Marie , Martin Bruno , Rifa Etienne , Isabelle Verdier-Metz , Pomiès Dominique , Ferlay Anne , Montel Marie-Christine , Delbès Céline 
Published: January 2018

AbstractThe objectives of this study were to explore bacterial community assembly from cow teat skin to raw milk cheeses and to evaluate the role of farming systems on this assembly using 16S rRNA gene high-throughput sequencing. The two grazing systems studied (extensive vs. semi-extensive) had a greater effect on the microbiota of cow teat skin than on that of raw milks and cheeses. On teat skin, the relative abundance of several taxa at different taxonomic levels (Coriobacteriia, Bifidobacteriales, Corynebacteriales, Lachnospiraceae, Atopobium, and Clostridium) varied depending on the grazing system and the period (early or late summer). In cheese, the abundance of sub-dominant lactic acid bacteria (LAB) varied depending on the grazing system. Overall, 85% of OTUs detected in raw milks and 27% of OTUs detected in ripened cheeses were also found on cow teat skin. Several shared OTUs were assigned to taxa known to be involved in the development of cheese sensory characteristics, such as Micrococcales, Staphylococcaceae, and LAB. Our results highlight the key role of cow teat skin as a reservoir of microbial diversity for raw milk, and for the first time, that cow teat skin serves as a potential source of microorganisms found in raw-milk cheeses.
Comparative Analysis of Gene Expression Profiles of Human Dental Fluorosis and Kashin-Beck Disease
Authors: Zhang Qiang , Ma Jing , Liu Haiqing , He Duolong , Chen Lilin , Wu Haikun , Jiang Hong , Lu Qing , Bai Shenglu 
Published: January 2018

AbstractTo explore the pathologies of Kashin-Beck disease (KBD) and KBD accompanied with dental fluorosis (DF), we conducted a comparative analysis of gene expression profiles. 12 subjects were recruited, including 4 KBD patients, 4 patients with KBD and DF and 4 healthy subjects. Genome-wide expression profiles from their peripheral blood mononuclear cells were evaluated by customized oligonucleotide microarray. R programming software was used for the microarray data analysis followed by functional enrichment analysis through KOBAS. Several potential biomarkers were identified, and quantitative real-time reverse transcription–polymerase chain reaction (qRT-PCR) was used for their validation. In this study, 28 genes and 8 genes were found to be up- and down-regulated respectively in KBD patients compared with health subjects. In patients with KBD and DF, we obtained 10 up-regulated and 3 down-regulated genes compared with health controls. Strikingly, no differential expression gene (DEG) was identified between the two groups of patients. A total of 10 overlaps (DUSP2, KLRF1, SRP19, KLRC3, CD69, SIK1, ITGA4, ID3, HSPA1A, GPR18) were obtained between DEGs of patients with KBD and patients with KBD and DF. They play important roles in metabolism, differentiation, apoptosis and bone-development. The relative abundance of 8 DEGs, i.e. FCRL6, KLRC3, CXCR4, CD93, CLK1, GPR18, SRP19 and KLRF1, were further confirmed by qRT-PCR analysis.
Surveillance of vector-borne pathogens under imperfect detection: lessons from Chagas disease risk (mis)measurement
Authors: Minuzzi-Souza Thaís Tâmara Castro , Nitz Nadjar , Cuba César Augusto Cuba , Hagström Luciana , Hecht Mariana Machado , Santana Camila , Ribeiro Marcelle , Vital Tamires Emanuele , Santalucia Marcelo , Knox Monique , Obara Marcos Takashi , Abad-Franch Fernando , Gurgel-Gonçalves Rodrigo 
Published: January 2018

