bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antifungal and anti-biofilm activity of the first cryptic antimicrobial peptide from an archaeal protein against Candida spp. clinical isolates
Authors: Roscetto Emanuela , Contursi Patrizia , Vollaro Adriana , Fusco Salvatore , Notomista Eugenio , Catania Maria Rosaria 
Published: November 2018

AbstractCandida species cause cutaneous and systemic infections with a high mortality rate, especially in immunocompromised patients. The emergence of resistance to the most common antifungal drugs, also due to biofilm formation, requires the development of alternative antifungal agents. The antimicrobial peptide VLL-28, isolated from an archaeal transcription factor, shows comparable antifungal activity against 10 clinical isolates of Candida spp. Using a fluoresceinated derivative of this peptide, we found that VLL-28 binds to the surface of planktonic cells. This observation suggested that it could exert its antifungal activity by damaging the cell wall. In addition, analyses performed on biofilms via confocal microscopy revealed that VLL-28 is differentially active on all the strains tested, with C. albicans and C. parapsilosis being the most sensitive ones. Notably, VLL-28 is the first example of an archaeal antimicrobial peptide that is active towards Candida spp. Thus, this points to archaeal microorganisms as a possible reservoir of novel antifungal agents.
Microbial diversity and biosignatures of amorphous silica deposits in orthoquartzite caves
Authors: Sauro Francesco , Cappelletti Martina , Ghezzi Daniele , Columbu Andrea , Hong Pei-Ying , Zowawi Hosam Mamoon , Carbone Cristina , Piccini Leonardo , Vergara Freddy , Zannoni Davide , De Waele Jo 
Published: November 2018

AbstractChemical mobility of crystalline and amorphous SiO2 plays a fundamental role in several geochemical and biological processes, with silicate minerals being the most abundant components of the Earth’s crust. Although the oldest evidences of life on Earth are fossilized in microcrystalline silica deposits, little is known about the functional role that bacteria can exert on silica mobility at non-thermal and neutral pH conditions. Here, a microbial influence on silica mobilization event occurring in the Earth’s largest orthoquartzite cave is described. Transition from the pristine orthoquartzite to amorphous silica opaline precipitates in the form of stromatolite-like structures is documented through mineralogical, microscopic and geochemical analyses showing an increase of metals and other bioessential elements accompanied by permineralized bacterial cells and ultrastructures. Illumina sequencing of the 16S rRNA gene describes the bacterial diversity characterizing the consecutive amorphization steps to provide clues on the biogeochemical factors playing a role in the silica solubilization and precipitation processes. These results show that both quartz weathering and silica mobility are affected by chemotrophic bacterial communities, providing insights for the understanding of the silica cycle in the subsurface.
Sorption of ammonium and nitrate to biochars is electrostatic and pH-dependent
Authors: Fidel Rivka B. , Laird David A. , Spokas Kurt A. 
Published: November 2018

AbstractBiochars are potentially effective sorbents for NH4+ and NO3− in water treatment and soil applications. Here we compare NH4+ and NO3− sorption rates to acid-washed biochars produced from red oak (Quercus rubra) and corn stover (Zea mays) at three pyrolysis temperatures (400, 500 and 600 °C) and a range of solution pHs (3.5–7.5). Additionally, we examined sorption mechanisms by quantification of NH4+ and NO3− sorption, as well as Ca2+ and Cl− displacement for corn stover biochars. Solution pH curves showed that NH4+ sorption was maximized (0.7–0.8 mg N g−1) with low pyrolysis temperature (400 °C) biochar at near neutral pH (7.0–7.5), whereas NO3− sorption was maximized (1.4–1.5 mg N g−1) with high pyrolysis temperatures (600 °C) and low pH (3.5–4). The Langmuir (r2 = 0.90–1.00) and Freundlich (r2 = 0.81–0.97) models were good predictors for both NH4+ (pH 7) and NO3− (pH 3.7) sorption isotherms. Lastly, NH4+ and NO3− displaced Ca2+ and Cl−, respectively, from previously CaCl2-saturated corn stover biochars. Results from the pH curves, Langmuir isotherms, and cation displacement curves all support the predominance of ion exchange mechanisms. Our results demonstrate the importance of solution pH and chemical composition in influencing NH4+ and NO3− sorption capacities of biochar.
Shared genetic aetiology between cognitive performance and brain activations in language and math tasks
Authors: Le Guen Yann , Amalric Marie , Pinel Philippe , Pallier Christophe , Frouin Vincent 
Published: November 2018

