bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forfeiting the priority effect: turnover defines biofilm community succession
Authors: Brislawn Colin J , Graham Emily B , Dana Karl , Ihardt Peter , Fansler Sarah J , Chrisler William B , Cliff John B , Stegen James C , Moran James J , Bernstein Hans C 
Published: March 2019

Abstract
Microbial community succession is a fundamental process that affects underlying functions of almost all ecosystems; yet the roles and fates of the most abundant colonizers are often poorly understood. Does early abundance spur long term persistence? How do deterministic and stochastic processes influence the ecological contribution of colonizers? We performed a succession experiment within a hypersaline ecosystem to investigate how different processes contributed to the turnover of founder species. Bacterial and eukaryotic colonizers were identified during primary succession and tracked through a defined, 79-day biofilm maturation period using 16S and 18S rRNA gene sequencing in combination with high resolution imaging that utilized stable isotope tracers to evaluate successional patterns of primary producers and nitrogen fixers. The majority of the founder species did not maintain high abundance throughout succession. Species replacement (versus loss) was the dominant process shaping community succession. We also asked if different ecological processes acted on bacteria versus Eukaryotes during succession and found deterministic and stochastic forces corresponded more with microeukaryote and bacterial colonization, respectively. Our results show that taxa and functions belonging to different kingdoms, which share habitat in the tight spatial confines of a biofilm, were influenced by different ecological processes and time scales of succession.
Pilot study of DNA methylation, molecular aging markers and measures of health and well-being in aging
Authors: Vyas Chirag M. , Hazra Aditi , Chang Shun-Chiao , Qiu Weiliang , Reynolds Charles F. , Mischoulon David , Chang Grace , Manson JoAnn E. , De Vivo Immaculata , Okereke Olivia I. 
Published: March 2019

AbstractRelations of DNA methylation markers to other biological aging markers and to psychosocial, behavioral, and health measures remain unclear. The sample included 23 participants (n = 11 cases with psychiatric diagnoses andn = 12 controls without current or lifetime psychiatric disorder), balanced by age and sex. Genomic DNA was extracted from blood samples; the following were performed: genome-wide DNA methylation assay using Illumina 850k methylationEPIC; PCR assays for relative telomere length (RTL) and mitochondrial DNA copy number (mtCN). Exposures were: case status; depression and anxiety symptoms; psychosocial support; subjective and objective cognition. Outcomes were: DNA methylation age (DNAm age); RTL; mtCN; extrinsic and intrinsic epigenetic age acceleration (EEAA and IEAA). Stronger correlation with chronological age was observed for DNAm age (ρ = 0.86;p < 0.0001) compared to RTL (ρ = −0.53;p < 0.01); mtCN was not correlated with age. DNAm age was more strongly correlated with behavioral and health variables than RTL or mtCN; e.g., correlations with DNAm age: body mass index (ρ = 0.36;p = 0.10); smoking pack-years (ρ = 0.37;p = 0.08); physical activity (ρ = −0.56;p = 0.01); alcohol intake (ρ = 0.56;p = 0.01). DNAm age was inversely correlated with psychosocial support (ρ = −0.42;p = 0.048) and Modified Mini-Mental State score (ρ = −0.44;p = 0.01). Anxiety, psychosocial support, and objective cognition were significantly related to accelerated aging; depression and subjective cognition were not. In conclusion, DNAm age correlated more strongly with chronological age and key psychosocial, behavioral, and health variables than RTL or mtCN. Signals for associations with epigenetic aging were observed for psychosocial and neurobehavioral variables.
Akirin2 is modulated by miR-490-3p and facilitates angiogenesis in cholangiocarcinoma through the IL-6/STAT3/VEGFA signaling pathway
Authors: Leng Kaiming , Xu Yi , Kang Pengcheng , Qin Wei , Cai Hailong , Wang Hao , Ji Daolin , Jiang Xingming , Li Jinglin , Li Zhenglong , Huang Lining , Zhong Xiangyu , Sun Xueying , Wang Zhidong , Cui Yunfu 
Published: March 2019

