bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection against inhalation anthrax by immunization with Salmonella enterica serovar Typhi Ty21a stably producing protective antigen of Bacillus anthracis
Authors: Sim B. Kim Lee , Li Minglin , Osorio Manuel , Wu Yun , Wai Tint T. , Peterson Johnny W. , James Eric R. , Chakravarty Sumana , Gao Lixin , Xu Rui , KC Natasha , Stafford Richard E. , Lawrence William S. , Yeager Linsey A. , Peel Jennifer E. , Sivasubramani Satheesh K. , Chopra Ashok K. , Filippova Svetlana , Hoffman Stephen L. 
Published: June 2017

AbstractThe national blueprint for biodefense concluded that the United States is underprepared for biological threats. The licensed anthrax vaccine absorbed vaccine, BioThrax, requires administration of at least 3–5 intramuscular doses. The anthrax vaccine absorbed vaccine consists of complex cell-free culture filtrates of a toxigenic Bacillus anthracis strain and causes tenderness at the injection site and significant adverse events. We integrated a codon-optimized, protective antigen gene of B. anthracis (plus extracellular secretion machinery), into the chromosome of the licensed, oral, live-attenuated typhoid fever vaccineTy21a to form Ty21a-PA-01 and demonstrated excellent expression of the gene encoding protective antigen. We produced the vaccine in a 10-L fermenter; foam-dried and vialed it, and characterized the dried product. The vaccine retained ~50% viability for 20 months at ambient temperature. Sera from animals immunized by the intraperitoneal route had high levels of anti-protective antigen antibodies by enzyme-linked immunosorbent assay and anthrax lethal toxin-neutralizing activity. Immunized mice were fully protected against intranasal challenge with ~5 LD50 of B. anthracis Sterne spores, and 70% (7/10) of vaccinated rabbits were protected against aerosol challenge with 200 LD50 of B. anthracis Ames spores. There was a significant correlation between protection and antibody levels determined by enzyme-linked immunosorbent assay and toxin-neutralizing activity. These data provide the foundation for achievement of our ultimate goal, which is to develop an oral anthrax vaccine that is stable at ambient temperatures and induces the rapid onset of durable, high-level protection after a 1-week immunization regimen.
mTFkb: a knowledgebase for fundamental annotation of mouse transcription factors
Authors: Sun Kun , Wang Huating , Sun Hao 
Published: June 2017

AbstractTranscription factors (TFs) are well-known important regulators in cell biology and tissue development. However, in mouse, one of the most widely-used model species, currently the vast majority of the known TFs have not been functionally studied due to the lack of sufficient annotations. To this end, we collected and analyzed the whole transcriptome sequencing data from more than 30 major mouse tissues and used the expression profiles to annotate the TFs. We found that the expression patterns of the TFs are highly correlated with the histology of the tissue types thus can be used to infer the potential functions of the TFs. Furthermore, we found that as many as 30% TFs display tissue-specific expression pattern, and these tissue-specific TFs are among the key TFs in their corresponding tissues. We also observed signals of divergent transcription associated with many TFs with unique expression pattern. Lastly, we have integrated all the data, our analysis results as well as various annotation resources to build a web-based database named mTFkb freely accessible at htt﻿p://www.m﻿yogenesisdb.org/mTFkb/. We believe that mTFkb could serve as a useful and valuable resource for TF studies in mouse.
Leukocyte Bim deficiency does not impact atherogenesis in ldlr
−/− mice, despite a pronounced induction of autoimmune inflammation
Authors: Temmerman Lieve , Westra Marijke M. , Bot Ilze , van Vlijmen Bart J. M. , van Bree Niek , Bot Martine , Habets Kim L. L. , Keulers Tom G. H. , van der Vlag Johan , Cotter Thomas G. , van Berkel Theo J. C. , Biessen Erik A. L. 
Published: June 2017

AbstractProapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim−/− or wild type bone marrow transplanted ldlr−/− mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed. Bim−/− transplanted mice displayed splenomegaly and overt lymphocytosis. CD4+ and CD8+ T cells were more activated (increased CD69 and CD71 expression, increased interferon gamma production). B cells were elevated by 147%, with a shift towards the pro-atherogenic IgG-producing B2 cell phenotype, resulting in a doubling of anti-oxLDL IgG1 antibody titers in serum of bim−/− mice. Bim−/− mice displayed massive intraplaque accumulation of Ig complexes and of lesional T cells, although this did not translate in changes in plaque size or stability features (apoptotic cell and macrophage content). The surprising lack in plaque phenotype despite the profound pro-atherogenic immune effects may be attributable to the sharp reduction of serum cholesterol levels in WTD fed bim−/− mice.
Controlled functional expression of the bacteriocins pediocin PA-1 and bactofencin A in Escherichia coli
Authors: Mesa-Pereira Beatriz , O’Connor Paula M. , Rea Mary C. , Cotter Paul D. , Hill Colin , Ross R. Paul 
Published: June 2017

AbstractThe bacteriocins bactofencin A (class IId) and pediocin PA-1 (class IIa) are encoded by operons with a similarly clustered gene organization including a structural peptide, an immunity protein, an ABC transporter and accessory bacteriocin transporter protein. Cloning of these operons in E. coli TunerTM (DE3) on a pETcoco-2 derived vector resulted in successful secretion of both bacteriocins. A corresponding approach, involving the construction of vectors containing different combinations of these genes, revealed that the structural and the transporter genes alone are sufficient to permit heterologous production and secretion in this host. Even though the accessory protein, usually associated with optimal disulfide bond formation, was not required for bacteriocin synthesis, its presence did result in greater pediocin PA-1 production. The simplicity of the system and the fact that the associated bacteriocins could be recovered from the extracellular medium provides an opportunity to facilitate protein engineering and the overproduction of biologically-active bacteriocins at industrial scale. Additionally, this system could enable the characterization of new bacteriocin operons where genetic tools are not available for the native producers.
RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice
Authors: Noguchi Hirofumi , Sugimoto Koji , Miyagi-Shiohira Chika , Nakashima Yoshiki , Kobayashi Naoya , Saitoh Issei , Watanabe Masami , Noguchi Yasufumi 
Published: June 2017

AbstractCalcineurin inhibitors have been used for transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide (11R-VIVIT) selectively interferes with calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase and provides immunosuppression for fully mismatched islet allografts in mice. However, our recent study showed that 11R-VIVIT affected cell viability in vitro when it was used at higher concentration because of the VIVIT sequence. The aim of this study is to develop a safer NFAT inhibitor (RCAN-11R) that does not affect cell viability, and which is less toxic than calcineurin inhibitors. The minimal sequence of the protein family of regulators of calcineurin (RCAN) that is responsible for the inhibition of calcineurin-NFAT signaling was recently characterized. The peptide could selectively interfere with the calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase, similar to 11R-VIVIT. RCAN-11R did not affect cell viability when it was used at a higher concentration than the toxic concentration of 11R-VIVIT. RCAN-11R could therefore be useful as a therapeutic agent that is less toxic than current drugs or 11R-VIVIT.
Geographic variation in pneumococcal vaccine efficacy estimated from dynamic modeling of epidemiological data post-PCV7
Authors: Gjini Erida 
Published: June 2017

AbstractAlthough mean efficacy of multivalent pneumococcus vaccines has been intensively studied, variance in vaccine efficacy (VE) has been overlooked. Different net individual protection across settings can be driven by environmental conditions, local serotype and clonal composition, as well as by socio-demographic and genetic host factors. Understanding efficacy variation has implications for population-level effectiveness and other eco-evolutionary feedbacks. Here I show that realized VE can vary across epidemiological settings, by applying a multi-site-one-model approach to data post-vaccination. I analyse serotype prevalence dynamics following PCV7, in asymptomatic carriage in children attending day care in Portugal, Norway, France, Greece, Hungary and Hong-Kong. Model fitting to each dataset provides site-specific estimates for vaccine efficacy against acquisition, and pneumococcal transmission parameters. According to this model, variable serotype replacement across sites can be explained through variable PCV7 efficacy, ranging from 40% in Norway to 10% in Hong-Kong. While the details of how this effect is achieved remain to be determined, here I report three factors negatively associated with the VE readout, including initial prevalence of serotype 19F, daily mean temperature, and the Gini index. The study warrants more attention on local modulators of vaccine performance and calls for predictive frameworks within and across populations.
Storage of neural histamine and histaminergic neurotransmission is VMAT2 dependent in the zebrafish
Authors: Puttonen Henri A. J. , Semenova Svetlana , Sundvik Maria , Panula Pertti 
Published: June 2017

