bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropeptides PDF and DH31 hierarchically regulate free-running rhythmicity in Drosophila circadian locomotor activity
Authors: Goda Tadahiro , Umezaki Yujiro , Alwattari Fay , Seo Hanna W. , Hamada Fumika N.
Published: January 2019

Neuropeptides play pivotal roles in modulating circadian rhythms. Pigment-dispersing factor (PDF) is critical to the circadian rhythms in Drosophila locomotor activity. Here, we demonstrate that diuretic hormone 31 (DH31) complements PDF function in regulating free-running rhythmicity using male flies. We determined that Dh31 loss-of-function mutants (Dh31#51) showed normal rhythmicity, whereas Dh31#51;Pdf01 double mutants exhibited a severe arrhythmic phenotype compared to Pdf-null mutants (Pdf01). The expression of tethered-PDF or tethered-DH31 in clock cells, posterior dorsal neurons 1 (DN1ps), overcomes the severe arrhythmicity of Dh31#51;Pdf01 double mutants, suggesting that DH31 and PDF may act on DN1ps to regulate free-running rhythmicity in a hierarchical manner. Unexpectedly, the molecular oscillations in Dh31#51;Pdf01 mutants were similar to those in Pdf01 mutants in DN1ps, indicating that DH31 does not contribute to molecular oscillations. Furthermore, a reduction in Dh31 receptor (Dh31r) expression resulted in normal locomotor activity and did not enhance the arrhythmic phenotype caused by the Pdf receptor (Pdfr) mutation, suggesting that PDFR, but not DH31R, in DN1ps mainly regulates free-running rhythmicity. Taken together, we identify a novel role of DH31, in which DH31 and PDF hierarchically regulate free-running rhythmicity through DN1ps.
Semen levels of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinases (TIMP) protein families members in men with high and low sperm DNA fragmentation
Authors: Belardin Larissa Berloffa , Antoniassi Mariana Pereira , Camargo Mariana , Intasqui Paula , Fraietta Renato , Bertolla Ricardo Pimenta
Published: January 2019

Matrix Metalloproteinases (MMPs) and their regulators – Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) – participate in extracellular matrix remodeling, fibrosis, and semen liquefaction, as well as to inflammatory activity. Seminal plasma has been shown to contain MMPs (MMP-2 and MMP-9) and TIMPs (TIMP-1 and TIMP-2). Also, a link between MMPs gene expression and excessive reactive oxygen species (ROS) has been established. In semen, ROS are associated with altered sperm function and increased DNA fragmentation. In this study, it is hypothesized that seminal MMPs and TIMPs levels are associated with sperm DNA fragmentation due to the fact that MMPs have been associated with semen quality. We also hypothesized that these proteins could predict DNA fragmentation status in sperm. Therefore, this study set out to verify if sperm DNA fragmentation levels relate to seminal levels of members of the MMP and TIMP protein families. The High sperm DNA fragmentation group presented lower seminal plasma levels of MMP-2, MMP-7, TIMP-1, TIMP-2 and TIMP-4 when compared to Low sperm DNA fragmentation group. Also, samples in the high sperm DNA fragmentation group presented higher acrosome integrity and lower mitochondrial activity levels when compared to low sperm DNA fragmentation samples. In the logistic regression analysis, MMP-2, MMP-7, and TIMP-4 classified samples as low and high sperm DNA fragmentation, with an overall model fit of 74.5%. Results from this study may demonstrate a specific inflammatory mechanism in samples with high sperm DNA fragmentation. This, in turn, can lead to the development of new studies regarding this mechanism and, in the future, create an opportunity to treat these patients for sperm DNA fragmentation by treating inflammatory seminal activity.
Tsc1 ablation in Prx1 and Osterix lineages causes renal cystogenesis in mouse
Authors: Wu Zhixiang , Wu Hongguang , Md Shafiquzzaman , Yu Guo , Habib Samy L. , Li Baojie , Li Jing
Published: January 2019

Tuberous Sclerosis Complex (TSC) is caused by mutations in TSC1 or TSC2, which encode negative regulators of the mTOR signaling pathway. The renal abnormalities associated with TSC include angiomyolipoma, cysts, and renal cell carcinoma. Here we report that specific ablation of Tsc1 using the mesenchymal stem cell-osteoblast lineage markers induced cystogenesis in mice. Using Rosa-tdTomato mice, we found that Prx1- or Dermo1-labeled cells were present in the nephron including glomerulus but they were not stained by markers for podocytes, mesangial cells, endothelial cells, or proximal or loop of Henle tubular cells, while Osx is known to label tubular cells. Tsc1 deficiency in Prx1 lineage cells caused development of mild cysts that were positive only for Tamm-Horsfall protein (THP), a loop of Henle marker, while Tsc1 deficiency in Osx lineage cells caused development of cysts that were positive for Villin, a proximal tubular cell marker. On the other hand, Tsc1 deficiency in the Dermo1 lineage did not produce detectable phenotypical changes in the kidney. Cyst formation in Prx1-Cre; Tsc1f/f and Osx-Cre; Tsc1f/f mice were associated with increase in both proliferative and apoptotic cells in the affected tissue and were largely suppressed by rapamycin. These results suggest that Prx1 and Osx lineages cells may contribute to renal cystogenesis in TSC patients.
Mixed Viral-Bacterial Infections and Their Effects on Gut Microbiota and Clinical Illnesses in Children
Authors: Mathew Shilu , Smatti Maria K. , Al Ansari Khalid , Nasrallah Gheyath K. , Al Thani Asmaa A. , Yassine Hadi M.
Published: January 2019