AbstractAkirin2 is a key regulator of embryonic development and the innate immunity response. However, this regulator’s role in tumorigenesis especially in cholangiocarcinoma (CCA) development has not been thoroughly elucidated to date. In the current work, we used RT-qPCR, western blot analysis, and immunohistochemistry (IHC) to explore the expression level of Akirin2, and the relationship between Akirin2 levels and clinicopathological characteristics was evaluated. The biological functions of Akirin2 were examined in vitro and in vivo by using a lentiviral vector system. Luciferase reporter assays were applied to detect the direct binding relationship between the 3′-UTR of Akirin2 mRNA and miR-490-3p. The results showed that Akirin2 was overexpressed in CCA and this upregulation was associated with a shorter overall survival. Silencing or overexpressing Akirin2 by lentiviral approaches significantly influenced CCA cell proliferation, migration, invasion, and angiogenesis. An in vivo tumor model further validated the oncogenic effect of Akirin2 on CCA cell growth, metastasis, and angiogenesis. Mechanistic studies demonstrated that Akirin2 induced angiogenesis by increasing the expression of VEGFA by activating the IL-6/STAT3 signaling pathway. Akirin2 promoted cell migratory and invasive potential by affecting the epithelial–mesenchymal transition (EMT) process. In addition, Akirin2 expression was negatively controlled by miR-490-3p in CCA cells, and miR-490-3p attenuated cell migration and angiogenesis in CCA cells by silencing Akirin2. Taken together, the data indicated that Akirin2 could be regulated by miR-490-3p at the posttranscriptional level and facilitate CCA cell progression via the IL-6/STAT3/VEGFA signaling pathway. The present study may expedite the development of novel therapeutic strategies for CCA.
Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression via CCR5
Authors: Nishikawa Gen , Kawada Kenji , Nakagawa Jun , Toda Kosuke , Ogawa Ryotaro , Inamoto Susumu , Mizuno Rei , Itatani Yoshiro , Sakai Yoshiharu 
Published: March 2019

AbstractMesenchymal stem cells (MSCs) are recruited from BM to the stroma of developing tumors, where they serve as critical components of the tumor microenvironment by secreting growth factors, cytokines, and chemokines. The role of MSCs in colorectal cancer (CRC) progression was controversial. In this study, we found that C-C chemokine receptor type 5 (CCR5) ligands (i.e., C-C motif chemokine ligand 3 (CCL3), CCL4, and CCL5) were highly produced from MSCs using a chemokine array screening with conditioned media from the cultured human MSCs. A relatively strong CCR5 expression could be detected within the cytoplasm of several CRC cell lines. Regarding the effect of MSC, we found that the xenografts in which CCR5-overexpressing HCT116 cells were inoculated into immunocompromised mice were highly promoted in vivo by a mixture with MSCs. Notably, the CCR5 inhibitor, maraviroc, significantly abolished the MSC-induced tumor growth in vivo. In human clinical specimens (n = 89), 20 cases (29%) were high for CCR5, whereas 69 cases (71%) were low. Statistical analyses indicated that CCR5 expression in primary CRC was associated with CRC patients’ prognosis. Especially, stage III/IV patients with CCR5-high CRCs exhibited a significantly poorer prognosis than those with CCR5-low CRCs. Furthermore, we investigated the effects of preoperative serum CCR5 ligands on patients’ prognosis (n = 114), and found that CRC patients with high serum levels of CCL3 and CCL4 exhibited a poorer prognosis compared to those with low levels of CCL3 and CCL4, while there was no association between CCL5 and prognosis. These results suggest that the inhibition of MSC–CRC interaction by a CCR5 inhibitor could provide the possibility of a novel therapeutic strategy for CRC, and that serum levels of CCL3 and CCL4 could be predictive biomarkers for the prognosis of CRC patients.
Polymicrobial synergy within oral biofilm promotes invasion of dendritic cells and survival of consortia members
Authors: El-Awady Ahmed , de Sousa Rabelo Mariana , Meghil Mohamed M. , Rajendran Mythilypriya , Elashiry Mahmoud , Stadler Amanda Finger , Foz Adriana Moura , Susin Cristiano , Romito Giuseppe Alexandre , Arce Roger M. , Cutler Christopher W. 
Published: March 2019

