bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early life home microbiome and hyperactivity/inattention in school-age children
Authors: Casas Lidia , Karvonen Anne M. , Kirjavainen Pirkka V. , Täubel Martin , Hyytiäinen Heidi , Jayaprakash Balamuralikrishna , Lehmann Irina , Standl Marie , Pekkanen Juha , Heinrich Joachim 
Published: November 2019

AbstractThis study evaluates the association between indoor microbial diversity early in life and hyperactivity/inattention symptoms in children at ages 10 and 15 years.A random sample enriched with subjects with hyperactivity/inattention at age 15 years was selected from the German LISA birth cohort. Bedroom floor dust was collected at age 3 months and 4 bacterial and fungal diversity measures [number of observed operational taxonomic units (OTUs), Chao1, Shannon and Simpson indices] were calculated from Illumina MiSeq sequencing data. Hyperactivity/inattention was based on the Strengths and Difficulties Questionnaire at ages 10 and 15 (cut-off ≥7). Adjusted associations between 4 diversity measures in tertiles and hyperactivity/inattention were investigated with weighted and survey logistic regression models. We included 226 individuals with information on microbial diversity and hyperactivity/inattention. Early life bacterial diversity was inversely associated with hyperactivity/inattention at age 10 [bacterial OTUs (medium vs low: aOR = 0.4, 95%CI = (0.2–0.8)) and Chao1 (medium vs low: 0.3 (0.1–0.5); high vs low: 0.3 (0.2–0.6)], whereas fungal diversity was directly associated [Chao1 (high vs low: 2.1 (1.1–4.0)), Shannon (medium vs low: 2.8 (1.3–5.8)), and Simpson (medium vs low: 4.7 (2.4–9.3))]. At age 15, only Shannon index was significantly associated with hyperactivity/inattention [bacteria (medium vs low: 2.3 (1.2–4.2); fungi (high vs low: 0.5 (0.3–0.9))]. In conclusion, early life exposure to microbial diversity may play a role in the psychobehavioural development. We observe heterogeneity in the direction of the associations encouraging further longitudinal studies to deepen our understanding of the characteristics of the microbial community underlying the observed associations.
2, 3-Dihydro-3β-methoxy Withaferin-A Lacks Anti-Metastasis Potency: Bioinformatics and Experimental Evidences
Authors: Chaudhary Anupama , Kalra Rajkumar S. , Malik Vidhi , Katiyar Shashank P. , Sundar Durai , Kaul Sunil C. , Wadhwa Renu 
Published: November 2019

AbstractWithaferin-A is a withanolide, predominantly present in Ashwagandha (Withania somnifera). It has been shown to possess anticancer activity in a variety of human cancer cells in vitro and in vivo. Molecular mechanism of such cytotoxicity has not yet been completely understood. Withaferin-A and Withanone were earlier shown to activate p53 tumor suppressor and oxidative stress pathways in cancer cells. 2,3-dihydro-3β-methoxy analogue of Withaferin-A (3βmWi-A) was shown to lack cytotoxicity and well tolerated at higher concentrations. It, on the other hand, protected normal cells against oxidative, chemical and UV stresses through induction of anti-stress and pro-survival signaling. We, in the present study, investigated the effect of Wi-A and 3βmWi-A on cell migration and metastasis signaling. Whereas Wi-A binds to vimentin and heterogeneous nuclear ribonucleoprotein K (hnRNP-K) with high efficacy and downregulates its effector proteins, MMPs and VEGF, involved in cancer cell metastasis, 3βmWi-A was ineffective. Consistently, Wi-A, and not 3βmWi-A, caused reduction in cytoskeleton proteins (Vimentin, N-Cadherin) and active protease (u-PA) that are essential for three key steps of cancer cell metastasis (EMT, increase in cell migration and invasion).
Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population
Authors: Low Siew-Kee , Chin Yoon Ming , Ito Hidemi , Matsuo Keitaro , Tanikawa Chizu , Matsuda Koichi , Saito Hiroko , Sakurai-Yageta Mika , Nakaya Naoki , Shimizu Atsushi , Nishizuka Satoshi S. , Yamaji Taiki , Sawada Norie , Iwasaki Motoki , Tsugane Shoichiro , Takezaki Toshiro , Suzuki Sadao , Naito Mariko , Wakai Kenji , Kamatani Yoichiro , Momozawa Yukihide , Murakami Yoshinori , Inazawa Johji , Nakamura Yusuke , Kubo Michiaki , Katagiri Toyomasa , Miki Yoshio 
Published: November 2019