AbstractCognitive performance is highly heritable. However, little is known about common genetic influences on cognitive ability and brain activation when engaged in a cognitive task. The Human Connectome Project (HCP) offers a unique opportunity to study this shared genetic etiology with an extended pedigree of 785 individuals. To investigate this common genetic origin, we took advantage of the HCP dataset, which includes both language and mathematics activation tasks. Using the HCP multimodal parcellation, we identified areals in which inter-individual functional MRI (fMRI) activation variance was significantly explained by genetics. Then, we performed bivariate genetic analyses between the neural activations and behavioral scores, corresponding to the fMRI task accuracies, fluid intelligence, working memory and language performance. We observed that several parts of the language network along the superior temporal sulcus, as well as the angular gyrus belonging to the math processing network, are significantly genetically correlated with these indicators of cognitive performance. This shared genetic etiology provides insights into the brain areas where the human-specific genetic repertoire is expressed. Studying the association of polygenic risk scores, using variants associated with human cognitive ability and brain activation, would provide an opportunity to better understand where these variants are influential.
Ancient DNA of Phoenician remains indicates discontinuity in the settlement history of Ibiza
Authors: Zalloua Pierre , Collins Catherine J. , Gosling Anna , Biagini Simone Andrea , Costa Benjamí , Kardailsky Olga , Nigro Lorenzo , Khalil Wissam , Calafell Francesc , Matisoo-Smith Elizabeth 
Published: November 2018

AbstractIbiza was permanently settled around the 7th century BCE by founders arriving from west Phoenicia. The founding population grew significantly and reached its height during the 4th century BCE. We obtained nine complete mitochondrial genomes from skeletal remains from two Punic necropoli in Ibiza and a Bronze Age site from Formentara. We also obtained low coverage (0.47X average depth) of the genome of one individual, directly dated to 361–178 cal BCE, from the Cas Molí site on Ibiza. We analysed and compared ancient DNA results with 18 new mitochondrial genomes from modern Ibizans to determine the ancestry of the founders of Ibiza. The mitochondrial results indicate a predominantly recent European maternal ancestry for the current Ibizan population while the whole genome data suggest a significant Eastern Mediterranean component. Our mitochondrial results suggest a genetic discontinuity between the early Phoenician settlers and the island’s modern inhabitants. Our data, while limited, suggest that the Eastern or North African influence in the Punic population of Ibiza was primarily male dominated.
A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer’s disease mouse model
Authors: Campagna Jesus , Spilman Patricia , Jagodzinska Barbara , Bai Dongsheng , Hatami Asa , Zhu Chunni , Bilousova Tina , Jun Michael , Elias Chris Jean , Pham Johnny , Cole Gregory , LaDu Mary Jo , Jung Michael E. , Bredesen Dale E. , John Varghese 
Published: November 2018

AbstractWe describe here the results from the testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases the levels of the neuroprotective enzyme SirT1 while not affecting levels of neurotoxic sirtuin 2 (SirT2) in vitro in ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable and brain penetrant. In vivo, A03 treatment increased SirT1 levels in the hippocampus of 5XFAD-ApoE4 (E4FAD) Alzheimer’s disease (AD) model mice and elicited cognitive improvement while inducing no observed toxicity. We were able to resolve the enantiomers of A03 and show using in vitro models that the L-enantiomer was more potent than the corresponding D-enantiomer in increasing SirT1 levels. ApoE4 expression has been shown to decrease the level of the NAD-dependent deacetylase and major longevity determinant SirT1 in brain tissue and serum of AD patients as compared to normal controls. A deficiency in SirT1 level has been recently implicated in increased tau acetylation, a dominant post-translational modification and key pathological event in AD and tauopathies. Therefore, as a novel approach to therapeutic development for AD, we targeted identification of compounds that enhance and normalize brain SirT1 levels.
Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease
Authors: Mahmoudi Mahdi , Ashraf-Ganjouei Amir , Javinani Ali , Shahram Farhad , Meguro Akira , Mizuki Nobuhisa , Ahmadzadeh Nooshin , Jafarinejad-Farsangi Saeideh , Mostafaei Shayan , Kavosi Hoda , Faezi Seyedeh Tahereh , Akhlaghi Maassoumeh , Davatchi Fereydoun 
Published: November 2018