AbstractVector-borne pathogens threaten human health worldwide. Despite their critical role in disease prevention, routine surveillance systems often rely on low-complexity pathogen detection tests of uncertain accuracy. In Chagas disease surveillance, optical microscopy (OM) is routinely used for detecting Trypanosoma cruzi in its vectors. Here, we use replicate T. cruzi detection data and hierarchical site-occupancy models to assess the reliability of OM-based T. cruzi surveillance while explicitly accounting for false-negative and false-positive results. We investigated 841 triatomines with OM slides (1194 fresh, 1192 Giemsa-stained) plus conventional (cPCR, 841 assays) and quantitative PCR (qPCR, 1682 assays). Detections were considered unambiguous only when parasitologists unmistakably identified T. cruzi in Giemsa-stained slides. qPCR was >99% sensitive and specific, whereas cPCR was ~100% specific but only ~55% sensitive. In routine surveillance, examination of a single OM slide per vector missed ~50–75% of infections and wrongly scored as infected ~7% of the bugs. qPCR-based and model-based infection frequency estimates were nearly three times higher, on average, than OM-based indices. We conclude that the risk of vector-borne Chagas disease may be substantially higher than routine surveillance data suggest. The hierarchical modelling approach we illustrate can help enhance vector-borne disease surveillance systems when pathogen detection is imperfect.
Inflammatory Proteomic Network Analysis of Statin-treated and Lipopolysaccharide-activated Macrophages
Authors: Kamal Abu Hena M. , Chakrabarty Jayanta K. , Udden S. M. Nashir , Zaki Md. Hasan , Chowdhury Saiful M. 
Published: January 2018

AbstractA significant component of immune biology research is the investigation of protein encoding genes that play central roles in contributing inflammatory response. A gel-free quantitative bottom-up proteomics study was performed on immune cell macrophages after the combined treatment of lipopolysaccharide (LPS) and statin drugs using mass spectrometry and a detailed bioinformatics analyses were conducted. Systematic bioinformatics analysis was applied for discovering novel relationships among proteins and effects of statin and lipopolysaccharide in macrophage cells. Based on gene ontology, majority of protein encoding genes was involved in metabolic and cellular processes and are actively associated with binding, structural molecular, and catalytic activity. Notably, proteomic data analyzed by Ingenuity Pathway Analysis (IPA), discovered the plectin and prohibitin 2 protein interactions network and inflammatory-disease based protein networks. Two up-regulated proteins, plectin and prohibitin 2, were further validated by immunoblotting. Plectin was also cross-validated by immunocytochemistry, since its expression was highly modulated by statin but inhibited during LPS-stimulation. Collectively, the significant up-regulation of plectin due to the treatment of statin, suggests that statin has a significant impact on the cytoskeletal networks of cells. Plectin might have a significant role in the intermediate filament assembly and dynamics, and possibly stabilizing and crosslinking intermediate filament networks.
Comparison of changes in mitochondrial bioenergetics between keratinocytes in human external auditory canal skin and cholesteatomas from normoxia to hypoxia
Authors: Shih Cheng-Ping , Lee Jen-Tin , Chen Hang-Kang , Lin Yi-Chun , Chen Hsin-Chien , Lin Yuan-Yung , Kuo Chao-Yin , Chen Yu-Ting , Wang Chih-Hung 
Published: January 2018

AbstractCholesteatoma has attracted many studies seeking to uncover its nature and the pathogenesis of related diseases. However, no researchers have explored the mitochondrial bioenergetics of cholesteatoma. The aim of this study was to investigate the energy demand and differential mitochondrial respiration profiles between keratinocytes in external auditory canal (EAC) skin and cholesteatoma samples cultured in normoxic (20% O2) and hypoxic (5% O2) conditions. Enhanced cellular proliferation of both types of keratinocytes was found in hypoxia compared to normoxia. In 20% O2conditions, cholesteatoma keratinocytes exhibited less mitochondrial mass, lower ATP levels, and significantly lower basal oxygen consumption rate (OCR) and reserve capacity compared to normal skin keratinocytes. In contrast, in hypoxic conditions, cholesteatoma keratinocytes showed markedly higher levels in maximal OCR and reserve capacity, as well as lower proton leak OCRs, compared to normal skin keratinocytes. Hypoxia induced the reverse mitochondrial bioenergy profile from that in normoxia between these two types of keratinocytes, implying that an adaptive change of mitochondrial respiration to oxygen fluctuations may develop in cases of cholesteatoma. Such adaptation in response to hypoxic conditions may play a role in explaining the pathogenesis of acquired cholesteatoma.
Modeling tumor immunity of mouse glioblastoma by exhausted CD8+ T cells
Authors: Nakashima Hiroshi , Alayo Quazim A. , Penaloza-MacMaster Pablo , Freeman Gordon J. , Kuchroo Vijay K. , Reardon David A. , Fernandez Soledad , Caligiuri Michael , Chiocca E. Antonio 
Published: January 2018