Acute gastroenteritis remains a major cause of morbidity and mortality among young children worldwide. It accounts for approximately 1.34 million deaths annually in children younger than five years. Infection can be caused by viral, bacterial and/or parasitic microorganisms. Dysbiosis due to such infections could dramatically affect disease prognosis as well as development of chronic illness. The aim of this study was to analyze gut microbiome and clinical outcomes in young children suffering from viral or mixed viral-bacterial infection. We evaluated gut microbiota composition in children suffering from viral or mixed viral-bacterial infection with two major viruses rotavirus (RV) and norovirus (NoV) and two pathogenic bacteria [Enteroaggregative E. coli (EAEC), and Enteropathogenic E. coli (EPEC)]. We sequenced 16S ribosomal RNA (V4 region) genes using Illumina MiSeq in 70 hospitalized children suffering from gastroenteric infections plus nine healthy controls. The study summarized Operational Taxonomic Unit (OTU) abundances with the Bray-Curtis index and performed a non-metric multidimensional scaling analysis to visualize microbiome similarities. We used a permutational multivariate analyses of variance to test the significance of group differences. We also analyzed the correlation between microbiome changes and clinical outcomes. Our data demonstrated a significant increase in the severity score in children with viral-bacterial mixed infections compared to those with virus infections alone. Statistical analysis by overall relative abundance denoted lesser proportions of Bacteroides in the infected children, whereas Bifidobacteriaceae richness was more prominent in the bacterial-viral mixed infections. Pairwise differences of gut microbiota were significantly higher in RV + EAEC (P = 0.009) and NoV + EAEC (P = 0.009) co-infections, compared to EPEC mixed infection with both, RV (P = 0.045) and NoV (P = 0.188). Shannon diversity index showed considerable more variation in microbiome diversity in children infected with RV cohort compared to NoV cohort. Our results highlight that richness of Bifidobacteriaceae, which acts as probiotics, increased with the severity of the viral-bacterial mixed infections. As expected, significant reduction of relative numbers of Bacteroides was characterized in both RV and NoV infections, with more reduction observed in co-infection pathogenic E. coli. Although mixed infection with EAEC resulted in significant microbiota differences compared to viral infection only or mixed infection with EPEC, the clinical condition of the children were worsened with both pathogenic E.coli co-infections. Further, in comparison with RV cohort, augmented number of differential abundant pathogenic OTUs were peculiarly noticed only with NoV mixed infection.
Melamine promotes calcium crystal formation in three-dimensional microfluidic device
Authors: Gombedza Farai , Evans Sade , Shin Samuel , Awuah Boadi Eugenia , Zhang Qian , Nie Zhihong , Bandyopadhyay Bidhan C.
Published: January 2019

Melamine, which induces proximal tubular (PT) cell damage has a greater nephrotoxic effect when combined with cyanuric and uric acids; however, it is unknown whether such effect can stimulate calcium phosphate (CaP)/calcium oxalate (CaOx) stone formation. Here, we show that melamine acts as an inducer of CaP, CaOx and CaP + CaOx (mixed) crystal formations in a time and concentration-dependent manner by stabilizing those crystals and further co-aggregating with melamine. To explore the physiological relevance of such melamine-augmented calcium crystal formation, we used 2-dimensional (2D) and 3D microfluidic (MF) device, embedded with PT cells, which also resembled the effect of melamine-stimulated CaP, CaOx and mixed crystal formation. Significantly, addition of preformed CaP and/or CaOx crystal in the presence of melamine, further potentiated those crystal formations in 3D MFs, which helped the growth and aggregation of mixed crystals. Our data show that the mechanism of such predisposition of stone formation could be largely due to co-crystallization between melamine and CaP/CaOx and pronounced effect on induction of stone-forming pathway activation in 3D MF. Taken together, melamine-induced CaP and/or CaOx crystal formation ex-vivo will help us in understanding the larger role of melamine as an environmental toxicant in producing the pathology in similar cellular microenvironments.
Genome wide association study of body weight and feed efficiency traits in a commercial broiler chicken population, a re-visitation
Authors: Mebratie Wossenie , Reyer Henry , Wimmers Klaus , Bovenhuis Henk , Jensen Just
Published: January 2019

Genome wide association study was conducted using a mixed linear model (MLM) approach that accounted for family structure to identify single nucleotide polymorphisms (SNPs) and candidate genes associated with body weight (BW) and feed efficiency (FE) traits in a broiler chicken population. The results of the MLM approach were compared with the results of a general linear model approach that does not take family structure in to account. In total, 11 quantitative trait loci (QTL) and 21 SNPs, were identified to be significantly associated with BW traits and 5 QTL and 5 SNPs were found associated with FE traits using MLM approach. Besides some overlaps between the results of the two GWAS approaches, there are considerable differences in the detected QTL. Even though the genomic inflation factor (λ) values indicate that there is no strong family structure in this population, using models that account for the existing family structure may reduce bias and increase accuracy of the estimated SNP effects in the association analysis. The SNPs and candidate genes identified in this study provide information on the genetic background of BW and FE traits in broiler chickens and might be used as prior information for genomic selection.
Confinement induces helical organization of chromosome-like polymers
Authors: Jung Youngkyun , Ha Bae-Yeun
Published: January 2019

