bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt/β-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells
Authors: Theka Ilda , Sottile Francesco , Cammisa Marco , Bonnin Sarah , Sanchez-Delgado Marta , Di Vicino Umberto , Neguembor Maria Victoria , Arumugam Karthik , Aulicino Francesco , Monk David , Riccio Andrea , Cosma Maria Pia 
Published: January 2019

AbstractMouse embryonic stem cells (mESCs) are pluripotent and can differentiate into cells belonging to the three germ layers of the embryo. However, mESC pluripotency and genome stability can be compromised in prolonged in vitro culture conditions. Several factors control mESC pluripotency, including Wnt/β-catenin signaling pathway, which is essential for mESC differentiation and proliferation. Here we show that the activity of the Wnt/β-catenin signaling pathway safeguards normal DNA methylation of mESCs. The activity of the pathway is progressively silenced during passages in culture and this results into a loss of the DNA methylation at many imprinting control regions (ICRs), loss of recruitment of chromatin repressors, and activation of retrotransposons, resulting into impaired mESC differentiation. Accordingly, sustained Wnt/β-catenin signaling maintains normal ICR methylation and mESC homeostasis and is a key regulator of genome stability.
Association of prevalent vaginal microbiome of mother with occurrence of type I diabetes in child
Authors: Tejesvi Mysore V. , Nissi Ritva , Saravesi Karita , Pirttilä Anna Maria , Markkola Annamari , Talvensaari-Mattila Anne , Ruotsalainen Anna Liisa 
Published: January 2019

AbstractType I diabetes (T1D) is a rapidly increasing autoimmune disease especially in the Western countries and poses a serious global health problem. Incidence of T1D cannot be fully explained by genetic background, and environmental factors have been assumed to play a role. Environmental conditions and composition of human microbiome have been found to correlate with the incidence of T1D. We asked whether mothers’ prevalent vaginal microbiome could correlate with the incidence of T1D in child. To test this hypothesis, we collected samples of vaginal microbiomes from eight mothers that had at least one child with T1D (child age maximum of 11 years at the time of sampling), born with a vaginal delivery. Eight control mothers had child/children with vaginal delivery and no diabetic child/children. The microbiomes were studied by using 16S rRNA Ion Torrent high throughput sequencing. We found that composition of total and Lactobacillus microbiome was altered, and saw an indication that diversity of vaginal microbiomes of the mothers with a diabetic child could be higher. Based on these pilot observations, we strongly encourage a larger population study to verify whether mother vaginal microbiome diversity and composition are linked to the prevalence of T1D in children.
G9a-dependent histone methylation can be induced in G1 phase of cell cycle
Authors: Fukuda Mikiko , Sakaue-Sawano Asako , Shimura Chikako , Tachibana Makoto , Miyawaki Atsushi , Shinkai Yoichi 
Published: January 2019

AbstractEpigenetic information (epigenome) on chromatin is crucial for the determination of cellular identity and for the expression of cell type-specific biological functions. The cell type-specific epigenome is maintained beyond replication and cell division. Nucleosomes of chromatin just after DNA replication are a mixture of old histones with the parental epigenome and newly synthesized histones without such information. The diluted epigenome is mostly restored within one cell cycle using the epigenome on the parental DNA and nucleosomes as replication templates. However, many important questions about the epigenome replication process remain to be clarified. In this study, we investigated the model system comprising of dimethylated histone H3 lysine 9 (H3K9me2) and its regulation by the lysine methyltransferase G9a. Using this epigenome model system, we addressed whether H3K9me2 can be induced in specific cell cycle stages, especially G1. Using cell cycle-specific degrons, we achieved G1 or late G1-to M phases specific accumulation of exogenous G9a in G9a deficient cells. Importantly, global levels of H3K9me2 were significantly recovered by both cell types. These data indicate that H3K9me2 may be plastic and inducible, even in the long-living, terminally-differentiated, post-mitotic, G0-G1 cell population in vivo. This knowledge is valuable in designing epigenome-manipulation-based treatments for diseases.
Hyperuricemia Predicts an Early Decline in Renal Function among Older People: A Community-Based Cohort Study
Authors: Tseng Wei-Cheng , Chen Yung-Tai , Lin Yao-Ping , Ou Shuo-Ming , Yang Chih-Yu , Lin Chi-Hung , Tarng Der-Cherng ,   The Taiwan Geriatric Kidney Disease (TGKD) Research Group, Tarng Der-Cherng , Tseng Wei-Cheng , Tsai Ming-Tsun , Ou Shuo-Ming , Yang Chih-Yu , Lin Yao-Ping , Chen Yu-Hsin , Chuang Yi-Fang , Chen Liang-Kung , Wang Kwua-Yun , Shih Chia-Jen , Chen Yung-Tai , Lin Yi-Sheng , Hung Szu-Chun , Kuo Ko-Lin , Hung Tung-Po , Hu Fen-Hsiang , Chen Nien-Jung , Chen Yu-Chi , Lin Chi-Hung , Tsai Tung-Hu , Hsieh Shie-Liang , Wei Yau-Huei , Hsu Chih-Cheng , Liu Jia-Sin , Chang Yu-Kang , Chiang Ming-Han 
Published: January 2019

