bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic risk factors identified in populations of European descent do not improve the prediction of osteoporotic fracture and bone mineral density in Chinese populations
Authors: Li Yu-Mei , Peng Cheng , Zhang Ji-Gang , Zhu Wei , Xu Chao , Lin Yong , Fu Xiao-Ying , Tian Qing , Zhang Lei , Xiang Yang , Sheng Victor , Deng Hong-Wen 
Published: April 2019

AbstractAiming to investigate whether genetic risk factors (GRFs) for fracture and bone mineral density (BMD) identified from people of European descent can help improve the prediction of osteoporotic fracture (OF) risk and BMD in Chinese populations, we built assessment models for femoral neck (FN)-fracture prediction and BMD value prediction using 700 elderly Chinese Han subjects and 1,620 unrelated Chinese Han subjects, respectively. 17 fracture-associated genes and 82 FN-BMD associated genes identified in people of European descent were used to build a logistic regression model with clinical risk factors (CRFs) for FN-fracture prediction in Chinese. Meanwhile 107 BMD-associated genes from people of European descent were used to build a multiple linear regression model with CRFs for BMD prediction in Chinese. A Lasso algorithm was employed for informative SNP selection to construct the genetic risk score (GRS) with ten-fold cross-validation. The results showed that, adding fracture GRF and FN-BMD GRF to the model with CRFs, the area under the receiver operating characteristic curve (AUC) decrease from 0.653 to 0.587 and 0.588, respectively, for FN fracture prediction. 62.3% and 61.8% of the risk variation were explained by the Model with CRFs and fracture GRF and by the Model with CRFs and FN-BMD GRF, respectively, as compared to 65.5% in the Model with CRFs only. The net reclassification improvement (NRI) index in the reclassification analysis is 0.56% (P = 0.57) and 1.13% (P = 0.29), respectively. There is no significant difference either between the performance of the model with CRFs and that of the model with both CRFs and GRF for BMD prediction. We concluded that, in the current study, GRF of fracture identified in people of European descent does not contributes to improve the fracture prediction in Chinese; and GRF of BMD from people of European descent cannot help improve the accuracy of the fracture prediction in Chinese perhaps partially because GRF of BMD from people of European descent may not contribute to BMD prediction in Chinese. This study highlights the limited utility of the current genetics studies largely focused on people of European descent for disease or risk factor prediction in other ethnic groups, and calls for more and larger scale studies focused on other ethnic groups.
Theta oscillations in 4-year-olds are sensitive to task engagement and task demands
Authors: Meyer Marlene , Endedijk Hinke M. , van Ede Freek , Hunnius Sabine 
Published: April 2019

AbstractTop-down control processes are essential for guiding attention and working memory towards task-relevant information. Recently, theta oscillations were suggested as critical for these cognitive processes. Infant studies testing a mixture of bottom-up and top-down processes support adult theta findings. Yet, since infants cannot be instructed, it remains unclear to what extent theta oscillations are involved particularly in top-down control in early childhood. That is especially relevant towards school age when children need top-down control to solve the increasingly complex tasks. In this EEG study, we investigated whether theta-power in 4-year-olds is sensitive to task engagement and to different cognitive task demands. In a within-subjects design, children had three different instructions before watching videos including either no demands (No Task), language-related (Color-naming Task), or action-related (Imitation Task) demands. We analyzed children’s theta-power (3–6 Hz) in two contrasts: (1) Task vs. No Task and (2) Color-naming vs. Imitation Task. The findings revealed more frontomedial theta-power when children were engaged in a task and their frontomedial theta-power increased during their cognitive engagement. Theta-power was stronger over left fronto-temporal sites for language- compared to action-related demands. These findings support recent theoretical work highlighting theta oscillations in top-down control and extend this neurocognitive framework to preschoolers.
Linear Mitochondrial Genome in Anthozoa (Cnidaria): A Case Study in Ceriantharia
Authors: Stampar Sérgio N. , Broe Michael B. , Macrander Jason , Reitzel Adam M. , Brugler Mercer R. , Daly Marymegan 
Published: April 2019