Helical organization is commonly observed for a variety of biopolymers. Here we study the helical organization of two types of biopolymers, i.e., DNA-like semiflexible and bottle-brush polymers, in a cell-like confined space. A bottle-brush polymer consists of a backbone and side chains emanating from the backbone, resembling a supercoiled bacterial chromosome. Using computer simulations, we calculate ‘writhe’ distributions of confined biopolymers for a wide range of parameters. Our effort clarifies the conditions under which biopolymers are helically organized. While helical organization is not easily realized for DNA-like biomolecules, cylindrical confinement can induce spiral patterns in a bottle brush, similarly to what was observed with bacterial chromosomes. They also suggest that ring-shape bottle brushes have a stronger tendency for helical organization. We discuss how our results can be used to interpret chromosome experiments. For instance, they suggest that experimental resolution has unexpected consequences on writhe measurements (e.g., narrowing of the writhe distribution and kinetic separation of opposite helical states).
Tryptophan usage by Helicobacter pylori differs among strains
Authors: Rojas-Rengifo Diana F. , Ulloa-Guerrero Cindy P. , Joppich Markus , Haas Rainer , del Pilar Delgado Maria , Jaramillo Carlos , Jiménez-Soto Luisa F.
Published: January 2019

Because of its association with severe gastric pathologies, including gastric cancer,Helicobacter pylorihas been subject of research for more than 30 years. Its capacity to adapt and survive in the human stomach can be attributed to its genetic flexibility. Its natural competence and its capacity to turn genes on and off allowsH. pylorito adapt rapidly to the changing conditions of its host. Because of its genetic variability, it is difficult to establish the uniqueness of each strain obtained from a human host. The methods considered to-date to deliver the best result for differentiation of strains are Rapid Amplification of Polymorphic DNA (RAPD), Multilocus Sequence Typing (MLST) and Whole Genome Sequencing (WGS) analysis. While RAPD analysis is cost-effective, it requires a stable genome for its reliability. MLST and WGS are optimal for strain identification, however, they require analysis of data at the bioinformatics level. Using the StainFree method, which modifies tryptophan residues on proteins using 2, 2, 2, - trichloroethanol (TCE), we observed a strain specific pattern of tryptophan in 1D acrylamide gels. In order to establish the effectiveness of tryptophan fingerprinting for strain identification, we compared the graphic analysis of tryptophan-labelled bands in the gel images with MLST results. Based on this, we find that tryptophan banding patterns can be used as an alternative method for the differentiation ofH. pyloristrains. Furthermore, investigating the origin for these differences, we found thatH. pyloristrains alters the number and/or position of tryptophan present in several proteins at the genetic code level, with most exchanges taking place in membrane- and cation-binding proteins, which could be part of a novel response ofH. pylorito host adaptation.
Ecological drivers of marine debris ingestion in Procellariiform Seabirds
Authors: Roman Lauren , Bell Elizabeth , Wilcox Chris , Hardesty Britta Denise , Hindell Mark
Published: January 2019

Procellariiform seabirds are both the most threatened bird group globally, and the group with the highest incidence of marine debris ingestion. We examined the incidence and ecological factors associated with marine debris ingestion in Procellariiformes by examining seabirds collected at a global seabird hotspot, the Australasian - Southern Ocean boundary. We examined marine debris ingestion trends in 1734 individuals of 51 Procellariform species, finding significant variation in the incidence of marine debris abundance among species. Variation in the incidence of marine debris ingestion between species was influenced by the taxonomy, foraging ecology, diet, and foraging range overlaps with oceanic regions polluted with marine debris. Among the ecological drivers of marine debris ingestion variability in Procellariiformes, we demonstrate that the combination of taxonomy, foraging method, diet, and exposure to marine debris are the most important determinants of incidence of ingestion. We use these results to develop a global forecast for Procellariiform taxa at the risk of highest incidence of marine debris ingestion. We find seabirds that forage at the surface; especially by surface seizing, diving and filtering, those with a crustacean dominant diet, and those that forage in or near marine debris hotspots are at highest risk of debris ingestion. We predict that family with the highest risk are the storm petrels (Hydrobatidae and Oceanitidae). We demonstrate that the greater the exposure of high-risk groups to marine debris while foraging, the greater the incidence and number of marine debris items will be ingested.
Feasible and effective reuse of municipal sludge for vegetation restoration: physiochemical characteristics and microbial diversity
Authors: Liu Xueya , Liu Lijuan , Leng Pingsheng , Hu Zenghui
Published: January 2019

The large volume of municipal sludge causes environmental problems in cities worldwide. In this study, municipal sludge, mixed with construction waste residue, was used as substrate to plant Ailanthus altissima. The growth of A. altissima, the substrate characteristics, and substrate microbial diversity were measured to investigate potential recycling and reusing pathways of municipal sludge. The obtained results showed that compared to garden soil, the mixed substrate was weakly alkaline, and had higher nutrient contents, which is beneficial for A. altissima, and results in better growth in mixed substrate. Although the contents of the main heavy metals in the mixed substrate were significantly higher than in garden soil, the values met the criterion of Class II soil in the Environmental Quality Standard for the Soils of China (GB15618-1995). Different substrates showed a variety of microbial diversities. Proteobacteria was the top microbial phylum in all samples, and higher relative abundances were found in samples containing municipal sludge. After growing A. altissima, the relative abundances of Acidobacteria and Gemmatimonadetes increased in the mixed substrate. Therefore, addition of construction waste residue and growth of A. altissima caused a difference. The microbial communities in the mixed substrate with A. altissima are both plant friendly and environmentally friendly. These results suggest this mixed substrate as a potentially feasible and effective pathway for the reuse and recycling of municipal sludge for vegetation restoration.
Comprehensive profiling of JMJD3 in gastric cancer and its influence on patient survival
Authors: Xu Zhenyu , Xia Yabin , Xiao Zhangang , Jia Yuliang , Li Lina , Jin Yan , Zhao Qijie , Wan Lin , Yi Tao , Yu Yangyang , Wen Qinglian , Zhu Yinxin , Qin Bo , Zhang Fan , Shen Jing
Published: January 2019

