bluuebunny/crossref_metadata_2025_split huggingface dataset:
The secondary resistome of multidrug-resistant Klebsiella pneumoniae
Authors: Jana Bimal , Cain Amy K. , Doerrler William T. , Boinett Christine J. , Fookes Maria C. , Parkhill Julian , Guardabassi Luca 
Published: February 2017

AbstractKlebsiella pneumoniae causes severe lung and bloodstream infections that are difficult to treat due to multidrug resistance. We hypothesized that antimicrobial resistance can be reversed by targeting chromosomal non-essential genes that are not responsible for acquired resistance but essential for resistant bacteria under therapeutic concentrations of antimicrobials. Conditional essentiality of individual genes to antimicrobial resistance was evaluated in an epidemic multidrug-resistant clone of K. pneumoniae (ST258). We constructed a high-density transposon mutant library of >430,000 unique Tn5 insertions and measured mutant depletion upon exposure to three clinically relevant antimicrobials (colistin, imipenem or ciprofloxacin) by Transposon Directed Insertion-site Sequencing (TraDIS). Using this high-throughput approach, we defined three sets of chromosomal non-essential genes essential for growth during exposure to colistin (n = 35), imipenem (n = 1) or ciprofloxacin (n = 1) in addition to known resistance determinants, collectively termed the “secondary resistome”. As proof of principle, we demonstrated that inactivation of a non-essential gene not previously found linked to colistin resistance (dedA) restored colistin susceptibility by reducing the minimum inhibitory concentration from 8 to 0.5 μg/ml, 4-fold below the susceptibility breakpoint (S ≤ 2 μg/ml). This finding suggests that the secondary resistome is a potential target for developing antimicrobial “helper” drugs that restore the efficacy of existing antimicrobials.
High FMNL3 expression promotes nasopharyngeal carcinoma cell metastasis: role in TGF-β1-induced epithelia-to-mesenchymal transition
Authors: Wu Yanxia , Shen Zhihua , Wang Keke , Ha Yanping , Lei Hong , Jia Yanan , Ding Ranran , Wu Dongmei , Gan Siyuan , Li Rujia , Luo Botao , Jiang Hanguo , Jie Wei 
Published: February 2017

AbstractFormin-like 3 (FMNL3) plays a crucial role in cytoskeletal mediation and is potentially a biomarker for cell migration; however, its role in cancer metastasis remains unknown. In this study, we found elevated FMNL3 protein expression in clinical nasopharyngeal carcinoma (NPC) tissues. FMNL3 expression positively correlated to the clinical stage, T (tumour), N (lymph node metastasis) and M (distant metastasis) classification of NPC patients. Moreover, FMNL3 positively correlated to Vimentin expression and negatively correlated to E-cadherin expression in clinical NPC samples. In vitro experiments showed that FMNL3 expression was inversely related to NPC cell differentiation status. Overexpression of FMNL3 led to epithelial-to-mesenchymal transition (EMT) in well differentiated CNE1 cells. TGF-β1-treated poorly differentiated CNE2 cells showed changes in EMT accompanied by enhanced FMNL3 expression and cell migration. On the contrary, knockdown of FMNL3 partially attenuated the TGF-β1-promoted CNE2 cell migration, together with associated changes in EMT markers. Finally, knockdown of FMNL3 also weakened EMT in tumours in xenographs. Our study indicates for the first time that TGF-β1/FMNL3 signalling may be a novel mechanism mediating EMT in NPC, which is closely associated with NPC metastasis.
Dual Electrophoresis Detection System for Rapid and Sensitive Immunoassays with Nanoparticle Signal Amplification
Authors: Zhang Fangfang , Ma Junjie , Watanabe Junji , Tang Jinlong , Liu Huiyu , Shen Heyun 
Published: February 2017

AbstractAn electrophoretic technique was combined with an enzyme-linked immunosorbent assay (ELISA) system to achieve a rapid and sensitive immunoassay. A cellulose acetate filter modified with polyelectrolyte multilayer (PEM) was used as a solid substrate for three-dimensional antigen-antibody reactions. A dual electrophoresis process was used to induce directional migration and local condensation of antigens and antibodies at the solid substrate, avoiding the long diffusion times associated with antigen-antibody reactions in conventional ELISAs. The electrophoretic forces drove two steps in the ELISA process, namely the adsorption of antigen, and secondary antibody-labelled polystyrene nanoparticles (NP-Ab). The total time needed for dual electrophoresis-driven detection was just 4 min, nearly 2 h faster than a conventional ELISA system. Moreover, the rapid NP-Ab electrophoresis system simultaneously achieved amplification of the specific signal and a reduction in noise, leading to a more sensitive NP-Ab immunoassay with a limit of detection (LOD) of 130 fM, and wide range of detectable concentrations from 0.13 to 130 pM. These results suggest that the combination of dual electrophoresis detection and NP-Ab signal amplification has great potential for future immunoassay systems.
Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma
Authors: Lenka Govinda , Tsai Mong-Hsun , Lin Hsin-Chieh , Hsiao Jen-Hao , Lee Yi-Ching , Lu Tzu-Pin , Lee Jang-Ming , Hsu Chung-Ping , Lai Liang-Chuan , Chuang Eric Y. 
Published: February 2017

AbstractDNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r ≤ −0.5), corresponding to 17 genes. Examining the endogenous expression in lung cancer cell lines, five of the genes were found to be significantly down-regulated. Furthermore, in tumor cells alone, 5-aza-2′-deoxycytidine treatment increased the expression levels of STXBP6 in a dose dependent manner and pyrosequencing showed higher percentage of methylation in STXBP6 promoter. Functional analysis revealed that overexpressed STXBP6 in A549 and H1299 cells significantly decreased cell proliferation, colony formation, and migration, and increased apoptosis. Finally, significantly lower survival rates (P < 0.05) were observed when expression levels of STXBP6 were low. Our results provide a basis for the genetic etiology of lung adenocarcinoma by demonstrating the possible role of hypermethylation of STXBP6 in poor clinical outcomes in lung cancer patients.
Cystinosis (ctns) zebrafish mutant shows pronephric glomerular and tubular dysfunction
Authors: Elmonem Mohamed A. , Khalil Ramzi , Khodaparast Ladan , Khodaparast Laleh , Arcolino Fanny O. , Morgan Joseph , Pastore Anna , Tylzanowski Przemko , Ny Annelii , Lowe Martin , de Witte Peter A. , Baelde Hans J. , van den Heuvel Lambertus P. , Levtchenko Elena 
Published: February 2017

AbstractThe human ubiquitous protein cystinosin is responsible for transporting the disulphide amino acid cystine from the lysosomal compartment into the cytosol. In humans, Pathogenic mutations of CTNS lead to defective cystinosin function, intralysosomal cystine accumulation and the development of cystinosis. Kidneys are initially affected with generalized proximal tubular dysfunction (renal Fanconi syndrome), then the disease rapidly affects glomeruli and progresses towards end stage renal failure and multiple organ dysfunction. Animal models of cystinosis are limited, with only a Ctns knockout mouse reported, showing cystine accumulation and late signs of tubular dysfunction but lacking the glomerular phenotype. We established and characterized a mutant zebrafish model with a homozygous nonsense mutation (c.706 C > T; p.Q236X) in exon 8 of ctns. Cystinotic mutant larvae showed cystine accumulation, delayed development, and signs of pronephric glomerular and tubular dysfunction mimicking the early phenotype of human cystinotic patients. Furthermore, cystinotic larvae showed a significantly increased rate of apoptosis that could be ameliorated with cysteamine, the human cystine depleting therapy. Our data demonstrate that, ctns gene is essential for zebrafish pronephric podocyte and proximal tubular function and that the ctns-mutant can be used for studying the disease pathogenic mechanisms and for testing novel therapies for cystinosis.
TaWRKY70 transcription factor in wheat QTL-2DL regulates downstream metabolite biosynthetic genes to resist Fusarium graminearum infection spread within spike
Authors: Kage Udaykumar , Yogendra Kalenahalli N. , Kushalappa Ajjamada C. 
Published: February 2017

AbstractA semi-comprehensive metabolomics was used to identify the candidate metabolites and genes to decipher mechanisms of resistance in wheat near-isogenic lines (NILs) containingQTL-2DLagainstFusarium graminearum (Fg). Metabolites, with high fold-change in abundance, belonging tohydroxycinnamic acid amides (HCAAs): such as coumaroylagmatine, coumaroylputrescine andFatty acids: phosphatidic acids (PAs) were identified as resistance related induced (RRI) metabolites in rachis of resistant NIL (NIL-R), inoculated withFg.A WRKY like transcription factor (TF) was identified within theQTL-2DLregion, along with three resistance genes that biosynthesized RRI metabolites. Sequencing andin-silicoanalysis ofWRKYconfirmed it to be wheatTaWRKY70. Quantitative real time-PCR studies showed a higher expression ofTaWRKY70in NIL-R as compared to NIL-S afterFginoculation. Further, the functional validation ofTaWRKY70based on virus induced gene silencing (VIGS) in NIL-R, not only confirmed an increased fungal biomass but also decreased expressions of downstream resistance genes:TaACT, TaDGKandTaGLI1,along with decreased abundances of RRI metabolites biosynthesized by them. Among more than 200 FHB resistance QTL identified in wheat, this is the first QTL from which a TF was identified, and its downstream target genes as well as the FHB resistance functions were deciphered.
Risk of other Cancers in Families with Melanoma: Novel Familial Links
Authors: Frank Christoph , Sundquist Jan , Hemminki Akseli , Hemminki Kari 
Published: February 2017