AbstractWhether elevated serum uric acid levels (SUA) predict renal dysfunction remains controversial in the elderly. Therefore, we investigated the association between SUA and early renal function decline defined as an estimated glomerular filtration rate (eGFR) reduction ≥30% over 2 years. From 2001 to 2010, we conducted a longitudinal cohort study comprising 44,078 participants aged ≥65 years in the Taipei City Elderly Health Examination Database. Participants were classified by 1-mg/dL increment of SUA. We used multivariable logistic and Cox regression analyses to compare the risk of early renal function decline in different SUA groups. Compared to the reference SUA group of 5.0–5.9 mg/dL, hyperuricemic participants had increased risks of eGFR decline, starting at SUA ≥6.0 mg/dL (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] = 1.00–1.45). The risk progressively elevated as SUA increased, with the highest in the SUA ≥10.0 mg/dL group (aOR = 3.20, CI = 2.39–4.28). Multivariable Cox regression further confirmed that hyperuricemia was 1.12-fold (CI = 1.03–1.22, SUA ≥6.0 mg/dL) to 1.6-fold (CI = 1.37–1.86, SUA ≥10.0 mg/dL) more likely to develop early eGFR decline. Hyperuricemia-associated increased risks for early eGFR decline were consistent across subgroup and sensitivity analyses. Collectively, SUA ≥6.0 mg/dL independently predicted early renal dysfunction with eGFR decline ≥30% over 2 years in older people.
Systematic characterization of position one variants within the lantibiotic nisin
Authors: Lagedroste Marcel , Reiners Jens , Smits Sander H. J. , Schmitt Lutz 
Published: January 2019

AbstractLantibiotics are a growing class of natural compounds, which possess antimicrobial activity against a broad range of Gram-positive bacteria. Their high potency against human pathogenic strains such as MRSA and VRE makes them excellent candidates as substitutes for classic antibiotics in times of increasing multidrug resistance of bacterial strains. New lantibiotics are detected in genomes and can be heterologously expressed. The functionality of these novel lantibiotics requires a systematic purification and characterization to benchmark them against for example the well-known lantibiotic nisin. Here, we used a standardized workflow to characterize lantibiotics consisting of six individual steps. The expression and secretion of the lantibiotic was performed employing the promiscuous nisin modification machinery. We mutated the first amino acid of nisin into all proteinaceous amino acids and compared their bactericidal potency against sensitive strains as well as strains expressing nisin resistance proteins. Interestingly, we can highlight four distinct groups based on the residual activity of nisin against sensitive as well as resistant L. lactis strains.
Contributions of modern Gobi Desert to the Badain Jaran Desert and the Chinese Loess Plateau
Authors: Wang Xunming , Cai Diwen , Sun Jimin , Lu Huayu , Liu Wenbin , Qiang Mingrui , Cheng Hong , Che Huizheng , Hua Ting , Zhang Caixia 
Published: January 2019