AbstractT cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses. We developed a novel mouse glioma model expressing a viral epitope derived from lymphocytic choriomeningitis virus (LCMV), which allowed monitoring of tumor-specific CD8 T-cell responses. These CD8 T cells express high levels of PD-1 and are unable to reject tumors, but this can be reversed by anti-PD-1 treatment. These results suggest the efficacy of PD-1 blockade as a treatment for glioblastoma, an aggressive tumor that results in a uniformly lethal outcome. Importantly, this new syngeneic tumor model may also provide further opportunities to characterize anti-tumor T cell exhaustion and develop novel cancer immunotherapies.
Protein tyrosine kinase, PtkA, is required for Mycobacterium tuberculosis growth in macrophages
Authors: Wong Dennis , Li Wu , Chao Joseph D. , Zhou Peifu , Narula Gagandeep , Tsui Clement , Ko Mary , Xie Jianping , Martinez-Frailes Carlos , Av-Gay Yossef 
Published: January 2018

AbstractProtein phosphorylation plays a key role in Mycobacterium tuberculosis (Mtb) physiology and pathogenesis. We have previously shown that a secreted protein tyrosine phosphatase, PtpA, is essential for Mtb inhibition of host macrophage acidification and maturation, and is a substrate of the protein tyrosine kinase, PtkA, encoded in the same operon. In this study, we constructed a ∆ptkA deletion mutant in Mtb and found that the mutant exhibited impaired intracellular survival in the THP-1 macrophage infection model, correlated with the strain’s inability to inhibit macrophage phagosome acidification. By contrast, the mutant displayed increased resistance to oxidative stress in vitro. Proteomic and transcriptional analyses revealed upregulation of ptpA, and increased secretion of TrxB2, in the ΔptkA mutant. Kinase and protein-protein interaction studies demonstrated that TrxB2 is a substrate of PtkA phosphorylation. Taken together these studies establish a central role for the ptkA-ptpA operon in Mtb pathogenesis.
Zircon evidence for incorporation of terrigenous sediments into the magma source of continental basalts
Authors: Xu Zheng , Zheng Yong-Fei , Zhao Zi-Fu 
Published: January 2018

AbstractCrustal components may be incorporated into continental basalts by either shallow contamination or deep mixing. While the former proceeds at crustal depths with common preservation of refractory minerals, the latter occurs at mantle depths with rare survival of relict minerals. Discrimination between the two mechanisms has great bearing to subcontinental mantle geochemistry. Here we report the occurrence of relict zircons in Cenozoic continental basalts from eastern China. A combined study of zircon U-Pb ages and geochemistry indicates that detrital zircons were carried by terrigenous sediments into a subcontinental subduction zone, where the zircon were transferred by fluids into the magma sources of continental basalts. The basalts were sampled from three petrotectonic units with distinct differences in their magmatic and metamorphic ages, making the crustal contamination discernible. The terrigenous sediments were carried by the subducting oceanic crust into the asthenospheric mantle, producing both soluble and insoluble materials at the slab-mantle interface. These materials were served as metasomatic agents to react with the overlying mantle wedge peridotite, generating a kind of ultramafic metasomatites that contain the relict zircons. Therefore, the occurrence of relict zircons in continental basalts indicates that this refractory mineral can survive extreme temperature-pressure conditions in the asthenospheric mantle.
Controlled Alternate Quantum Walks based Quantum Hash Function
Authors: Li Dan , Yang Yu-Guang , Bi Jing-Lin , Yuan Jia-Bin , Xu Juan 
Published: January 2018