AbstractSequences and structural attributes of mitochondrial genomes have played a critical role in the clarification of relationships among Cnidaria, a key phylum of early-diverging animals. Among the major lineages of Cnidaria, Ceriantharia (“tube anemones”) remains one of the most enigmatic in terms of its phylogenetic position. We sequenced the mitochondrial genomes of two ceriantharians to see whether the complete organellar genome would provide more support for the phylogenetic placement of Ceriantharia. For both Isarachnanthus nocturnus and Pachycerianthus magnus, the mitochondrial gene sequences could not be assembled into a single circular genome. Instead, our analyses suggest that both species have mitochondrial genomes consisting of multiple linear fragments. Linear mitogenomes are characteristic of members of Medusozoa, one of the major lineages of Cnidaria, but are unreported for Anthozoa, which includes the Ceriantharia. The inferred number of fragments and variation in gene order between species is much greater within Ceriantharia than among the lineages of Medusozoa. We identify origins of replication for each of the five putative chromosomes of the Isarachnanthus nocturnus mitogenome and for each of the eight putative chromosomes of the Pachycerianthus magnus mitogenome. At 80,923 bp, I. nocturnus now holds the record for the largest animal mitochondrial genome reported to date. The novelty of the mitogenomic structure in Ceriantharia highlights the distinctiveness of this lineage but, because it appears to be both unique to and diverse within Ceriantharia, it is uninformative about the phylogenetic position of Ceriantharia relative to other Anthozoa. The presence of tRNAMet and tRNATrp in both ceriantharian mitogenomes supports a closer relationship between Ceriantharia and Hexacorallia than between Ceriantharia and any other cnidarian lineage, but phylogenetic analysis of the genes contained in the mitogenomes suggests that Ceriantharia is sister to a clade containing Octocorallia + Hexacorallia indicating a possible suppression of tRNATrp in Octocorallia.
Decreased Total Iron Binding Capacity May Correlate with Ruptured Intracranial Aneurysms
Authors: Can Anil , Lai Pui Man Rosalind , Castro Victor M. , Yu Sheng , Dligach Dmitriy , Finan Sean , Gainer Vivian , Shadick Nancy A. , Savova Guergana , Murphy Shawn , Cai Tianxi , Weiss Scott T. , Du Rose 
Published: April 2019

AbstractIron and its derivatives play a significant role in various physiological and biochemical pathways, and are influenced by a wide variety of inflammatory, infectious, and immunological disorders. We hypothesized that iron and its related factors play a role in intracranial aneurysm pathophysiology and investigated if serum iron values are associated with ruptured intracranial aneurysms. 4,701 patients with 6,411 intracranial aneurysms, including 1201 prospective patients, who were diagnosed at the Massachusetts General Hospital and Brigham and Women’s Hospital between 1990 and 2016 were evaluated. A total of 366 patients with available serum iron, ferritin and total iron binding capacity (TIBC) values were ultimately included in the analysis. 89% of included patients had anemia. Patients were categorized into ruptured and non-ruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the association between ruptured aneurysms and iron, ferritin, and TIBC. TIBC values (10−3 g/L) within 1 year of diagnosis (OR 0.41, 95% CI 0.28–0.59) and between 1 and 3 years from diagnosis (OR 0.52, 95% CI 0.29–0.93) were significantly and inversely associated with intracranial aneurysm rupture. In contrast, serum iron and ferritin were not significant. In this case-control study, low TIBC was significantly associated with ruptured aneurysms, both in the short- and long term. However, this association may not apply to the general population as there may be a selection bias as iron studies were done in a subset of patients only.
A rare autism-associated MINT2/APBA2 mutation disrupts neurexin trafficking and synaptic function
Authors: Lin Amy Y. , Henry Shawna , Reissner Carsten , Neupert Christian , Kenny Connor , Missler Markus , Beffert Uwe , Ho Angela 
Published: April 2019

AbstractMINT2/APBA2 is a synaptic adaptor protein involved in excitatory synaptic transmission. Several nonsynonymous coding variants in MINT2 have been identified in autism spectrum disorders (ASDs); however, these rare variants have not been examined functionally and the pathogenic mechanisms are unknown. Here, we examined the synaptic effects of rat Mint2 N723S mutation (equivalent to autism-linked human MINT2 N722S mutation) which targets a conserved asparagine residue in the second PDZ domain of Mint2 that binds to neurexin-1α (Nrxn1α), a presynaptic cell-adhesion protein implicated in ASDs. We show the N723S mutation impairs Nrxn1α stabilization and trafficking to the membrane while binding to Nrxn1α remains unaffected. Using time-lapse imaging in primary mouse neurons, we found that the N723S mutant had more immobile puncta at neuronal processes compared to Mint2 wild type. We therefore, reasoned that the N723S mutant may alter the co-transport of Nrxn1α at axonal processes to presynaptic terminals. Indeed, we found the N723S mutation affected Nrxn1α localization at presynaptic terminals which correlated with a decrease in Nrxn-mediated synaptogenesis and miniature event frequency in excitatory synapses. Together, our data reveal Mint2 N723S leads to neuronal dysfunction, in part due to alterations in Nrxn1α surface trafficking and synaptic function of Mint2.
Release of eDNA by different life history stages and during spawning activities of laboratory-reared Japanese eels for interpretation of oceanic survey data
Authors: Takeuchi Aya , Iijima Takuya , Kakuzen Wataru , Watanabe Shun , Yamada Yoshiaki , Okamura Akihiro , Horie Noriyuki , Mikawa Naomi , Miller Michael J. , Kojima Takahito , Tsukamoto Katsumi 
Published: April 2019