AbstractBehçet’s Disease (BD) pathogenesis remains unclear, but some genetic loci and environmental factors are proposed to play a role. Here, we investigate the association of the endoplasmic reticulum aminopeptidase-1 (ERAP1) gene variants and HLA-B*51 with BD susceptibility and clinical manifestations in Iranian patients. In the study, 748 BD patients and 776 healthy individuals were included. The MGB-TaqMan Allelic Discrimination method was used to genotype 10 common missense single nucleotide polymorphisms (SNPs) and one intronic SNP in the ERAP1 gene region. We found no significant association between the 11 SNPs and BD in allelic and genotypic association tests. However, rs30187 showed the strongest association with BD in the recessive genotype model of the risk T allele in HLA-B*51 carriers. Although this became insignificant after correcting for multiple comparisons, the homozygous rs30187 risk allele genotype (TT) increased disease susceptibility in HLA-B*51 carriers in epistasis analysis, and the rs30187 TT recessive genotype showed a significant association with risk of cardiac involvement in the all patients and articular involvements in HLA-B*51 positive patients. Our findings suggest that gene-gene interactions between HLA-B*51 and ERAP1 variants is important for BD development, however, ERAP1 variants which interact with HLA-B*51 may differ among disease phenotypes or populations.
BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells
Authors: Mahauad-Fernandez Wadie D. , Naushad Wasifa , Panzner Tyler D. , Bashir Amani , Lal Geeta , Okeoma Chioma M. 
Published: November 2018

AbstractBone marrow stromal antigen 2 (BST-2) mediates various facets of cancer progression and metastasis. Here, we show that BST-2 is linked to poor survival in invasive breast cancer patients as its expression positively correlates with disease severity. However, the mechanisms that drive the pro‐metastatic functions of BST-2 are not fully understood. Correlation of BST-2 expression and tumor aggressiveness was analyzed in human tissue samples. Migration, invasion, and competitive experimental metastasis assays were used to measure the cellular responses after silencing BST-2 expression. Using a mouse model of breast cancer, we show that BST-2 promotes metastasis independent of the primary tumor. Additional experiments show that suppression of BST-2 renders non-adherent cancer cells non-viable by sensitizing cells to anoikis. Embedment of cancer cells in basement membrane matrix reveals that silencing BTS-2 expression inhibits invadopodia formation, extracellular matrix degradation, and subsequent cell invasion. Competitive experimental pulmonary metastasis shows that silencing BST-2 reduces the numbers of viable circulating tumor cells (CTCs) and decreases the efficiency of lung colonization. Our data define a previously unknown function for BST-2 in the i) formation of invadopodia, ii) degradation of extracellular matrix, and iii) protection of CTCs from hemodynamic stress. We believe that physical (tractional forces) and biochemical (ECM type/composition) cues may control BST-2’s role in cell survival and invadopodia formation. Collectively, our findings highlight BST-2 as a key factor that allows cancer cells to invade, survive in circulation, and at the metastatic site.
Multiple genetic mutations caused by NKX6.3 depletion contribute to gastric tumorigenesis
Authors: Yoon Jung Hwan , Kim Olga , Eun Jung Woo , Choi Sung Sook , Ashktorab Hassan , Smoot Duane T. , Nam Suk Woo , Park Won Sang 
Published: November 2018

AbstractNKX family members are involved in a variety of developmental processes such as cell fate determination in the central nervous system, gastrointestinal tract, and pancreas. However, whether NKX6.3 contributes to gastric carcinogenesis remains unclear. The objective of this study was to examine roles of NKX6.3 depletion in mutagenesis and gastric carcinogenesis, focusing on its effects on genetic alterations and expression of genes. Our results revealed that NKX6.3 depletion induced multiple genetic mutations in coding regions, including high frequency of point mutations such as cytosine-to-thymine and guanine-to-adenine transitions caused by aberrant expression of AICDA/APOBEC family in human gastric epithelial cells. Interestingly, NKX6.3 downregulated AICDA/APOBEC family, NFκB, and CBFβ genes by acting as a transcription factor while inhibiting deaminase activity in gastric epithelial cells. Functional relevance of NKX6.3 was validated in xenograft mice injected with NKX6.3 depleting cells. NKX6.3 depletion resulted in tumor formation and mutations of tumor-associated genes, including p53 and E-cadherin. Moreover, expression levels of NKX6.3 and its target genes were analyzed in tumors derived from mice implanted with NKX6.3 depleting cells and tissue samples of gastric cancer patients. Our results indicate that NKX6.3 depletion in gastric epithelial cells activates AICDA/APOBEC family, leading to accumulation of genetic mutations and eventually driving the development of gastric cancers.
Predictability of the impact of multiple stressors on the keystone species Daphnia
Authors: Cuenca Cambronero Maria , Marshall Hollie , De Meester Luc , Davidson Thomas Alexander , Beckerman Andrew P. , Orsini Luisa 
Published: November 2018