AbstractYears of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.
Novel Peptide Inhibitors for Lactate Dehydrogenase A (LDHA): A Survey to Inhibit LDHA Activity via Disruption of Protein-Protein Interaction
Authors: Jafary Farzaneh , Ganjalikhany Mohamad Reza , Moradi Ali , Hemati Mahdie , Jafari Sepideh 
Published: March 2019

AbstractLactate dehydrogenase A (LDHA) is a critical metabolic enzyme belonging to a family of 2-hydroxy acid oxidoreductases that plays a key role in anaerobic metabolism in the cells. In hypoxia condition, the overexpression of LDHA shifts the metabolic pathway of ATP synthesis from oxidative phosphorylation to aerobic glycolysis and the hypoxia condition is a common phenomenon occurred in the microenvironment of tumor cells; therefore, the inhibition of LDHA is considered to be an excellent strategy for cancer therapy. In this study, we employed in silico methods to design inhibitory peptides for lactate dehydrogenase through the disturbance in tetramerization of the enzyme. Using peptide as an anti-cancer agent is a novel approach for cancer therapy possessing some advantages with respect to the chemotherapeutic drugs such as low toxicity, ease of synthesis, and high target specificity. So peptides can act as appropriate enzyme inhibitor in parallel to chemical compounds. In this study, several computational techniques such as molecular dynamics (MD) simulation, docking and MM-PBSA calculation have been employed to investigate the structural characteristics of the monomer, dimer, and tetramer forms of the enzyme. Analysis of MD simulation and protein-protein interaction showed that the N-terminal arms of each subunit have an important role in enzyme tetramerization to establish active form of the enzyme. Hence, N-terminal arm can be used as a template for peptide design. Then, peptides were designed and evaluated to obtain best binders based on the affinity and physicochemical properties. Finally, the inhibitory effect of the peptides on subunit association was measured by dynamic light scattering (DLS) technique. Our results showed that the designed peptides which mimic the N-terminal arm of the enzyme can successfully target the C-terminal domain and interrupt the bona fide form of the enzyme subunits. The result of this study makes a new avenue to disrupt the assembly process and thereby oppress the function of the LDHA.
Deferiprone: Pan-selective Histone Lysine Demethylase Inhibition Activity and Structure Activity Relationship Study
Authors: Khodaverdian Verjine , Tapadar Subhasish , MacDonald Ian A. , Xu Yuan , Ho Po-Yi , Bridges Allison , Rajpurohit Pragya , Sanghani Bhakti A. , Fan Yuhong , Thangaraju Muthusamy , Hathaway Nathaniel A. , Oyelere Adegboyega K. 
Published: March 2019