Histone methylation is thought to control the regulation of genetic program and the dysregulation of it has been found to be closely associated with cancer. JMJD3 has been identified as an H3K27 demethylase and its role in cancer development is context specific. The role of JMJD3 in gastric cancer (GC) has not been examined. In this study, JMJD3 expression was determined. The prognostic significance of JMJD3 and its association with clinical parameters were evaluated. JMJD3 dysregulation mechanism and targets were analyzed. The effect of JMJD3 mutation was determined by functional study. Results showed that JMJD3 was overexpressed in different patient cohorts and also by bioinformatics analysis. High JMJD3 expression was correlated with shortened overall survival in patients with GC and was an independent prognosis predictor. Genetic aberration and DNA methylation might be involved in the deregulation of JMJD3 in GC. Downstream network of JMJD3 was analyzed and several novel potential targets were identified. Furthermore, functional study discovered that both demethylase-dependent and demethylase-independent mechanisms were involved in the oncogenic role of JMJD3 in GC. Importantly, histone demethylase inhibitor GSK-J4 could reverse the oncogenic effect of JMJD3 overexpression. In conclusion, our study report the oncogenic role of JMJD3 in GC for the first time. JMJD3 might serve as an important epigenetic therapeutic target and/or prognostic predictor in GC.
Bioinspired magnetic nanoparticles as multimodal photoacoustic, photothermal and photomechanical contrast agents
Authors: Nima Zeid A. , Watanabe Fumiya , Jamshidi-Parsian Azemat , Sarimollaoglu Mustafa , Nedosekin Dmitry A. , Han Mikyung , Watts J. Alex , Biris Alexandru S. , Zharov Vladimir P. , Galanzha Ekaterina I.
Published: January 2019

Nanoparticles from magnetotactic bacteria have been used in conventional imaging, drug delivery, and magnetic manipulations. Here, we show that these natural nanoparticles and their bioinspired hybrids with near-infrared gold nanorods and folic acid can serve as molecular high-contrast photoacoustic probes for single-cell diagnostics and as photothermal agents for single-cell therapy using laser-induced vapor nanobubbles and magnetic field as significant signal and therapy amplifiers. These theranostics agents enable the detection and photomechanical killing of triple negative breast cancer cells that are resistant to conventional chemotherapy, with just one or a few low-energy laser pulses. In studies in vivo, we discovered that circulating tumor cells labeled with the nanohybrids generate transient ultrasharp photoacoustic resonances directly in the bloodstream as the basis for new super-resolution photoacoustic flow cytometry in vivo. These properties make natural and bioinspired magnetic nanoparticles promising biocompatible, multimodal, high-contrast, and clinically relevant cellular probes for many in vitro and in vivo biomedical applications.
Mitochondrial uncoupling has no effect on microvascular complications in type 2 diabetes
Authors: Hinder Lucy M. , Sas Kelli M. , O’Brien Phillipe D. , Backus Carey , Kayampilly Pradeep , Hayes John M. , Lin Cheng-mao , Zhang Hongyu , Shanmugam Sumathi , Rumora Amy E. , Abcouwer Steven F. , Brosius Frank C. , Pennathur Subramaniam , Feldman Eva L.
Published: January 2019

Diabetic peripheral neuropathy (DPN), diabetic kidney disease (DKD), and diabetic retinopathy (DR) contribute to significant morbidity and mortality in diabetes patients. The incidence of these complications is increasing with the diabetes epidemic, and current therapies minimally impact their pathogenesis in type 2 diabetes (T2D). Improved mechanistic understanding of each of the diabetic complications is needed in order to develop disease-modifying treatments for patients. We recently identified fundamental differences in mitochondrial responses of peripheral nerve, kidney, and retinal tissues to T2D in BKS-db/db mice. However, whether these mitochondrial adaptations are the cause or consequence of tissue dysfunction remains unclear. In the current study BKS-db/db mice were treated with the mitochondrial uncoupler, niclosamide ethanolamine (NEN), to determine the effects of mitochondrial uncoupling therapy on T2D, and the pathogenesis of DPN, DKD and DR. Here we report that NEN treatment from 6–24 wk of age had little effect on the development of T2D and diabetic complications. Our data suggest that globally targeting mitochondria with an uncoupling agent is unlikely to provide therapeutic benefit for DPN, DKD, or DR in T2D. These data also highlight the need for further insights into the role of tissue-specific metabolic reprogramming in the pathogenesis of diabetic complications.
γ-Glutamyltransferase enzyme activity of cancer cells modulates L-γ-glutamyl-p-nitroanilide (GPNA) cytotoxicity
Authors: Corti Alessandro , Dominici Silvia , Piaggi Simona , Belcastro Eugenia , Chiu Martina , Taurino Giuseppe , Pacini Simone , Bussolati Ovidio , Pompella Alfonso
Published: January 2019