AbstractIt is well known that the Gobi Desert is the dominant source area of the Badain Jaran Desert (BJD) and the Chinese Loess Plateau (CLP). However, due to the absence of quantitative analyses, there are nearly no exact assessments of its actual contribution. Combinations of field investigations, wind tunnel experiments, and wind field analyses revealed that the potential erosion depth on modern Gobi Desert varied between 0.41 and 0.89 mm a−1. Results indicated it would take an average theoretical time of 80.8 ka and 4,475.9 ka to form the current dimensions of the BJD and CLP, respectively, which means the Gobi Desert may provide substantial sand sources to the modern BJD, while its contribution to the loess of modern CLP might be overestimated despite it was the key sources of the CLP in Quaternary.
Musculoskeletal study of cebocephalic and cyclopic lamb heads illuminates links between normal and abnormal development, evolution and human pathologies
Authors: Diogo Rui , Razmadze Daria , Siomava Natalia , Douglas Nora , Fuentes Jose S. M. , Duerinckx Andre 
Published: January 2019

AbstractThis paper is part of the emerging field of Evolutionary Developmental Pathology, dedicated to study the links between normal and abnormal development, evolution and human pathologies. We analyzed the head musculoskeletal system of several ‘natural mutant’ newborn lambs displaying various degrees of abnormality, from mild defects to cebocephaly and to cyclopia, and compared them with humans. Interestingly, muscle defects are less marked than osteological ones, and contrarily to the latter they tend to display left-right assymetries. In individuals with cebocephalic and even cyclopic skulls almost all head muscles are normal. The very few exceptions are some extraocular muscles and facial muscles that normally attach to osteological structures that are missing in the abnormal heads: such muscles are instead attached to the ‘nearest topological neighbor’ of the missing osteological structure, a pattern also found in cyclopic humans. These observations support Alberch’s ill-named “logic of monsters” - as a byproduct of strong developmental/topological constraints anatomical patterns tend to repeat themselves, even severe malformations displayed by distantly related taxa. They also support the idea that mammalian facial muscles reverted to an ancestral ‘nearest-neighbor’ muscle-bone type of attachment seen in non-vertebrate animals and in vertebrate limbs, but not in other vertebrate head muscles.
Ecosystem metabolism drives pH variability and modulates long-term ocean acidification in the Northeast Pacific coastal ocean
Authors: Lowe Alexander T. , Bos Julia , Ruesink Jennifer 
Published: January 2019

AbstractOcean acidification poses serious threats to coastal ecosystem services, yet few empirical studies have investigated how local ecological processes may modulate global changes of pH from rising atmospheric CO2. We quantified patterns of pH variability as a function of atmospheric CO2 and local physical and biological processes at 83 sites over 25 years in the Salish Sea and two NE Pacific estuaries. Mean seawater pH decreased significantly at −0.009 ± 0.0005 pH yr−1 (0.22 pH over 25 years), with spatially variable rates ranging up to 10 times greater than atmospheric CO2-driven ocean acidification. Dissolved oxygen saturation (%DO) decreased by −0.24 ± 0.036% yr−1, with site-specific trends similar to pH. Mean pH shifted from <7.6 in winter to >8.0 in summer concomitant to the seasonal shift from heterotrophy (%DO < 100) to autotrophy (%DO > 100) and dramatic shifts in aragonite saturation state critical to shell-forming organisms (probability of undersaturation was >80% in winter, but <20% in summer). %DO overwhelmed the influence of atmospheric CO2, temperature and salinity on pH across scales. Collectively, these observations provide evidence that local ecosystem processes modulate ocean acidification, and support the adoption of an ecosystem perspective to ocean acidification and multiple stressors in productive aquatic habitats.
A homozygous missense variant in the alkaline phosphatase gene ALPL is associated with a severe form of canine hypophosphatasia
Authors: Kyöstilä Kaisa , Syrjä Pernilla , Lappalainen Anu K. , Arumilli Meharji , Hundi Sruthi , Karkamo Veera , Viitmaa Ranno , Hytönen Marjo K. , Lohi Hannes 
Published: January 2019