AbstractTo assist in detection of offshore spawning activities of the Japanese eel Anguilla japonica and facilitate interpretation of results of environmental DNA (eDNA) analysis in their spawning area, we examined the eDNA concentration released by each life history stage of artificially reared Japanese eels in the laboratory using quantitative real-time PCR (qPCR). We also compared eDNA concentrations between before and after artificially induced spawning activities. eDNA was not detected from three 30 L seawater tanks containing each single fertilized egg, but eDNA was found from other tanks each containing single individuals of larval stages (preleptocephalus and leptocephalus), juvenile stages (glass eel, elver and yellow eel) or adult stage (silver eel). The eDNA concentrations increased in the life history stages, showed a significant difference among all stages, and were positively correlated with the total length and wet weight. Moreover, the eDNA concentration after spawning was 10–200 times higher than that before spawning, which indicated that the spawning events in the ocean would produce relatively high eDNA concentration. These results in the laboratory suggested that eDNA analysis appears to be an effective method for assisting oceanic surveys to estimate the presence and spawning events of the Japanese eel in the spawning area.
Kynurenic acid as the neglected ingredient of commercial baby formulas
Authors: Milart Pawel , Paluszkiewicz Piotr , Dobrowolski Piotr , Tomaszewska Ewa , Smolinska Katarzyna , Debinska Iwona , Gawel Kinga , Walczak Katarzyna , Bednarski Jerzy , Turska Monika , Raban Michal , Kocki Tomasz , Turski Waldemar A. 
Published: April 2019

AbstractThe global increase in resorting to artificial nutritional formulas replacing breastfeeding has been identified among the complex causes of the obesity epidemic in infants and children. One of the factors recently recognized to influence metabolism and weight gain is kynurenic acid (KYNA), an agonist of G protein-coupled receptor (GPR35). Therefore the aim of the study was to determine the concentration of KYNA in artificial nutritional formulas in comparison with its level in human breast milk and to evaluate developmental changes in rats exposed to KYNA enriched diet during the time of breastfeeding. KYNA levels were measured in milk samples from 25 heathy breast-feeding women during the first six months after labor and were compared with 21 time-adjusted nutritional formulas. Animal experiments were performed on male Wistar rats. KYNA was administered in drinking water. The content of KYNA in human milk increases more than 13 times during the time of breastfeeding while its level is significantly lower in artificial formulas. KYNA was detected in breast milk of rats and it was found that the supplementation of rat maternal diet with KYNA in drinking water results in its increase in maternal milk. By means of the immunoblotting technique, GPR35 was evidenced in the mucosa of the jejunum of 1-day-old rats and distinct morphological changes in the jejunum of 21-day-old rats fed by mothers exposed to water supplemented with KYNA were found. A significant reduction of body weight gain of rats postnatally exposed to KYNA supplementation without changes in total body surface and bone mineral density was observed. The rat offspring fed with breast milk with artificially enhanced KYNA content demonstrated a lower mass gain during the first 21 days of life, which indicates that KYNA may act as an anti-obesogen. Further studies are, therefore, warranted to investigate the mechanisms regulating KYNA secretion via breast milk, as well as the influence of breast milk KYNA on mass gain. In the context of lifelong obesity observed worldwide in children fed artificially, our results imply that insufficient amount of KYNA in baby formulas could be considered as one of the factors associated with increased mass gain.
Automated 3D Axonal Morphometry of White Matter
Authors: Abdollahzadeh Ali , Belevich Ilya , Jokitalo Eija , Tohka Jussi , Sierra Alejandra 
Published: April 2019