L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine (Gln) transporter ASCT2, but recent studies have demonstrated that it is also able to inhibit other sodium-dependent and independent amino acid transporters. Moreover, GPNA is a well known substrate of the enzyme γ-glutamyltransferase (GGT). Our aim was to evaluate the effect of GGT-mediated GPNA catabolism on cell viability and Gln transport. The GGT-catalyzed hydrolysis of GPNA produced cytotoxic effects in lung cancer A549 cells, resulting from the release of metabolite p-nitroaniline (PNA) rather than from the inhibition of Gln uptake. Interestingly, compounds like valproic acid, verapamil and reversan were able to increase the cytotoxicity of GPNA and PNA, suggesting a key role of intracellular detoxification mechanisms. Our data indicate that the mechanism of action of GPNA is more complex than believed, and further confirm the poor specificity of GPNA as an inhibitor of Gln transport. Different factors may modulate the final effects of GPNA, ranging from GGT and ASCT2 expression to intracellular defenses against xenobiotics. Thus, other strategies - such as a genetic suppression of ASCT2 or the identification of new specific inhibitors - should be preferred when inhibition of ASCT2 function is required.
Imaging endogenous macrophage iron deposits reveals a metabolic biomarker of polarized tumor macrophage infiltration and response to CSF1R breast cancer immunotherapy
Authors: Leftin Avigdor , Ben-Chetrit Nir , Joyce Johanna A. , Koutcher Jason A.
Published: January 2019

Iron deposits are a phenotypic trait of tumor-associated macrophages (TAMs). Histological iron imaging and contrast-agent free magnetic resonance imaging (MRI) can detect these deposits, but their presence  in human cancer, and correlation with immunotherapeutic response is largely untested. Here, primarily using these iron imaging approaches, we evaluated the spatial distribution of polarized macrophage populations containing high endogenous levels of iron in preclinical murine models and human breast cancer, and used them as metabolic biomarkers to correlate TAM infiltration with response to immunotherapy in preclinical trials. Macrophage-targeted inhibition of the colony stimulating factor 1 receptor (CSF1R) by immunotherapy was confirmed to inhibit macrophage accumulation and slow mammary tumor growth in mouse models while also reducing hemosiderin iron-laden TAM accumulation as measured by both iron histology and in vivo iron MRI (FeMRI). Spatial profiling of TAM iron deposit infiltration defined regions of maximal accumulation and response to the CSF1R inhibitor, and revealed differences between microenvironments of human cancer according to levels of polarized macrophage iron accumulation in stromal margins. We therefore demonstrate that iron deposition serves as an endogenous metabolic imaging biomarker of TAM infiltration in breast cancer that has high translational potential for evaluation of immunotherapeutic response.
Frequency conversion of microwave signal without direct bias current using nanoscale magnetic tunnel junctions
Authors: Algarin J. M. , Ramaswamy B. , Weinberg I. N. , Chen Y. J. , Krivorotov I. N. , Katine J. A. , Shapiro B. , Waks E.
Published: January 2019

Frequency conversion forms an integral block of the electronic circuits used in various applications including energy harvesting, communications and signal processing. These frequency conversion units however require external power sources and occupy a large device footprint making it difficult to be integrated in micro-circuits. Here we demonstrate that nanoscale magnetic tunnel junctions can act as frequency converters without an external power supply or DC bias source. The device directly mixes an external microwave signal with the internal spin precession oscillations to create new frequencies tunable by an external magnetic field in a single device with a small device footprint. We observe up-conversion and down-conversion of the input signal for excitation frequencies between 2 GHz and 6 GHz. We also show that the device acts as a zero-bias rectifier that can generate voltages exceeding 12 mV when the excitation frequency matches the natural oscillations mode of the device.
Crabp2 Promotes Metastasis of Lung Cancer Cells via HuR and Integrin β1/FAK/ERK Signaling
Authors: Wu Jun-I , Lin Yi-Pei , Tseng Chien-Wei , Chen Hui-Jane , Wang Lu-Hai
Published: January 2019

Increased Crabp2 levels have been found in various types of cancer, and are associated with poor patients’ survival. Although Crabp2 is found to be overexpressed in lung cancer, its role in metastasis of lung cancer is unclear. In this study, Crabp2 was overexpressed in high-metastatic C10F4 than low-metastatic lung cancer cells. Analysis of clinical samples revealed that high CRABP2 levels were correlated with lymph node metastases, poor overall survival, and increased recurrence. Knockdown of Crabp2 decreased migration, invasion, anoikis resistance, andin vivometastasis. Crabp2 was co-immunoprecipitated with HuR, and overexpression of Crabp2 increased HuR levels, which promoted integrin β1/FAK/ERK signaling. Inhibition of HuR or integrin β1/FAK/ERK signaling reversed the promoting effect of Crabp2 in migration, invasion, and anoikis resistance. Knockdown of Crabp2 further inhibited the growth of cancer cells as compared with that by gemcitabine or irinotecan alone. The expression of Crabp2 in human lung tumors was correlated with stress marker CHOP. In conclusion, our findings have identified the promoting role of Crabp2 in anoikis resistance and metastasis. CRABP2 may serve as a prognostic marker and targeting CRABP2 may be exploited as a modality to reduce metastasis.
Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats
Authors: Stanisavljević Suzana , Čepić Aleksa , Bojić Svetlana , Veljović Katarina , Mihajlović Sanja , Đedović Neda , Jevtić Bojan , Momčilović Miljana , Lazarević Milica , Mostarica Stojković Marija , Miljković Đorđe , Golić Nataša
Published: January 2019

Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Mainly, Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportions of Clostridia and Bacilli classes were accompanied by an increase in Gamma-Proteobacteria in antibiotic-treated animals. Interestingly, a notable decrease in the Helicobacteraceae, Spirochaetaceae and Turicibacteriaceae was scored in antibiotic-treated groups. Also, levels of short chain fatty acids were reduced in the faeces of antibiotic-treated rats. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.
New insights into the coordination between the polymerization and 3′-5′ exonuclease activities in ϕ29 DNA polymerase
Authors: del Prado Alicia , Rodríguez Irene , Lázaro José María , Moreno-Morcillo María , de Vega Miguel , Salas Margarita
Published: January 2019

Bacteriophage ϕ29 DNA polymerase has two activities: DNA polymerization and 3′-5′ exonucleolysis governed by catalytic sites present in two structurally distant domains. These domains must work together to allow the correct replication of the template and to prevent the accumulation of errors in the newly synthesized DNA strand. ϕ29 DNA polymerase is endowed with a high processivity and strand displacement capacity together with a high fidelity. Previous studies of its crystallographic structure suggested possible interactions of residues of the exonuclease domain like the Gln180 with the fingers subdomain, or water mediated and direct hydrogen bond by the polar groups of residues Tyr101 and Thr189 that could stabilize DNA binding. To analyse their functional importance for the exonuclease activity of ϕ29 DNA polymerase we engineered mutations to encode amino acid substitutions. Our results confirm that both residues, Tyr101 and Thr189 are involved in the 3′-5′ exonuclease activity and in binding the dsDNA. In addition, Tyr101 is playing a role in processivity and Thr189 is an important determinant in the fidelity of the DNA polymerase. On the other hand, the biochemical characterization of the mutant derivatives of residue Gln180 showed how the mutations introduced enhanced the 3′-5′ exonuclease activity of the enzyme. A potential structural conformation prone to degrade the substrate is discussed.
X-ray structure of Fasciola hepatica Sigma class glutathione transferase 1 reveals a disulfide bond to support stability in gastro-intestinal environment
Authors: Line Kirsty , Isupov Michail N. , LaCourse E. James , Cutress David J. , Morphew Russell M. , Brophy Peter M. , Littlechild Jennifer A.
Published: January 2019

Sigma class GST (Prostaglandin D synthase), FhGST-S1, is present in the excretory–secretory products (ES) of the liver fluke parasite Fasciola hepatica as cargo of extracellular vesicles (EVs) released by the parasite. FhGST-S1 has a well characterised role in the modulation of the immune response; a key fluke intercession that allows for establishment and development within their hosts. We have resolved the three-dimensional structure of FhGST-S1 in complex with its co-factor glutathione, in complex with a glutathione-cysteine adduct, and in a glutathione disulfide complex in order to initiate a research pipeline to mechanistically understand how FhGST-S1 functions within the host environment and to rationally design selective inhibitors. The overall fold of FhGST-S1 shows high structural similarity to other Sigma class GSTs. However, a unique interdomain disulfide bond was found in the FhGST-S1 which could stabilise the structure within the host gastro-intestinal environment. The position of the two domains of the protein with respect to each other is seen to be crucial in the formation of the active site cleft of the enzyme. The interdomain disulfide bond raises the possibility of oxidative regulation of the active site of this GST protein.
Epidemiology, Patterns of treatment, and Mortality of Pediatric Trauma Patients in Japan
Authors: Aoki Makoto , Abe Toshikazu , Saitoh Daizoh , Oshima Kiyohiro
Published: January 2019

Limited information exists regarding the epidemiology, patterns of treatment, and mortality of pediatric trauma patients in Japan. To evaluate the characteristics and mortality of pediatric trauma patients in Japan, especially in traffic accidents. This was a retrospective cohort study between 2004 and 2015 from a nationwide trauma registry in Japan. Pediatric trauma patients divided into four age groups: <1 years; 1 ≤ 5 years; 6 ≤ 10 years; and 11 ≤ 15 years. Data on patients’ demographics, trauma mechanism and severity, treatments and in-hospital mortality were analyzed between the groups. There were 15,441 pediatric trauma patients during the study period. Among 15,441 pediatric patients, 779 belonged to the <1 year age group, 3,933 to the 1 ≤ 5 years age group, 5,545 to the 6 ≤ 10 age group, and 5,184 to the 11 ≤ 15 years age group. Male injuries (69%) were more frequent than female injuries. Head injuries (44%) were the most frequent and severe. Traffic accidents were the leading cause of trauma (44%). Overall in-hospital mortality was 3.9% and emergency department mortality was 1.4%. In-hospital mortality was 5.3%, 4.7%, 3.0% and 4.0% for the <1 year, 1 ≤ 5 years, 6 ≤ 10 years, and 11 ≤ 15 years age groups respectively. A total of 57% of all trauma deaths were before or upon arrival at hospital. Traffic accidents for the <1 year age group was the highest category of mortality (15%). The overall in-hospital mortality of Japanese pediatric trauma patients was 3.9% based on the nationwide trauma registry of Japan. The main cause of severe trauma was traffic accidents, especially in patients <1 year of age whose mortality was 15%.
Integration of facial features under memory load
Authors: Ölander K. , Muukkonen I. , Saarela T. P. , Salmela V. R.
Published: January 2019