AbstractGenome-wide association studies (GWAS) have successfully identified about 70 genomic loci associated with breast cancer. Owing to the complexity of linkage disequilibrium and environmental exposures in different populations, it is essential to perform regional GWAS for better risk prediction. This study aimed to investigate the genetic architecture and to assess common genetic risk model of breast cancer with 6,669 breast cancer patients and 21,930 female controls in the Japanese population. This GWAS identified 11 genomic loci that surpass genome-wide significance threshold of P < 5.0 × 10−8 with nine previously reported loci and two novel loci that include rs9862599 on 3q13.11 (ALCAM) and rs75286142 on 21q22.12 (CLIC6-RUNX1). Validation study was carried out with 981 breast cancer cases and 1,394 controls from the Aichi Cancer Center. Pathway analyses of GWAS signals identified association of dopamine receptor medicated signaling and protein amino acid deacetylation with breast cancer. Weighted genetic risk score showed that individuals who were categorized in the highest risk group are approximately 3.7 times more likely to develop breast cancer compared to individuals in the lowest risk group. This well-powered GWAS is a representative study to identify SNPs that are associated with breast cancer in the Japanese population.
Endemic foot and mouth disease: pastoral in-herd disease dynamics in sub-Saharan Africa
Authors: McLachlan I. , Marion G. , McKendrick I. J. , Porphyre T. , Handel I. G. , Bronsvoort B. M. deC. 
Published: November 2019

AbstractFoot and mouth disease (FMD) burden disproportionally affects Africa where it is considered endemic. Smallholder livestock keepers experience significant losses due to disease, but the dynamics and mechanisms underlying persistence at the herd-level and beyond remain poorly understood. We address this knowledge gap using stochastic, compartmental modelling to explore FMD virus (FMDV) persistence, outbreak dynamics and disease burden in individual cattle herds within an endemic setting. Our analysis suggests repeated introduction of virus from outside the herd is required for long-term viral persistence, irrespective of carrier presence. Risk of new disease exposures resulting in significant secondary outbreaks is reduced by the presence of immune individuals giving rise to a period of reduced risk, the predicted duration of which suggests that multiple strains of FMDV are responsible for observed yearly herd-level outbreaks. Our analysis suggests management of population turnover could potentially reduce disease burden and deliberate infection of cattle, practiced by local livestock keepers in parts of Africa, has little effect on the duration of the reduced risk period but increases disease burden. This work suggests that FMD control should be implemented beyond individual herds but, in the interim, herd management may be used to reduced FMD impact to livestock keepers.
Chemostratigraphic correlations across the first major trilobite extinction and faunal turnovers between Laurentia and South China
Authors: Lin Jih-Pai , Sundberg Frederick A. , Jiang Ganqing , Montañez Isabel P. , Wotte Thomas 
Published: November 2019

AbstractDuring Cambrian Stage 4 (~514 Ma) the oceans were widely populated with endemic trilobites and three major faunas can be distinguished: olenellids, redlichiids, and paradoxidids. The lower–middle Cambrian boundary in Laurentia was based on the first major trilobite extinction event that is known as the Olenellid Biomere boundary. However, international correlation across this boundary (the Cambrian Series 2–Series 3 boundary) has been a challenge since the formal proposal of a four-series subdivision of the Cambrian System in 2005. Recently, the base of the international Cambrian Series 3 and of Stage 5 has been named as the base of the Miaolingian Series and Wuliuan Stage. This study provides detailed chemostratigraphy coupled with biostratigraphy and sequence stratigraphy across this critical boundary interval based on eight sections in North America and South China. Our results show robust isotopic evidence associated with major faunal turnovers across the Cambrian Series 2–Series 3 boundary in both Laurentia and South China. While the olenellid extinction event in Laurentia and the gradual extinction of redlichiids in South China are linked by an abrupt negative carbonate carbon excursion, the first appearance datum of Oryctocephalus indicus is currently the best horizon to achieve correlation between the two regions.
Early change in circulating tumor DNA as a potential predictor of response to chemotherapy in patients with metastatic colorectal cancer
Authors: Osumi Hiroki , Shinozaki Eiji , Yamaguchi Kensei , Zembutsu Hitoshi 
Published: November 2019