AbstractMonoaminergic neurotransmission is greatly dependent on the function of the vesicular monoamine transporter VMAT2, which is responsible for loading monoamines into secretory vesicles. The role of VMAT2 in histaminergic neurotransmission is poorly understood. We studied the structure and function of the histaminergic system in larval zebrafish following inhibition of VMAT2 function by reserpine. We found that reserpine treatment greatly reduced histamine immunoreactivity in neurons and an almost total disappearance of histamine-containing nerve fibers in the dorsal telencephalon and habenula, the most densely innervated targets of the hypothalamic histamine neurons. The reserpine treated larvae had an impaired histamine-dependent dark-induced flash response seen during the first second after onset of darkness, implying that function of the histaminergic network is VMAT2 dependent. Levels of histamine and other monoamines were decreased in reserpine treated animals. This study provides conclusive evidence of the relevance of VMAT2 in histaminergic neurotransmission, further implying that the storage and release mechanism of neural histamine is comparable to that of other monoamines. Our results also reveal potential new insights about the roles of monoaminergic neurotransmitters in the regulation of locomotion increase during adaptation to darkness.
Detection of DNA Amplicons of Polymerase Chain Reaction Using Litmus Test
Authors: Chang Dingran , Tram Kha , Li Ben , Feng Qian , Shen Zhifa , Lee Christine H. , Salena Bruno J. , Li Yingfu 
Published: June 2017

AbstractWe report on a new colorimetric DNA detection method that takes advantage of the power of polymerase chain reaction (PCR) and the simplicity of the classic litmus test. The strategy makes use of a modified set of primers for PCR to facilitate ensuing manipulations of resultant DNA amplicons: their tagging with urease and immobilization onto magnetic beads. The amplicon/urease-laden beads are then used to hydrolyze urea, resulting in the increase of pH that can be conveniently reported by a pH-sensitive dye. We have successfully applied this strategy for the detection of two hypervirulent strains of the bacterium Clostridium difficile that are responsible for the recent increase in the global incidence and severity of C. difficile infections. Furthermore, the viability of this test for diagnostic applications is demonstrated using clinically validated stool samples from C. difficile infected patients.
Comprehensive study of excess phosphate response reveals ethylene mediated signaling that negatively regulates plant growth and development
Authors: Shukla Devesh , Rinehart Claire A. , Sahi Shivendra V. 
Published: June 2017

AbstractExcess Phosphorus (P) in agriculture is causing serious environmental problems like eutrophication of lakes and rivers. Unlike the enormous information available for phosphate starvation response (P0), very few information is available for the effect of excess phosphate Pi on plants. Characterization of Excess Phosphate Response (EPiR) is essential for designing strategies to increase phosphate accumulation and tolerance. We show a significant modulation in the root developmental plasticity under the increasing supply of excess Pi. An excess supply of 20 mM Pi (P20) produces a shallow root system architecture (RSA), reduces primary root growth, root apical meristem size, and meristematic activity in Arabidopsis. The inhibition of primary root growth and development is indeterminate in nature and caused by the decrease in number of meristematic cortical cells due to EPiR. Significant changes occurred in metal nutrients level due to excess Pi supply. A comparative microarray investigation of the EPiR response reveals a modulation in ethylene biosynthesis and signaling, metal ions deficiency response, and root development related genes. We used ethylene-insensitive or sensitive mutants to provide more evidence for ethylene-mediated signaling. A new role of EPiR in regulating the developmental responses of plants mediated by ethylene has been demonstrated.
Optical mapping of neuronal activity during seizures in zebrafish
Authors: Turrini L. , Fornetto C. , Marchetto G. , Müllenbroich M. C. , Tiso N. , Vettori A. , Resta F. , Masi A. , Mannaioni G. , Pavone F. S. , Vanzi F. 
Published: June 2017