AbstractInherited skeletal disorders affect both humans and animals. In the current study, we have performed series of clinical, pathological and genetic examinations to characterize a previously unreported skeletal disease in the Karelian Bear Dog (KBD) breed. The disease was recognized in seven KBD puppies with a variable presentation of skeletal hypomineralization, growth retardation, seizures and movement difficulties. Exome sequencing of one affected dog revealed a homozygous missense variant (c.1301T > G; p.V434G) in the tissue non-specific alkaline phosphatase gene, ALPL. The identified recessive variant showed full segregation with the disease in a cohort of 509 KBDs with a carrier frequency of 0.17 and was absent from 303 dogs from control breeds. In humans, recessive and dominant ALPL mutations cause hypophosphatasia (HPP), a metabolic bone disease with highly heterogeneous clinical manifestations, ranging from lethal perinatal hypomineralization to a relatively mild dental disease. Our study reports the first naturally occurring HPP in animals, resembling the human infantile form. The canine HPP model may serve as a preclinical model while a genetic test will assist in breeding programs.
Differentiating between cancer and normal tissue samples using multi-hit combinations of genetic mutations
Authors: Dash Sajal , Kinney Nicholas A. , Varghese Robin T. , Garner Harold R. , Feng Wu-chun , Anandakrishnan Ramu 
Published: January 2019

AbstractCancer is known to result from a combination of a small number of genetic defects. However, the specific combinations of mutations responsible for the vast majority of cancers have not been identified. Current computational approaches focus on identifying driver genes and mutations. Although individually these mutations can increase the risk of cancer they do not result in cancer without additional mutations. We present a fundamentally different approach for identifying the cause of individual instances of cancer: we search for combinations of genes with carcinogenic mutations (multi-hit combinations) instead of individual driver genes or mutations. We developed an algorithm that identified a set of multi-hit combinations that differentiate between tumor and normal tissue samples with 91% sensitivity (95% Confidence Interval (CI) = 89–92%) and 93% specificity (95% CI = 91–94%) on average for seventeen cancer types. We then present an approach based on mutational profile that can be used to distinguish between driver and passenger mutations within these genes. These combinations, with experimental validation, can aid in better diagnosis, provide insights into the etiology of cancer, and provide a rational basis for designing targeted combination therapies.
Identification of 12 genetic loci associated with human healthspan
Authors: Zenin Aleksandr , Tsepilov Yakov , Sharapov Sodbo , Getmantsev Evgeny , Menshikov L. I. , Fedichev Peter O. , Aulchenko Yurii 
Published: January 2019

AbstractAging populations face diminishing quality of life due to increased disease and morbidity. These challenges call for longevity research to focus on understanding the pathways controlling healthspan. We use the data from the UK Biobank (UKB) cohort and observe that the risks of major chronic diseases increased exponentially and double every eight years, i.e., at a rate compatible with the Gompertz mortality law. Assuming that aging drives the acceleration in morbidity rates, we build a risk model to predict the age at the end of healthspan depending on age, gender, and genetic background. Using the sub-population of 300,447 British individuals as a discovery cohort, we identify 12 loci associated with healthspan at the whole-genome significance level. We find strong genetic correlations between healthspan and all-cause mortality, life-history, and lifestyle traits. We thereby conclude that the healthspan offers a promising new way to interrogate the genetics of human longevity.
A cyclic peptide reproducing the α1 helix of VEGF-B binds to VEGFR-1 and VEGFR-2 and inhibits angiogenesis and tumor growth
Authors: Assareh Elham , Mehrnejad Faramarz , Mansouri Kamran , Esmaeili Rastaghi Ahmad Reza , Naderi-Manesh Hossein , Asghari S. Mohsen 
Published: January 2019

Abstract
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are pivotal regulators of angiogenesis. The VEGF–VEGFR system is therefore an important target of anti-angiogenesis therapy. Based on the X-ray structure of VEGF-B/VEGFR-1 D2, we designed a cyclic peptide (known as VGB1) reproducing the α1 helix and its adjacent region to interfere with signaling through VEGFR-1. Unexpectedly, VGB1 bound VEGFR-2 in addition to VEGFR-1, leading to inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells and 4T1 murine mammary carcinoma cells, which express VGEFR-1 and VEGFR-2, and U87 glioblastoma cells that mostly express VEGFR-2. VGB1 inhibited different aspects of angiogenesis, including proliferation, migration and tube formation of endothelial cells stimulated by VEGF-A through suppression of extracellular signal-regulated kinase 1/2 and AKT (Protein Kinase B) phosphorylation. In a murine 4T1 mammary carcinoma model, VGB1 caused regression of tumors without causing weight loss in association with impaired cell proliferation (decreased Ki67 expression) and angiogenesis (decreased CD31 and CD34 expression), and apoptosis induction (increased TUNEL staining and p53 expression, and decreased Bcl-2 expression). According to far-UV circular dichroism (CD) and molecular dynamic simulation data, VGB1 can adopt a helical structure. These results, for the first time, demonstrate that α1 helix region of VEGF-B recognizes both VEGFR-1 and VEGFR-2.
Evaluating the suitability of groundwater for drinking purposes in the North Chengdu Plain, China
Authors: Mohamed Adam Khalifa , Dan Liu , Kai Song , Eldaw Elsiddig , Abualela Salma 
Published: January 2019