AbstractDeferiprone (DFP) is a hydroxypyridinone-derived iron chelator currently in clinical use for iron chelation therapy. DFP has also been known to elicit antiproliferative activities, yet the mechanism of this effect has remained elusive. We herein report that DFP chelates the Fe2+ion at the active sites of selected iron-dependent histone lysine demethylases (KDMs), resulting in pan inhibition of a subfamily of KDMs. Specifically, DFP inhibits the demethylase activities of six KDMs - 2A, 2B, 5C, 6A, 7A and 7B - with low micromolar IC50s while considerably less active or inactive against eleven KDMs - 1A, 3A, 3B, 4A-E, 5A, 5B and 6B. The KDM that is most sensitive to DFP, KDM6A, has an IC50that is between 7- and 70-fold lower than the iron binding equivalence concentrations at which DFP inhibits ribonucleotide reductase (RNR) activities and/or reduces the labile intracellular zinc ion pool. In breast cancer cell lines, DFP potently inhibits the demethylation of H3K4me3 and H3K27me3, two chromatin posttranslational marks that are subject to removal by several KDM subfamilies which are inhibited by DFP in cell-free assay. These data strongly suggest that DFP derives its anti-proliferative activity largely from the inhibition of a sub-set of KDMs. The docked poses adopted by DFP at the KDM active sites enabled identification of new DFP-based KDM inhibitors which are more cytotoxic to cancer cell lines. We also found that a cohort of these agents inhibited HP1-mediated gene silencing and one lead compound potently inhibited breast tumor growth in murine xenograft models. Overall, this study identified a new chemical scaffold capable of inhibiting KDM enzymes, globally changing histone modification profiles, and with specific anti-tumor activities.
Prevention of respiratory syncytial virus infection with probiotic lactic acid bacterium Lactobacillus gasseri SBT2055
Authors: Eguchi Kei , Fujitani Naoki , Nakagawa Hisako , Miyazaki Tadaaki 
Published: March 2019

AbstractLactobacillus gasseri SBT2055 (LG2055) is a probiotic lactic acid bacterium with multifunctional effects, including the prevention of influenza A virus infection in mice, reduction of adipocyte size in mice, and increased lifespan in C. elegans. We investigated whether LG2055 exhibits antiviral activity against respiratory syncytial virus (RSV), a global pathogen for which a preventive strategy is required. Following oral administration of LG2055 in mice, the RSV titre in the lung was significantly decreased, while body weight was not decreased after virus infection. Additionally, the elevated expression of pro-inflammatory cytokines in the lung upon RSV infection decreased after LG2055 administration. Moreover, interferon and interferon stimulated genes were upregulated by LG2055 treatment. Comparative cellular proteomic analysis revealed that SWI2/SNF2-related CREB-binding protein activator protein (SRCAP) was a candidate for the antiviral activity of LG2055 against RSV. There was a positive correlation between the inhibition of RSV replication and the suppression of SRCAP expression and RSV replication was suppressed by SRCAP silencing. Since SRCAP is a scaffold protein to which viral non-structural proteins bind, the downregulation of SRCAP induced by LG2055 could provide new insights about the inhibition of RSV replication. In summary, our study demonstrated that LG2055 has prophylactic potential against RSV infection.
Positive selection in Europeans and East-Asians at the ABCA12 gene
Authors: Sirica Roberto , Buonaiuto Marianna , Petrella Valeria , Sticco Lucia , Tramontano Donatella , Antonini Dario , Missero Caterina , Guardiola Ombretta , Andolfi Gennaro , Kumar Heerman , Ayub Qasim , Xue Yali , Tyler-Smith Chris , Salvemini Marco , D’Angelo Giovanni , Colonna Vincenza 
Published: March 2019

AbstractNatural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of theABCA12gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation. We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site ofABCA12. We found no obvious effect of rs10180970 alleles onABCA12gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and present in non-Africans 45,000 years ago.
The association of genetically controlled CpG methylation (cg158269415) of protein tyrosine phosphatase, receptor type N2 (PTPRN2) with childhood obesity
Authors: Lee Suman 
Published: March 2019