AbstractThe impact of ctDNA changes after chemotherapy on the clinical outcomes of patients with metastatic colorectal cancer (mCRC) remains unclear. The present study evaluated the clinical implications of the early change in ctDNA levels as a predictor of objective response and clinical outcome in mCRC patients who received chemotherapy. We investigated the effects of after/before ratio of ctDNA levels 2 and 8 weeks after initiation of second-line chemotherapy, on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). ctDNA was detected using amplicon-based deep sequencing with a molecular barcode encompassing >240 hotspot mutations in 14 colon cancer-related genes. In multivariate analysis, as compared to baseline, patients with lower ctDNA level (≤50%) 8 weeks after initiation of chemotherapy showed significantly longer PFS and OS than the patients with higher (>50%) ctDNA level. In patients achieving a partial response or stable disease, the after/before ratio of ctDNA level 8 weeks after initiation of chemotherapy was significantly lower than those in patients with progressive disease. The present study suggests that an early change in the ctDNA level might serve as a biomarker to predict the chemotherapeutic efficacy and clinical outcomes in patients with mCRC.
Quantitative analysis of intracranial electrocorticography signals using the concept of statistical parametric mapping
Authors: Motoi Hirotaka , Jeong Jeong-Won , Juhász Csaba , Miyakoshi Makoto , Nakai Yasuo , Sugiura Ayaka , Luat Aimee F. , Sood Sandeep , Asano Eishi 
Published: November 2019

AbstractStatistical parametric mapping (SPM) is a technique with which one can delineate brain activity statistically deviated from the normative mean, and has been commonly employed in noninvasive neuroimaging and EEG studies. Using the concept of SPM, we developed a novel technique for quantification of the statistical deviation of an intracranial electrocorticography (ECoG) measure from the nonepileptic mean. We validated this technique using data previously collected from 123 patients with drug-resistant epilepsy who underwent resective epilepsy surgery. We determined how the measurement of statistical deviation of modulation index (MI) from the non-epileptic mean (rated by z-score) improved the performance of seizure outcome classification model solely based on conventional clinical, seizure onset zone (SOZ), and neuroimaging variables. Here, MI is a summary measure quantifying the strength of in-situ coupling between high-frequency activity at >150 Hz and slow wave at 3–4 Hz. We initially generated a normative MI atlas showing the mean and standard deviation of slow-wave sleep MI of neighboring non-epileptic channels of 47 patients, whose ECoG sampling involved all four lobes. We then calculated ‘MI z-score’ at each electrode site. SOZ had a greater ‘MI z-score’ compared to non-SOZ in the remaining 76 patients. Subsequent multivariate logistic regression analysis and receiver operating characteristic analysis to the combined data of all patients revealed that the full regression model incorporating all predictor variables, including SOZ and ‘MI z-score’, best classified the seizure outcome with sensitivity/specificity of 0.86/0.76. The model excluding ‘MI z-score’ worsened its sensitivity/specificity to 0.86/0.48. Furthermore, the leave-one-out analysis successfully cross-validated the full regression model. Measurement of statistical deviation of MI from the non-epileptic mean on invasive recording is technically feasible. Our analytical technique can be used to evaluate the utility of ECoG biomarkers in epilepsy presurgical evaluation.
Pollinator restoration in Brazilian ecosystems relies on a small but phylogenetically-diverse set of plant families
Authors: Campbell Alistair John , Gigante Carvalheiro Luísa , Gastauer Markus , Almeida-Neto Mário , Giannini Tereza Cristina 
Published: November 2019

AbstractThe alarming rate of global pollinator decline has made habitat restoration for pollinators a conservation priority. At the same time, empirical and theoretical studies on plant-pollinator networks have demonstrated that plant species are not equally important for pollinator community persistence and restoration. However, the scarcity of comprehensive datasets on plant-pollinator networks in tropical ecosystems constrains their practical value for pollinator restoration. As closely-related species often share traits that determine ecological interactions, phylogenetic relationships could inform restoration programs in data-scarce regions. Here, we use quantitative bee-plant networks from Brazilian ecosystems to test if priority plant species for different restoration criteria (bee species richness and visitation rates) can be identified using interaction networks; if phylogenetic relationships alone can guide plant species selection; and how restoration criteria influence restored network properties and function. We found plant species that maximised the benefits of habitat restoration for bees (i.e., generalists and those with distinct flower-visitor species) were clustered in a small number of phylogenetically-diverse plant families, and that prioritising the recovery of bee visitation rates improved both stability and function of restored plant-pollinator networks. Our approach can help guide restoration of pollinator communities, even where information on local ecosystems is limited.
Size increase without genetic divergence in the Eurasian water shrew Neomys fodiens
Authors: Balmori-de la Puente Alfonso , Nores Carlos , Román Jacinto , Fernández-González Angel , Aymerich Pere , Gosálbez Joaquim , Escoda Lídia , Castresana Jose 
Published: November 2019