Simple visual items and complex real-world objects are stored into visual working memory as a collection of independent features, not as whole or integrated objects. Storing faces into memory might differ, however, since previous studies have reported perceptual and memory advantage for whole faces compared to other objects. We investigated whether facial features can be integrated in a statistically optimal fashion and whether memory maintenance disrupts this integration. The observers adjusted a probe – either a whole face or isolated features (eyes or mouth region) – to match the identity of a target while viewing both stimuli simultaneously or after a 1.5 second retention period. Precision was better for the whole face compared to the isolated features. Perceptual precision was higher than memory precision, as expected, and memory precision further declined as the number of memorized items was increased from one to four. Interestingly, the whole-face precision was better predicted by models assuming injection of memory noise followed by integration of features than by models assuming integration of features followed by the memory noise. The results suggest equally weighted or optimal integration of facial features and indicate that feature information is preserved in visual working memory while remembering faces.
Using host species traits to understand the Wolbachia infection distribution across terrestrial beetles
Authors: Kajtoch Łukasz , Kolasa Michał , Kubisz Daniel , Gutowski Jerzy M. , Ścibior Radosław , Mazur Miłosz A. , Holecová Milada
Published: January 2019

Knowledge of Wolbachia prevalence with respect to its hosts is restricted mainly to taxonomic/phylogenetic context. In contrast, relations between infection and most host’s ecological and biological traits are poorly understood. This study aimed to elaborate on relations between bacteria and its beetle hosts in taxonomic and the ecological contexts. In particular, the goal is to verify which ecological and biological traits of beetles could cause them to be prone to be infected. Verification of Wolbachia infection status across 297 beetle taxa showed that approximately 27% of taxa are infected by supergroups A and B. Only minor support for coevolution between bacteria and its beetle hosts was observed in some genera of beetles, but in general coevolution between beetles and Wolbachia was rejected. Some traits of beetles were found to be unrelated to Wolbachia prevalence (type of range and thermal preferences); some traits were related with ambiguous effects (habitats, distribution, mobility and body size); some were substantially related (reproduction mode and trophy). The aforementioned summary does not show obvious patterns of Wolbachia prevalence and diversity in relation to host taxonomy, biology, and ecology. As both Wolbachia and Coleoptera are diverse groups, this lack of clear patterns is probably a reflection of nature, which is characterised by highly diversified and probably unstable relations.
Ambient Aqueous-Phase Synthesis of Copper Nanoparticles and Nanopastes with Low-Temperature Sintering and Ultra-High Bonding Abilities
Authors: Kamikoriyama Yoichi , Imamura Hiroshi , Muramatsu Atsushi , Kanie Kiyoshi
Published: January 2019

Copper nanoparticles (NPs) with an average particle diameter of 50–60 nm were successfully obtained by reducing an aqueous solution of a copper(II)-nitrilotriacetic acid complex with an aqueous hydrazine solution at room temperature under an air atmosphere. Copper NP-based nanopastes were printed onto a glass substrate using a metal screen mask and pressureless sintered under a nitrogen atmosphere at 200 °C for 30 min. The electrical resistivity of the resulting copper electrode was 16 μΩ · cm. For a metal-to-metal bonding test, copper nanopaste was printed on an oxygen-free copper plate, another oxygen-free copper plate was placed on top, and the bonding strength between the copper plates when pressureless sintered under a nitrogen atmosphere at 200 °C for 30 min was 39 MPa. TEM observations confirmed that highly crystalline metal bonding occurred between the copper NPs and the copper plate to introduce the ultrahigh strength. The developed copper NPs could provide promising advances as nanopastes for sustainable fabrication of copper electrodes and die attachment materials for the production of next-generation power semiconductors.
Mechanism of substrate-induced anisotropic growth of monolayer WS2 by kinetic Monte Carlo simulations
Authors: Wu Lixiang , Yang Weihuang , Wang Gaofeng
Published: January 2019

Controlled anisotropic growth of two-dimensional materials provides an approach for the synthesis of large single crystals and nanoribbons, which are promising for applications as low-dimensional semiconductors and in next-generation optoelectronic devices. In particular, the anisotropic growth of transition metal dichalcogenides induced by the substrate is of great interest due to its operability. To date, however, their substrate-induced anisotropic growth is typically driven by the optimization of experimental parameters without uncovering the fundamental mechanism. Here, the anisotropic growth of monolayer tungsten disulfide on an ST-X quartz substrate is achieved by chemical vapor deposition, and the mechanism of substrate-induced anisotropic growth is examined by kinetic Monte Carlo simulations. Results show that, besides the variation of substrate adsorption, the chalcogen to metal (C/M) ratio is a major contributor to the large growth anisotropy and the polarization of undergrowth and overgrowth; either perfect isotropy or high anisotropy can be expected when the C/M ratio equals 2.0 by properly controlling the linear relationship between gas flux and temperature.
Qresp, a tool for curating, discovering and exploring reproducible scientific papers
Authors: Govoni Marco , Munakami Milson , Tanikanti Aditya , Skone Jonathan H. , Runesha Hakizumwami B. , Giberti Federico , de Pablo Juan , Galli Giulia
Published: January 2019

We propose a strategy and present a simple tool to facilitate scientific data reproducibility by making available, in a distributed manner, all data and procedures presented in scientific papers, together with metadata to render them searchable and discoverable. In particular, we describe a graphical user interface (GUI), Qresp, to curate papers (i.e. generate metadata) and to explore curated papers and automatically access the data presented in scientific publications.
Integrating 3D cell culture of PC12 cells with microchip-based electrochemical detection
Authors: Mehl Benjamin T. , Martin R. Scott
Published: January 2019