AbstractProtein tyrosine phosphatase, receptor type N2 (PTPRN2) encodes a major islet autoantigen in type-1 diabetes. Previous genetic studies have shown its significant association with obesity. PTPRN2 plays an important role in epigenetic regulation of metabolic diseases and cancers. We investigated CpG methylations (cg17429772 and cg158269415) in PTPRN2 by pyrosequencing from blood samples of childhood obesity (n = 638). cg158269415 had significant positive correlations with body mass index (BMI) and waist-hip ratio (WHR). Case-control analysis showed that cg158269415 methylation in blood sample was significantly more hypermethylated in obese cases (n = 252), an average of 2.93% more than that that in controls (n = 386). The cg158269415 methylation has a trimodal distribution pattern with strong dependency on nearby located rs1670344 G > A genotype. Correlations of cg158269415 with BMI and WHR were significant and strong in major G allele carriers (GG + GA). Our study showed that an epigenetic association of PTPRN2 gene with childhood obesity was under certain genetic background. The genetic and epigenetic interplay of PTPRN2 gene may implicate a mechanism of childhood obesity. Whether these small changes in DNA methylation from whole blood are causally or consequently related to childhood obesity outcome and their clinical relevance remains to be determined. However, this study presents a promising obesity risk marker that warrants further investigation.
Re-localization of hormone effectors is associated with dormancy alleviation by temperature and after-ripening in sunflower seeds
Authors: Xia Qiong , Ponnaiah Maharajah , Thanikathansubramanian Kaviya , Corbineau Françoise , Bailly Christophe , Nambara Eiji , Meimoun Patrice , El-Maarouf-Bouteau Hayat 
Published: March 2019

AbstractTemperature is the primary factor that affects seed dormancy and germination. However, the molecular mechanism that underlies its effect on dormancy alleviation remained largely unknown. In this study, we investigate hormone involvement in temperature induced germination as compared to that caused by after-ripening. Dormant (D) sunflower seeds cannot germinate at 10 °C but fully germinate at 20 °C. After-ripened seeds become non-dormant (ND), i.e. able to germinate at 10 °C. Pharmacological experiments showed the importance of abscisic acid (ABA), gibberellins (GAs) and ethylene in temperature- and after-ripening-induced germination of sunflower seeds. Hormone quantification showed that after-ripening is mediated by a decline in both ABA content and sensitivity while ABA content is increased in D seeds treated at 10 or 20 °C, suggesting that ABA decrease is not a prerequisite for temperature induced dormancy alleviation. GAs and ethylene contents were in accordance with germination potential of the three conditions (GA1 was higher in D 20 °C and ND 10 °C than in D 10 °C). Transcripts analysis showed that the major change concerns ABA and GAs metabolism genes, while ABA signalling gene expression was significantly unchanged. Moreover, another level of hormonal regulation at the subcellular localization has been revealed by immunocytolocalization study. Indeed, ABA, protein Abscisic acid-Insensitive 5 (ABI5), involved in ABA-regulated gene expression and DELLA protein RGL2, a repressor of the gibberellins signalling pathway, localized mainly in the nucleus in non-germinating seeds while they localized in the cytosol in germinating seeds. Furthermore, ACC-oxidase (ACO) protein, the key ethylene biosynthesis enzyme, was detected in the meristem only in germinating seeds. Our results reveal the importance of hormone actors trafficking in the cell and their regulation in specialized tissue such as the meristem in dormancy alleviation and germination.
Human electrocortical dynamics while stepping over obstacles
Authors: Nordin Andrew D. , Hairston W. David , Ferris Daniel P. 
Published: March 2019

AbstractTo better understand human brain dynamics during visually guided locomotion, we developed a method of removing motion artifacts from mobile electroencephalography (EEG) and studied human subjects walking and running over obstacles on a treadmill. We constructed a novel dual-layer EEG electrode system to isolate electrocortical signals, and then validated the system using an electrical head phantom and robotic motion platform. We collected data from young healthy subjects walking and running on a treadmill while they encountered unexpected obstacles to step over. Supplementary motor area and premotor cortex had spectral power increases within ~200 ms after object appearance in delta, theta, and alpha frequency bands (3–13 Hz). That activity was followed by similar posterior parietal cortex spectral power increase that decreased in lag time with increasing locomotion speed. The sequence of activation suggests that supplementary motor area and premotor cortex interrupted the gait cycle, while posterior parietal cortex tracked obstacle location for planning foot placement nearly two steps ahead of reaching the obstacle. Together, these results highlight advantages of adopting dual-layer mobile EEG, which should greatly facilitate the study of human brain dynamics in physically active real-world settings and tasks.