AbstractAxonal structure underlies white matter functionality and plays a major role in brain connectivity. The current literature on the axonal structure is based on the analysis of two-dimensional (2D) cross-sections, which, as we demonstrate, is precarious. To be able to quantify three-dimensional (3D) axonal morphology, we developed a novel pipeline, called ACSON (AutomatiC 3D Segmentation and morphometry Of axoNs), for automated 3D segmentation and morphometric analysis of the white matter ultrastructure. The automated pipeline eliminates the need for time-consuming manual segmentation of 3D datasets. ACSON segments myelin, myelinated and unmyelinated axons, mitochondria, cells and vacuoles, and analyzes the morphology of myelinated axons. We applied the pipeline to serial block-face scanning electron microscopy images of the corpus callosum of sham-operated (n = 2) and brain injured (n = 3) rats 5 months after the injury. The 3D morphometry showed that cross-sections of myelinated axons were elliptic rather than circular, and their diameter varied substantially along their longitudinal axis. It also showed a significant reduction in the myelinated axon diameter of the ipsilateral corpus callosum of rats 5 months after brain injury, indicating ongoing axonal alterations even at this chronic time-point.
Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia
Authors: Rashidi Armin , Kaiser Thomas , Shields-Cutler Robin , Graiziger Carolyn , Holtan Shernan G. , Rehman Tauseef Ur , Wasko Justin , Weisdorf Daniel J. , Dunny Gary , Khoruts Alexander , Staley Christopher 
Published: April 2019

AbstractAcute leukemia (AL) patients undergoing intensive induction chemotherapy develop severe gut dysbiosis, placing them at heightened risk for infectious complications. Some AL patients will undergo “repeat therapy” (re-induction or salvage) due to persistent or relapsed disease. We hypothesized that prior injury to the microbiome during induction may influence dysbiosis patterns during repeat therapy. To test this hypothesis, we analyzed the bacterial microbiome profiles of thrice-weekly stool samples from 20 intensively treated AL patients (first induction: 13, repeat therapy: 7) by 16S rRNA sequencing. In mixed-effects modeling, repeat therapy was a significant predictor of Enterococcus expansion (P = 0.006), independently of antibiotic exposure, disease type, feeding mode, and week of chemotherapy. Bayesian analysis of longitudinal data demonstrated larger departures of microbial communities from the pre-chemotherapy baseline during repeat therapy compared to induction. This increased ecosystem instability during repeat therapy possibly impairs colonization resistance and increases vulnerability to Enterococcus outgrowth. Microbiota restoration therapies at the end of induction or before starting subsequent therapy warrant investigation.
Leveraging deep learning to understand health beliefs about the Human Papillomavirus Vaccine from social media
Authors: Du Jingcheng , Cunningham Rachel M. , Xiang Yang , Li Fang , Jia Yuxi , Boom Julie A. , Myneni Sahiti , Bian Jiang , Luo Chongliang , Chen Yong , Tao Cui 
Published: April 2019

AbstractOur aim was to characterize health beliefs about the human papillomavirus (HPV) vaccine in a large set of Twitter posts (tweets). We collected a Twitter data set related to the HPV vaccine from 1 January 2014, to 31 December 2017. We proposed a deep-learning-based framework to mine health beliefs on the HPV vaccine from Twitter. Deep learning achieved high performance in terms of sensitivity, specificity, and accuracy. A retrospective analysis of health beliefs found that HPV vaccine beliefs may be evolving on Twitter.
Arsinothricin, an arsenic-containing non-proteinogenic amino acid analog of glutamate, is a broad-spectrum antibiotic
Authors: Nadar Venkadesh Sarkarai , Chen Jian , Dheeman Dharmendra S. , Galván Adriana Emilce , Yoshinaga-Sakurai Kunie , Kandavelu Palani , Sankaran Banumathi , Kuramata Masato , Ishikawa Satoru , Rosen Barry P. , Yoshinaga Masafumi 
Published: April 2019