AbstractEutrophication and climate change are two of the most pressing environmental issues affecting up to 50% of aquatic ecosystems worldwide. Mitigation strategies to reduce the impact of environmental change are complicated by inherent difficulties of predicting the long-term impact of multiple stressors on natural populations. Here, we investigated the impact of temperature, food levels and carbamate insecticides, in isolation and in combination, on current and historical populations of the freshwater grazer Daphnia. We used common garden and competition experiments on historical and modern populations of D. magna ‘resurrected’ from a lake with known history of anthropogenic eutrophication and documented increase in ambient temperature over time. We found that these populations response dramatically differed between single and multiple stressors. Whereas warming alone induced similar responses among populations, warming combined with insecticides or food limitation resulted in significantly lower fitness in the population historically exposed to pesticides. These results suggest that the negative effect of historical pesticide exposure is magnified in the presence of warming, supporting the hypothesis of synergism between chemical pollution and other stressors.
Identification of 55,000 Replicated DNA Methylation QTL
Authors: McRae Allan F. , Marioni Riccardo E. , Shah Sonia , Yang Jian , Powell Joseph E. , Harris Sarah E. , Gibson Jude , Henders Anjali K. , Bowdler Lisa , Painter Jodie N. , Murphy Lee , Martin Nicholas G. , Starr John M. , Wray Naomi R. , Deary Ian J. , Visscher Peter M. , Montgomery Grant W. 
Published: November 2018

AbstractDNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is a potential candidate for explaining the many identified SNP associations with disease that are not found in coding regions. We replicated 52,916 cis and 2,025 trans DNA methylation quantitative trait loci (mQTL) using methylation from whole blood measured on Illumina HumanMethylation450 arrays in the Brisbane Systems Genetics Study (n = 614 from 177 families) and the Lothian Birth Cohorts of 1921 and 1936 (combined n = 1366). The trans mQTL SNPs were found to be over-represented in 1 Mbp subtelomeric regions, and on chromosomes 16 and 19. There was a significant increase in trans mQTL DNA methylation sites in upstream and 5′ UTR regions. The genetic heritability of a number of complex traits and diseases was partitioned into components due to mQTL and the remainder of the genome. Significant enrichment was observed for height (p = 2.1 × 10−10), ulcerative colitis (p = 2 × 10−5), Crohn’s disease (p = 6 × 10−8) and coronary artery disease (p = 5.5 × 10−6) when compared to a random sample of SNPs with matched minor allele frequency, although this enrichment is explained by the genomic location of the mQTL SNPs.
Sero-prevalence of Helicobacter pylori CagA immunoglobulin G antibody, serum pepsinogens and haemoglobin levels in adults
Authors: Muhsen Khitam , Sinnreich Ronit , Beer-Davidson Gany , Nassar Hisham , Cohen Daniel , Kark Jeremy D. 
Published: November 2018

AbstractAssociations observed of Helicobacter pylori infection with haemoglobin levels are inconsistent. We examined associations of H. pylori sero-prevalence and serum pepsinogens (PGs), as non-invasive markers of atrophic gastritis, with haemoglobin levels. A cross-sectional study was undertaken among 654 Jewish and 937 Arab residents of Jerusalem, aged 25–78 years, randomly selected from Israel’s national population registry in age-sex and population strata. Sera were tested for H. pylori IgG, cytotoxin–associated gene A (CagA) antigen IgG antibody and PGs levels. Multivariable models were fitted to account for confounders. Participants with atrophic gastritis (PGI < 30 μg/L or a PGI: PGII < 3.0) had lower haemoglobin levels than those without: beta-coefficient −0.34 (95% CI −0.59, −0.09); in men −0.27 (95% CI −0.67, 0.12), and in women −0.43 (95% CI −0.74, −0.12). Lower haemoglobin levels were noted in persons with CagA antibody than in those H. pylori sero-negative or H. pylori-CagA sero-negative: beta-coefficient −0.14 (95% CI −0.29, 0.01). Anaemia was more common among women and men with than without atrophic gastritis: adjusted OR 2.58 (95% CI 1.48, 4.48) and 1.52 (95% CI 0.59, 3.95), respectively. In conclusion, independent of known correlates, atrophic gastritis and apparently CagA sero-positivity, a marker of H. pylori virulent strains, are associated with lower haemoglobin levels.
Role of the Ebola membrane in the protection conferred by the three-mAb cocktail MIL77
Authors: Cao Ping , Bai Haihong , Wang Xinghe , Che Jinjing 
Published: November 2018