AbstractA family history of cutaneous melanoma (‘melanoma’) is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.
Therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) mice
Authors: Li Jia , Chen Ying , Chen Zhibo , Huang Yuanyuan , Yang Dehao , Su Zhongqian , Weng Yiyun , Li Xiang , Zhang Xu 
Published: February 2017

AbstractThis study is to investigate the therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. EAE mouse model was established by MOG35-55 immunization. Body weight and neurological function were assessed. H&E and LFB staining was performed to evaluate histopathological changes. Flow cytometry was used to detect Th17 and Treg cells. ELISA and real-time PCR were performed to determine transcription factor and pro-inflammatory cytokine levels. Transplantation of hADSCs significantly alleviated the body weight loss and neurological function impairment of EAE mice. Inflammatory cell infiltration and demyelination were significantly increased, which were relieved by hADSC transplantation. Moreover, the Th17 cells and the ROR-γt mRNA level were significantly elevated, while the Treg cells and the Foxp3 mRNA level were significantly declined, resulting in significantly increased Th17/Treg ratio. This was reversed by the transplantation of hADSCs. Furthermore, serum levels of IL-17A, IL-6, IL-23, and TGF-β, were significantly increased, which could be influenced by the hADSC transplantation. Transplantation of hADSCs alleviates the neurological function impairment and histological changes, and reduces the inflammatory cell infiltration and demyelination in EAE mice, which might be associated with the regulation of Th17/Treg balance.
Increased nutrient availability in dense breast tissue of postmenopausal women in vivo
Authors: Abrahamsson Annelie , Rzepecka Anna , Dabrosin Charlotta 
Published: February 2017

AbstractMetabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.
A cyclometalated iridium(III) complex used as a conductor for the electrochemical sensing of IFN-γ
Authors: Miao Xiangmin , Ko Chung-Nga , Vellaisamy Kasipandi , Li Zongbing , Yang Guanjun , Leung Chung-Hang , Ma Dik-Lung 
Published: February 2017

AbstractA novel iridium(III) complex was prepared and used as a conductor for sensitive and enzyme-free electrochemical detection of interferon gamma (IFN-γ). This assay is based on a dual signal amplification mechanism involving positively charged gold nanoparticles ((+)AuNPs) and hybridization chain reaction (HCR). To construct the sensor, nafion (Nf) and (+)AuNPs composite membrane was first immobilized onto the electrode surface. Subsequently, a loop-stem structured capture probe (CP) containing a special IFN-γ interact strand was modified onto the (+)AuNP surface via the formation of Au-S bonds. Upon addition of IFN-γ, the loop-stem structure of CP was opened, and the newly exposed “sticky” region of CP then hybridized with DNA hairpin-1 (H1), which in turn opened its hairpin structure for hybridizing with DNA hairpin-2 (H2). Happen of HCR between H1 and H2 thus generated a polymeric duplex DNA (dsDNA) chain. Meanwhile, the iridium(III) complex could interact with the grooves of the dsDNA polymer, producing a strong current signal that was proportional to IFN-γ concentration. Thus, sensitive detection of IFN-γ could be realized with a detection limit down to 16.3 fM. Moreover, satisfied results were achieved by using this method for the detection of IFN-γ in human serum samples.
A Simple Method for Noninvasive Quantification of Pressure Gradient Across the Pulmonary Valve
Authors: Zhou Xueying , Xing Changyang , Feng Yang , Duan Yunyou , Zheng Qiangsun , Wang Zuojun , Liu Jie , Cao Tiesheng , Yuan Lijun 
Published: February 2017

AbstractPressure gradient across the pulmonary valve (PVPG) is an important hemodynamic variable used in the management of patients with cardiovascular and pulmonary disease. However, a reliable noninvasive method is unavailable. We hypothesized that a progressive Muller maneuver would elicit the pulmonary valve premature opening (PVPO) in diastole and that this event would be detectable by Doppler echocardiography. The intrathoracic pressure (ITP) decrease during this maneuver equals PVPG, which may be assessed with a custom airway pressure measurement device. A total of 102 subjects were enrolled in the study. At the earliest appearance of PVPO, the ITP decrease was recorded as the PVPG. PVPG was also simultaneously measured and compared by other two methods: right heart catheterization in 43 subjects, and routine Doppler echocardiography (pulmonary regurgitation jet) in the other 59 subjects. The results measured by different approaches were compared using the Bland-Altman analysis. PVPG assessed via PVPO showed strong agreement with PVPG measured by catheterization or routine Doppler echocardiography methods, with Lin concordance correlation coefficients of 0.91 and 0.70, respectively. In conclusion, PVPO provides a new noninvasive method of quantification of PVPG.
Label-free Detection of Influenza Viruses using a Reduced Graphene Oxide-based Electrochemical Immunosensor Integrated with a Microfluidic Platform
Authors: Singh Renu , Hong Seongkyeol , Jang Jaesung 
Published: February 2017