AbstractThe emergence and spread of antimicrobial resistance highlights the urgent need for new antibiotics. Organoarsenicals have been used as antimicrobials since Paul Ehrlich’s salvarsan. Recently a soil bacterium was shown to produce the organoarsenical arsinothricin. We demonstrate that arsinothricin, a non-proteinogenic analog of glutamate that inhibits glutamine synthetase, is an effective broad-spectrum antibiotic against both Gram-positive and Gram-negative bacteria, suggesting that bacteria have evolved the ability to utilize the pervasive environmental toxic metalloid arsenic to produce a potent antimicrobial. With every new antibiotic, resistance inevitably arises. The arsN1 gene, widely distributed in bacterial arsenic resistance (ars) operons, selectively confers resistance to arsinothricin by acetylation of the α-amino group. Crystal structures of ArsN1 N-acetyltransferase, with or without arsinothricin, shed light on the mechanism of its substrate selectivity. These findings have the potential for development of a new class of organoarsenical antimicrobials and ArsN1 inhibitors.
Functional study of the association of CHI3L1 polymorphisms with asthma susceptibility in the Southwest Chinese Han population
Authors: Chen Guo , Zhang Miao-Miao , Wang Yu , Wu Shou-Quan , Wang Ming-Gui , He Jian-Qing 
Published: April 2019

Abstract
Background: Chitinase 3-like 1 (CHI3L1) is involved in the Th2 cell mediated pathway, tissue remodeling and fibrosis. Correlations of CHI3L1 gene polymorphisms with asthma in previous studies have been inconsistent. The present study was designed to investigate the association between CHI3L1 polymorphisms and asthma in the southwest Chinese Han population. Methods: Two single nucleotide polymorphisms (SNPs), rs4950928 and rs10399931, were genotyped in 410 asthma patients and 418 healthy controls from Southwest China. Dual-luciferase reporter gene analysis was performed to detect allele-dependent promoter activity of CHI3L1 variants in HEK293 cells. Real-time quantitative PCR was applied to detect the relative mRNA expression associated with different genotypes of CHI3L1 rs10399931. A meta-analysis was performed using data collected from previously published reports and the present study. Results: No significant association was found between rs4950928 and asthma. The rs10399931 CT/TT genotype increased the risk of asthma under the dominant model (P = 0.031, OR = 1.428, 95% CI, 1.033–1.974), while the CT genotype showed the same tendency under the heterozygous model (P = 0.003, OR = 1.680, 95% CI, 1.186–2.380). No statistically significant difference was found between alleles T and C of rs10399931in the dual-luciferase reporter gene analysis (P = 0.201). The rs10399931 CT/TT genotypes reduced the relative mRNA expression detected by real-time quantitative PCR (P = 0.002). There was no significant association between the CHI3L1 rs4950928 polymorphism and the risk of asthma in the meta-analysis. Conclusion: In the southwest Chinese Han population, the CHI3L1 rs10399931 CT/TT genotypes may increase the risk of asthma. rs10399931 may be a functional variant of CHI3L1 due to its effect on mRNA expression.
Notch signaling pathway regulates CD4+CD25+CD127dim/− regulatory T cells and T helper 17 cells function in gastric cancer patients
Authors: Yang Lu , Zhao Ke-Lei , Qin Lei , Ji Dan-Xia , Zhang Bin , Zheng Peng-Fei , Qin Yong-Mei 
Published: April 2019

Abstract
Regulatory T cells (Tregs) and T helper 17 (Th17) cells contribute to cancer progression and prognosis. However, regulatory factors associated with Tregs–Th17 balance were not completely understood. We previously demonstrated an immune-modulatory capacity by Notch signaling inactivation to reverse Tregs–Th17 disequilibrium in chronic hepatitis C. Thus, the aim of current study was to assess the role of Notch signaling in modulation Tregs and Th17 cells function in gastric cancer (GC) patients. A total of 51 GC patients and 18 normal controls (NCs) were enrolled. Notch1 and Notch2 mRNA expressions were semiquantified by real-time polymerase chain reaction. Tregs/Th17 percentages, transcriptional factors, and cytokines production were investigated in response to the stimulation of Notch signaling inhibitor DAPT. Both Notch1 and Notch2 mRNA expressions were elevated in GC tissues and peripheral bloods in GC patients. CD4+CD25+CD127dim/− Tregs and Th17 cells percentage was also elevated in GC patients compared with in NCs. DAPT treatment did not affect frequency of either circulating Tregs or Th17 cells, however, reduced FoxP3/RORγt mRNA expression and interleukin (IL)-35/IL-17 production in purified CD4+ T cells from GC patients. Moreover, blockade of Notch signaling also inhibited the suppressive function of purified CD4+CD25+CD127dim/− Tregs from GC patients, which presented as elevation of cellular proliferation and IL-35 secretion. The current data further provided mechanism underlying Tregs–Th17 balance in GC patients. The link between Notch signaling and Th cells might lead to a new therapeutic target for GC patients.