AbstractThrough introducing controlled alternate quantum walks, we present controlled alternate quantum walks (CAQW) based quantum hash function. CAQW based quantum hash function have excellent security, outstanding statistical performance and splendid expansibility. Furthermore, due to the structure of alternate quantum walks, implementing CAQW based quantum hash function significantly reduces the resources necessary for its feasible experimental realization than implementing other quantum hash functions.
HybTrack: A hybrid single particle tracking software using manual and automatic detection of dim signals
Authors: Lee Byung Hun , Park Hye Yoon 
Published: January 2018

AbstractSingle particle tracking is a compelling technique for investigating the dynamics of nanoparticles and biological molecules in a broad range of research fields. In particular, recent advances in fluorescence microscopy have made single molecule tracking a prevalent method for studying biomolecules with a high spatial and temporal precision. Particle tracking algorithms have matured over the past three decades into more easily accessible platforms. However, there is an inherent difficulty in tracing particles that have a low signal-to-noise ratio and/or heterogeneous subpopulations. Here, we present a new MATLAB based tracking program which combines the benefits of manual and automatic tracking methods. The program prompts the user to manually locate a particle when an ambiguous situation occurs during automatic tracking. We demonstrate the utility of this program by tracking the movement of β-actin mRNA in the dendrites of cultured hippocampal neurons. We show that the diffusion coefficient of β-actin mRNA decreases upon neuronal stimulation by bicuculline treatment. This tracking method enables an efficient dissection of the dynamic regulation of biological molecules in highly complex intracellular environments.
Ultrafast syn-eruptive degassing and ascent trigger high-energy basic eruptions
Authors: Giuffrida Marisa , Viccaro Marco , Ottolini Luisa 
Published: January 2018

AbstractLithium gradients in plagioclase are capable of recording extremely short-lived processes associated with gas loss from magmas prior to extrusion at the surface. We present SIMS profiles of the 7Li/30Si ion ratio in plagioclase crystals from products of the paroxysmal sequence that occurred in the period 2011–2013 at Mt. Etna (Italy) in an attempt to constrain the final ascent and degassing processes leading to these powerful eruptions involving basic magma. The observed Li concentrations reflect cycles of Li addition to the melt through gas flushing, and a syn-eruptive stage of magma degassing driven by decompression that finally produce significant Li depletion from the melt. Modeling the decreases in Li concentration in plagioclase by diffusion allowed determination of magma ascent timescales that are on the order of minutes or less. Knowledge of the storage depth beneath the volcano has led to the quantification of a mean magma ascent velocity of ~43 m/s for paroxysmal eruptions at Etna. The importance of these results relies on the application of methods, recently used exclusively for closed-system volcanoes producing violent eruptions, to open-conduit systems that have generally quiet eruptive periods of activity sometimes interrupted by sudden re-awakening and the production of anomalously energetic eruptions.
Increased Abundance of Clostridium and Fusobacterium in Gastric Microbiota of Patients with Gastric Cancer in Taiwan
Authors: Hsieh Yung-Yu , Tung Shui-Yi , Pan Hung-Yu , Yen Chih-Wei , Xu Huang-Wei , Lin Ying-Jhen , Deng Yi-Fang , Hsu Wan-Ting , Wu Cheng-Shyong , Li Chin 
Published: January 2018