AbstractMapping neuronal activity during the onset and propagation of epileptic seizures can provide a better understanding of the mechanisms underlying this pathology and improve our approaches to the development of new drugs. Recently, zebrafish has become an important model for studying epilepsy both in basic research and in drug discovery. Here, we employed a transgenic line with pan-neuronal expression of the genetically-encoded calcium indicator GCaMP6s to measure neuronal activity in zebrafish larvae during seizures induced by pentylenetretrazole (PTZ). With this approach, we mapped neuronal activity in different areas of the larval brain, demonstrating the high sensitivity of this method to different levels of alteration, as induced by increasing PTZ concentrations, and the rescuing effect of an anti-epileptic drug. We also present simultaneous measurements of brain and locomotor activity, as well as a high-throughput assay, demonstrating that GCaMP measurements can complement behavioural assays for the detection of subclinical epileptic seizures, thus enabling future investigations on human hypomorphic mutations and more effective drug screening methods. Notably, the methodology described here can be easily applied to the study of many human neuropathologies modelled in zebrafish, allowing a simple and yet detailed investigation of brain activity alterations associated with the pathological phenotype.
Prenatal chromium exposure and risk of preterm birth: a cohort study in Hubei, China
Authors: Pan Xinyun , Hu Jie , Xia Wei , Zhang Bin , Liu Wenyu , Zhang Chuncao , Yang Jie , Hu Chen , Zhou Aifen , Chen Zhong , Cao Jiangxia , Zhang Yiming , Wang Youjie , Huang Zheng , Lv Bin , Song Ranran , Zhang Jianduan , Xu Shunqing , Li Yuanyuan 
Published: June 2017

AbstractFew studies have investigated the association of environmental chromium exposure and preterm birth in general population. This study was designed to investigate whether maternal chromium exposure during pregnancy is associated with reduced gestational age or risk of preterm birth using the data from Healthy Baby Cohort study conducted in Hubei, China between 2012 and 2014 (n = 7290). Chromium concentrations in maternal urine samples collected at delivery were measured with inductively coupled plasma mass spectrometry. Tertiles of chromium concentrations was negatively associated with gestational age in multivariable linear regression analyses [β (95% CI): low = reference; middle = −0.67 days (−1.14, −0.20); high = −2.30 days (−2.93, −1.67); p trend <0.01]. Logistic regression analyses also indicated that higher maternal chromium [adjusted odds ratio (OR) (95% CI): 1.55(0.99, 2.42) for the medium tertile; 1.89(1.13, 3.18) for the highest tertile; p trend <0.01] was associated with increased risk of preterm birth. The associations appeared to be more pronounced in male infants (adjusted OR (95% CI): 2.54 (1.29, 4.95) for the medium tertile; 2.92 (1.37, 6.19) for the highest tertile; p trend <0.01). Our findings suggest maternal exposure to higher chromium levels during pregnancy may potentially increase the risk of delivering preterm infants, particularly for male infants.
Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter
Authors: Radic-Sarikas Branka , Halasz Melinda , Huber Kilian V. M. , Winter Georg E. , Tsafou Kalliopi P. , Papamarkou Theodore , Brunak Søren , Kolch Walter , Superti-Furga Giulio 
Published: June 2017