Groundwater is a significant and crucial component for all development activities of any life support system. In this study, the hydrochemical analysis and water quality index method (WQI) were used to assess groundwater quality for drinking purposes. Twelve groundwater samples were collected and analyzed into fourteen parameters which were considered as important indicators for assessing groundwater quality. A comparative study of these parameters with that of the Chinese Groundwater Standard (GB/T14848-2017) was conducted. It can be depicted from the results that groundwater quality is categorized as very hard, fresh water and slightly alkaline in nature. The major sequence of dominant cations and anions in groundwater are Ca2+ >	Mg2+ > Na+ > K+ and HCO-3 > SO2-4 > Cl- respectively. From the total 12 samples analyzed, the parameters of TH, NH+4, Fe and Mn of samples exceeded the limits set by (GB/T14848-2017) standard. Piper diagram illustrated that groundwater samples of the studied area are mostly of Ca-Mg-HCO3-SO4 type. WQI showed all samples fall between excellent to good category of water and suitable for drinking purposes. The quality of groundwater is mainly affected from anthropogenic activities and natural influence. The proposed method is reliable and effcient for groundwater pollution assessment and can be used in decision-making.
Behavioral disorders in adolescents and Orthodontics Attitude of orthodontists? How far to go?
Authors: Thery-Hugly M.-C. 
Published: January 2019

Adults are often worried and somewhat shocked by teenagers’ behavior, and their way of learning, the so-called “Adolescence Disorders.”
The lack of assertiveness of adolescents is the most important issue in the management of orthodontic treatment. With the desirable attitude of empathy in mind, for the majority of teenagers, the orthodontist will manage treatment in a quiet and optimal way.
For 15% of them however, real problems such as anxiety, depression or personality disorders may appear. The use of CBT will be useful.
The orthodontist must be empathetic enough to guide these young teenagers in their development, through their “mouth,” this organ is psychologically invested to fundamental symbols of life and learning.
Induction of Secondary Metabolites from the Marine-Derived Fungus Aspergillus versicolor through Co-cultivation with Bacillus subtilis
Authors: Abdel-Wahab Nada , Scharf Sebastian , Özkaya Ferhat , Kurtán Tibor , Mándi Attila , Fouad Mostafa , Kamel Mohamed , Müller Werner , Kalscheuer Rainer , Lin Wenhan , Daletos Georgios , Ebrahim Weaam , Liu Zhen , Proksch Peter 
Published: January 2019

AbstractA new cyclic pentapeptide, cotteslosin C (1), a new aflaquinolone, 22-epi-aflaquinolone B (3), and two new anthraquinones (9 and 10), along with thirty known compounds (2, 4 – 8, 11 – 34) were isolated from a co-culture of the sponge-associated fungus Aspergillus versicolor with Bacillus subtilis. The new metabolites were only detected in the co-culture extract, but not when the fungus was grown under axenic conditions. Furthermore, the co-culture extract exhibited an enhanced accumulation of the known constituents versicolorin B (14), averufin (16), and sterigmatocyctin (19) by factors of 1.5, 2.0, and 4.7, respectively, compared to the axenic fungal culture. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR spectra and mass spectrometry as well as by comparison with literature data. The absolute configuration of compounds 3, 9, and 10 was determined by ECD (electronic circular dichroism) analysis aided by TDDFT-ECD (time-dependent density functional theory electronic circular dichroism) calculations. Compounds 15, 18 – 21, and 26 exhibited strong to moderate cytotoxic activity against the mouse lymphoma cell line L5178Y, with IC50 values ranging from 2.0 to 21.2 µM, while compounds 14, 16, 31, 32, and 33 displayed moderate inhibitory activities against several gram-positive bacteria, with MIC values ranging from 12.5 to 50 µM.