bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractMatrix 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

AbstractTuberous 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

AbstractAcute 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

AbstractMelamine, 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

AbstractGenome 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

AbstractHelical 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

AbstractBecause 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

AbstractProcellariiform 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

AbstractThe 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

AbstractHistone 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

AbstractNanoparticles 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

AbstractDiabetic 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

AbstractL-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.