AbstractAdverse side effects of cancer agents are of great concern in the context of childhood tumors where they can reduce the quality of life in young patients and cause life-long adverse effects. Synergistic drug combinations can lessen potential toxic side effects through lower dosing and simultaneously help to overcome drug resistance. Neuroblastoma is the most common cancer in infancy and extremely heterogeneous in clinical presentation and features. Applying a systematic pairwise drug combination screen we observed a highly potent synergy in neuroblastoma cells between the EGFR kinase inhibitor lapatinib and the anticancer compound YM155 that is preserved across several neuroblastoma variants. Mechanistically, the synergy was based on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is frequently expressed in resistant neuroblastoma cells, which allowed prolonged and elevated cytotoxicity of YM155. In addition, the drug combination (i.e. lapatinib plus YM155) decreased neuroblastoma tumor size in an in vivo model.
Characterization of a new murine cell line of sarcomatoid hepatocellular carcinoma and its application for biomarker/therapy development
Authors: Yen Chia-Hung , Lai Chih-Chung , Liao Chen-Chung , Wang Sheng-Fan , Liao Yi-Jen , Tung Chien-Yi , Hung Jung-Hsien , Huang Shiu-Feng , Chen Yi-Ming Arthur 
Published: June 2017

AbstractSarcomatoid hepatocellular carcinoma (SHC) is a rare type of HCC with significantly poorer survival than ordinary HCC. Little is known about the mechanism associated with SHC and its biomarkers and therapy. Here, we established a mouse liver cancer cell line and designated as Ymac-1. A sarcomatous appearance was observed in the allograft tumor arose from Ymac-1. Liver-secreted plasma proteins were found in Ymac-1 cultured supernatant by proteomics analysis. The positive staining of CK7, CK8, Vimentin and the suppressed expression of AFP indicated that Ymac-1 is a SHC cell line. Compared to its original tumor, an elevated level of EMT markers, N-cadherin and Vimentin, was found in Ymac-1. Ymac-1 displayed a higher migration rate and side population percentage than a mouse ordinary HCC cell line-Hepa1-6. Microarray analysis was performed to identify potential biomarkers/therapeutic targets for SHC. G6pd, a vital enzyme in pentose phosphate pathway, is highly expressed in Ymac-1. Depletion of G6pd in Ymac-1 reduced CD133 expression and sphere formation. Positive correlations between G6PD and CD133 were observed in human specimen. Higher expression of both G6PD and CD133 in tumor were associated with poor survival. In summary Ymac-1 can be a useful SHC cell model for novel biomarker and therapy development.
Sortase A-mediated crosslinked short-chain dehydrogenases/reductases as novel biocatalysts with improved thermostability and catalytic efficiency
Authors: Li Kunpeng , Zhang Rongzhen , Xu Yan , Wu Zhimeng , Li Jing , Zhou Xiaotian , Jiang Jiawei , Liu Haiyan , Xiao Rong 
Published: June 2017

Abstract(S)-carbonyl reductase II (SCRII) from Candida parapsilosis is a short-chain alcohol dehydrogenase/reductase. It catalyses the conversion of 2-hydroxyacetophenone to (S)-1-phenyl-1,2-ethanediol with low efficiency. Sortase was reported as a molecular “stapler” for site-specific protein conjugation to strengthen or add protein functionality. Here, we describe Staphylococcus aureus sortase A-mediated crosslinking of SCRII to produce stable catalysts for efficient biotransformation. Via a native N-terminal glycine and an added GGGGSLPETGG peptide at C-terminus of SCRII, SCRII subunits were conjugated by sortase A to form crosslinked SCRII, mainly dimers and trimers. The crosslinked SCRII showed over 6-fold and 4-fold increases, respectively, in activity and kcat/Km values toward 2-hydroxyacetophenone compared with wild-type SCRII. Moreover, crosslinked SCRII was much more thermostable with its denaturation temperature (Tm) increased to 60 °C. Biotransformation result showed that crosslinked SCRII gave a product optical purity of 100% and a yield of >99.9% within 3 h, a 16-fold decrease in transformation duration with respect to Escherichia coli/pET-SCRII. Sortase A-catalysed ligation also obviously improved Tms and product yields of eight other short-chain alcohol dehydrogenases/reductases. This work demonstrates a generic technology to improve enzyme function and thermostability through sortase A-mediated crosslinking of oxidoreductases.