AbstractMIL77, which has a higher manufacturing capacity than ZMapp, comprises MIL77-1, MIL77-2, and MIL77-3. The mechanisms by which these antibodies inhibit glycoprotein are unclear. Infection by viruses with lipid-bilayer envelopes occurs via the fusion of the viral membrane with the membrane of the target cell. Therefore, the interaction between the antibodies and the EBOV membrane is crucial. We examined the interactions between MIL77 and the viral membrane using SPR. MIL77-1 selectively binds to viral membranes, while MIL77-2 and MIL77-3 do not. MIL77-1’s ability to screen the more rigid domains of the membranes results in a locally increased concentration of the drug at the fusion site. Although MIL77-2 recognizes an epitope of GP, it is not necessary in the MIL77 cocktail. These results highlight the importance of EBOV membrane interactions in improving the efficiency of a neutralizing antibody. Furthermore, the viral membrane may be an important target of antibodies against EBOV.
Extracellular vesicles produced in B cells deliver tumor suppressor miR-335 to breast cancer cells disrupting oncogenic programming in vitro and in vivo
Authors: Almanza Gonzalo , Rodvold Jeffrey J. , Tsui Brian , Jepsen Kristen , Carter Hannah , Zanetti Maurizio 
Published: November 2018

AbstractThe successful implementation of miRNA (miR) therapies in humans will ultimately rely on the use of vehicles with improved cellular delivery capability. Here we tested a new system that leverages extracellular vesicles (EVs) laden with a tumor suppressor miRNA (miR-335) produced in B cells by plasmid DNA induction (iEVs). We demonstrate that iEVs-335 efficiently and durably restored the endogenous miR-335 pool in human triple negative breast cancer cells, downregulated the expression of the miR-335 target gene SOX4 transcription factor, and markedly inhibited tumor growth in vivo. Remarkably, iEVs-335 mediated transcriptional effects that persisted in tumors after 60 days post orthotopic implantation. Genome-wide RNASeq analysis of cancer cells treated in vitro with iEVs-335 showed the regulation of a discrete number of genes only, without broad transcriptome perturbations. This new technology may be ideally suited for therapies aimed to restore tumor suppressor miRNAs in cancer cells, disrupting the oncogenic program established after escape from miRNA control.
Green preparation and characterization of graphene oxide/carbon nanotubes-loaded carboxymethyl cellulose nanocomposites
Authors: Son Yeong-Rae , Park Soo-Jin 
Published: November 2018

AbstractIn this study, a homogeneous and stable dispersion of graphene oxide (GO)/carbon nanotube (CNT) complexes (GCCs) was obtained by dispersing CNTs in an aqueous solution using GO in the absence of dispersing agents. Furthermore, carboxymethyl cellulose/GCC (CMC/GCC) nanocomposite films were prepared by a simple solution mixing-evaporation method. The dispersibility of the GCCs with different CNT contents was investigated by UV-Vis spectrophotometry. The morphological and crystalline structures of the samples were analyzed by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy were conducted to identify the chemical composition of GO, CNTs, and GCCs. These results revealed that CNTs could be stably dispersed in water using GO. In addition, when CMC/GCC nanocomposite films were prepared by mixing CMC and GCCs, CNTs were uniformly dispersed in the CMC matrix. The tensile behavior was investigated using a universal testing machine. The tensile strength and Young’s modulus of the CMC/GCC nanocomposite films were significantly improved by up to about 121% and 122%, respectively, compared to those of pure CMC because of uniform and strong π-π interfacial interactions between CNTs and CMC polymer.