We describe a microfluidic system that utilizes 3D printing and 3D culture scaffolds that can also be integrated with microchip-based analysis technologies.
Do biomedical engineers dream of graphene sheets?
Authors: Girão André F. , Serrano María C. , Completo António , Marques Paula A. A. P.
Published: January 2019

Graphene based-materials are leading a biomedical revolution towards the materialization of approaches so far within the reach of science fiction.
In situ reduction and exfoliation of g-C3N4 nanosheets with copious active sites via a thermal approach for effective water splitting
Authors: Pawar Rajendra C. , Kang Suhee , Han Hyuksu , Choi Heechae , Lee Caroline S.
Published: January 2019

Poor optical absorbance and charge recombination are the major drawbacks of polymeric graphitic carbon nitride (g-C3N4)-based photocatalysts.
Highly tunable periodic imidazole-based mesoporous polymers as cooperative catalysts for efficient carbon dioxide fixation
Authors: Zhang Wei , Mei Yu , Wu Peng , Wu Hai-Hong , He Ming-Yuan
Published: January 2019

We designed new periodic imidazole-based mesoporous polymers for cooperative catalysis, revealing the structure–activity relationships in CO2 cycloaddition.
Isotopic evidence of nitrate sources and its transformations in a human-impacted watershed
Authors: Ding Jingtao , Xi Beidou , Xu Qigong , Meng Haibo , Shen Yujun , Cheng Hongsheng
Published: January 2019

The considerable spatial and temporal variabilities of nitrogen (N) processing introduce large uncertainties for quantifying N cycles on a large scale, particularly in plain river network regions with complicated hydrographic connections and mixed multiple N sources.
Towards the high-throughput synthesis of bulk materials: thermoelectric PbTe–PbSe–SnTe–SnSe alloys
Authors: Ortiz Brenden R. , Adamczyk Jesse M. , Gordiz Kiarash , Braden Tara , Toberer Eric S.
Published: January 2019

Despite extensive research, much of PbSnTeSe alloying space is unexplored. High-throughput bulk synthesis augments literature with high-resolution (121 sample) property maps.
Ion specific, odd–even glass transition temperatures and conductivities in precise network polymerized ionic liquids
Authors: Shen Chengtian , Zhao Qiujie , Evans Christopher M.
Published: January 2019

Network architectures reveal odd–even effects in existing PIL systems.
An Ising transition of chessboard tilings in a honeycomb liquid crystal
Authors: Fall William S. , Nürnberger Constance , Zeng Xiangbing , Liu Feng , Kearney Stephen J. , Gehring Gillian A. , Tschierske Carsten , Ungar Goran
Published: January 2019

Rod-like molecules with two disparate side-chains self-assemble as square honeycomb undergoing a demixing Ising-type transition from single-coloured to two-coloured tiling.
Ni nanoparticle supported reduced graphene oxide as a highly active and durable heterogeneous material for coupling reactions
Authors: Rana Surjyakanta , Varadwaj G. Bishwa Bidita , Jonnalagadda S. B.
Published: January 2019

Ni nanoparticle supported reduced graphene oxide is shown to be a highly active and durable heterogeneous catalyst for Kumada–Corriu cross-coupling reactions.
DNA-templated Au nanoclusters coupled with proximity-dependent hybridization and guanine-rich DNA induced quenching: a sensitive fluorescent biosensing platform for DNA detection
Authors: Wang Hai-Bo , Bai Hong-Yu , Dong Gao-Li , Liu Yan-Ming
Published: January 2019

A fluorescent biosensing platform has been developed for the sensitive detection of DNA based on poly(A) DNA-templated AuNCs and G-rich DNA proximity-induced quenching.
A large-scale, ultrahigh-resolution nanoemitter ordered array with PL brightness enhanced by PEALD-grown AlN coating
Authors: Peng Mingzeng , Zheng Xinhe , Liu Sanjie , Wei Huiyun , He Yingfeng , Li Meiling , An Yunlai , Song Yimeng , Qiu Peng
Published: January 2019

A high-brightness III-nitride nanoemitter array was achieved with an ultrahigh resolution of 31 750 dpi for smart displays, advanced optical imaging, big-data optical information, and micro/nano opto-electro-mechanical systems.
Direct covalent modification of black phosphorus quantum dots with conjugated polymers for information storage
Authors: Cao Yaming , Zhang Bin , Tian Xiangyu , Gu Minchao , Chen Yu
Published: January 2019

By using a one-step synthetic strategy, the first conjugated polymer covalently functionalized BPQDs have been synthesized. This material exhibits an excellent nonvolatile rewritable memory effect, with a large ON/OFF current ratio (>107) and a low switch-on voltage (−0.89 V).
Nonlayered tellurene as an elemental 2D topological insulator: experimental evidence from scanning tunneling spectroscopy
Authors: Khatun Salma , Banerjee Arnab , Pal Amlan J.
Published: January 2019

In alpha-tellurene, elemental topological insulator behavior along with an extended metallic edge opening monotonically into gapped states has been evidenced.
Reactive block copolymers for patterned surface immobilization with sub-30 nm spacing
Authors: Turgut Hatice , Dingenouts Nico , Trouillet Vanessa , Krolla-Sidenstein Peter , Gliemann Hartmut , Delaittre Guillaume
Published: January 2019

Reactive polystyrene-block-polyisoprene copolymers are synthesized by nitroxide-mediated polymerization, self-assemble within ultra-thin films, and exhibit surface reactivity for patterned immobilization.