AbstractHelicobacter pylori is recognised as a main risk factor for gastric cancer. However, approximately half of the patients with gastritis are negative for H. pylori infection, and the abundance of H. pylori decreases in patients with cancer. In the current study, we profiled gastric epithelium-associated bacterial species in patients with gastritis, intestinal metaplasia, and gastric cancer to identify additional potential pathogenic bacteria. The overall composition of the microbiota was similar between the patients with gastritis and those with intestinal metaplasia. H. pylori was present in half of the non-cancer group, and the dominant bacterial species in the H. pylori-negative patients were Burkholderia, Enterobacter, and Leclercia. The abundance of those bacteria was similar between the cancer and non-cancer groups, whereas the frequency and abundance of H. pylori were significantly lower in the cancer group. Instead, Clostridium, Fusobacterium, and Lactobacillus species were frequently abundant in patients with gastric cancer, demonstrating a gastric cancer-specific bacterial signature. A receiver operating characteristic curve analysis showed that Clostridium colicanis and Fusobacterium nucleatum exhibited a diagnostic ability for gastric cancer. Our findings indicate that the gastric microenvironment is frequently colonised by Clostridium and Fusobacterium in patients with gastric cancer.
Genome-wide comparisons reveal evidence for a species complex in the black-lip pearl oyster Pinctada margaritifera (Bivalvia: Pteriidae)
Authors: Lal Monal M. , Southgate Paul C. , Jerry Dean R. , Zenger Kyall R. 
Published: January 2018

AbstractEvolutionary relationships in the black-lip pearl oyster Pinctada margaritifera which is highly valued for pearl production remain poorly understood. This species possesses an 18,000 km Indo-Pacific natural distribution, and its current description includes six subspecies defined exclusively on morphological characters. To evaluate its taxonomic identity using molecular data, 14 populations in both the Indian and Pacific Oceans (n = 69), and the congeneric taxa P. maxima and P. mazatlanica (n = 29 and n = 10, respectively) were sampled. Phylogenomic reconstruction was carried out using both 8,308 genome-wide SNPs and 10,000 dominant loci (DArTseq PAVs). Reconstructions using neighbour-joining (Nei’s 1972 distances), maximum likelihood and Bayesian approaches all indicate that the taxonomy of P. margaritifera is quite complex, with distinct evolutionary significant units (ESUs) identified within Tanzanian and Iranian populations. Contrastingly, phylogenies generated for Pacific Ocean oysters resolved a large monophyletic clade, suggesting little support for two current morphological subspecies classifications. Furthermore, P. mazatlanica formed a basal clade closest to French Polynesian P. margaritifera, suggesting it may be conspecific. Collectively, these findings provide evidence that P. margaritifera comprises a species complex, perhaps as a result of population fragmentation and increased divergence at range limits.
Development and characterization of a novel luciferase based cytotoxicity assay
Authors: Matta Hittu , Gopalakrishnan Ramakrishnan , Choi Sunju , Prakash Rekha , Natarajan Venkatesh , Prins Ruben , Gong Songjie , Chitnis Saurabh D. , Kahn Michael , Han Xu , Chaudhary Vishan , Soni Adam , Sernas Jennifer , Khan Prottasha , Wang Dan , Chaudhary Preet M. 
Published: January 2018

AbstractA simple, accurate, sensitive and robust assay that can rapidly and specifically measure the death of target cells would have applications in many areas of biomedicine and particularly for the development of novel cellular- and immune-therapeutics. In this study, we describe a novel cytotoxicity assay, termed the Matador assay, which takes advantage of the extreme brightness, stability and glow-like characteristics of recently discovered novel marine luciferases and their engineered derivatives. The assay involves expression of a luciferase of interest in target cells in a manner so that it is preferentially retained within the healthy cells but is either released from dead and dying cells or whose activity can be preferentially measured in dead and dying cells. We demonstrate that this assay is highly sensitive, specific, rapid, and can be performed in a single-step manner without the need for any expensive equipment. We further validate this assay by demonstrating its ability to detect cytotoxicity induced by several cellular and immune-therapeutic agents including antibodies, natural killer cells, chimeric antigen receptor expressing T cells and a bispecific T cell engager.