AbstractReduced graphene oxide (RGO) has recently gained considerable attention for use in electrochemical biosensing applications due to its outstanding conducting properties and large surface area. This report presents a novel microfluidic chip integrated with an RGO-based electrochemical immunosensor for label-free detection of an influenza virus, H1N1. Three microelectrodes were fabricated on a glass substrate using the photolithographic technique, and the working electrode was functionalized using RGO and monoclonal antibodies specific to the virus. These chips were integrated with polydimethylsiloxane microchannels. Structural and morphological characterizations were performed using X-ray photoelectron spectroscopy and scanning electron microscopy. Electrochemical studies revealed good selectivity and an enhanced detection limit of 0.5 PFU mL−1, where the chronoamperometric current increased linearly with H1N1 virus concentration within the range of 1 to 104 PFU mL−1 (R2 = 0.99). This microfluidic immunosensor can provide a promising platform for effective detection of biomolecules using minute samples.
Polymerase cross-linking spiral reaction (PCLSR) for detection of African swine fever virus (ASFV) in pigs and wild boars
Authors: Woźniakowski Grzegorz , Frączyk Magdalena , Kowalczyk Andrzej , Pomorska-Mól Małgorzata , Niemczuk Krzysztof , Pejsak Zygmunt 
Published: February 2017

AbstractThe study reports the development of a polymerase cross-linking spiral reaction (PCLSR) for the detection of African swine fever virus (ASFV) DNA in blood collected from infected pigs and wild boars. The method uses 3 specifically designed primers. Two outer-spiral primers comprising of 3′ sequences complementary to ASFV p72 gene sequence and 5′end sequences complementary to exogenous gene of black widow alpha-latrotoxin as well as additional ASFV specific cross-linking primer. The method is specific exclusively to ASFV DNA without cross-reactions with cDNA of classical swine fever virus (CSFV), porcine reproductive respiratory syndrome (PRRSV) or porcine epidemic diarrhea virus (PEDV). The sensitivity of this technique reached 7.2 × 102copies perμl−1of plasmid containing p72 gene. The PCLSR was conducted at 65 °C creating cross-linked complex structures. The results of PCLSR were visualized using SYBR Green I dye, gel electrophoresis while the reaction progress was traced using real-time PCR system that resulted in registration of fluorescent curves and melting peaks at 85.3 °C. The developed PCLSR was examined using blood or tissue samples collected from selected 17 ASF cases from infected wild boars and 3 outbreaks in pigs. Further tests have been also conducted using 55 tissue samples from 23 outbreaks and 22 cases. These results showed that PCLSR might be further used for preliminary and cost-effective detection and surveillance of ASFV.
Degradation of structure and properties of rail surface layer at long-term operation
Authors: Gromov V. E. , Ivanov Yu. F. , Qin R. S. , Peregudov O. A. , Aksenova K. V. , Semina O. A. 
Published: February 2017

The microstructure evolution and properties variation of the surface layer of rail steel after passed 500 and 1000 million tons of gross weight (MTGW) have been investigated. The wear rate increases to 3 and 3.4 times after passed 500 and 1000 MTGW, respectively. The corresponding friction coefficient decreases by 1.4 and 1.1 times. The cementite plates were destroyed and formed the cementite particles of around 10–50nm in size after passed 500 MTGW. The early stage dynamical recrystallisation was observed after passed 1000 MTGW. The mechanisms for these have been suggested. The large number of bend extinction contours is revealed in the surface layer. The internal stress field is evaluated. This paper is part of a themed issue on Materials in External Fields.
Comparisons of absolute gravimeters (COOMET.M.G-S1)
Authors: Vinnichenko Mr Alexander , Germak Dr Alessandro 
Published: February 2017

This report describes the results of the RMO supplementary comparison COOMET.M.G-S1 (also known as bilateral comparison COOMET 634/UA/14). The comparison measurements between the two participants NSC 'IM' (pilot laboratory) and INRIM were started in December 2015 and finished in January 2016.
Participants of comparisons were conducted at their national standards the measurements of the free fall acceleration in gravimetric point laboratory of absolute gravimetry of INRIM named INRiM.2. Absolute measurements of gravimetric acceleration were conducted by ballistic gravimeters.
The agreement between the two participants is good.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.
The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).