AbstractWhen a population shows a marked morphological change, it is important to know whether that population is genetically distinct; if it is not, the novel trait could correspond to an adaptation that might be of great ecological interest. Here, we studied a subspecies of water shrew, Neomys fodiens niethammeri, which is found in a narrow strip of the northern Iberian Peninsula. This subspecies presents an abrupt increase in skull size when compared to the rest of the Eurasian population, which has led to the suggestion that it is actually a different species. Skulls obtained from owl pellets collected over the last 50 years allowed us to perform a morphometric analysis in addition to an extensive multilocus analysis based on short intron fragments successfully amplified from these degraded samples. Interestingly, no genetic divergence was detected using either mitochondrial or nuclear data. Additionally, an allele frequency analysis revealed no significant genetic differentiation. The absence of genetic divergence and differentiation revealed here indicate that the large form of N. fodiens does not correspond to a different species and instead represents an extreme case of size increase, of possible adaptive value, which deserves further investigation.
Synergies reciprocally relate end-effector and joint-angles in rhythmic pointing movements
Authors: Valk Tim A. , Mouton Leonora J. , Otten Egbert , Bongers Raoul M. 
Published: November 2019

AbstractDuring rhythmic pointing movements, degrees of freedom (DOF) in the human action system—such as joint-angles in the arm—are assumed to covary to stabilise end-effector movement, e.g. index finger. In this paper, it is suggested that the end-effector movement and the coordination of DOF are reciprocally related in synergies that link DOF so as to produce the end-effector movement. The coordination of DOF in synergies and the relation between end-effector movement and DOF coordination received little attention, though essential to understand the principles of synergy formation. Therefore, the current study assessed how the end-effector movement related to the coordination of joint-angles during rhythmic pointing across target widths and distances. Results demonstrated that joint-angles were linked in different synergies when end-effector movements differed across conditions. Furthermore, in every condition, three joint-angles (shoulder plane of elevation, shoulder inward-outward rotation, elbow flexion-extension) largely drove the end-effector, and all joint-angles contributed to covariation that stabilised the end-effector. Together, results demonstrated synergies that produced the end-effector movement, constrained joint-angles so that they covaried to stabilise the end-effector, and differed when end-effector movement differed. Hence, end-effector and joint-angles were reciprocally related in synergies—indicating that the action system was organised as a complex dynamical system.
An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells
Authors: Xavier Pedro L. P. , Cordeiro Yonara G. , Alexandre Pâmela A. , Pires Pedro R. L. , Saranholi Bruno H. , Silva Edson R. , Müller Susanne , Fukumasu Heidge 
Published: November 2019

AbstractTargeting self-renewal and tumorigenicity has been proposed as a potential strategy against cancer stem cells (CSCs). Epigenetic proteins are key modulators of gene expression and cancer development contributing to regulation and maintenance of self-renewal and tumorigenicity. Here, we have screened a small-molecule epigenetic inhibitor library using 3D in vitro models in order to determine potential epigenetic targets associated with self-renewal and tumorigenicity in Canine Mammary Cancer (CMC) cells. We identified inhibition of BET proteins as a promising strategy to inhibit CMC colonies and tumorspheres formation. Low doses of (+)-JQ1 were able to downregulate important genes associated to self-renewal pathways such as WNT, NOTCH, Hedgehog, PI3K/AKT/mTOR, EGF receptor and FGF receptor in CMC tumorspheres. In addition, we observed downregulation of ZEB2, a transcription factor important for the maintenance of self-renewal in canine mammary cancer cells. Furthermore, low doses of (+)-JQ1 were not cytotoxic in CMC cells cultured in 2D in vitro models but induced G2/M cell cycle arrest accompanied by upregulation of G2/M checkpoint-associated genes including BTG2 and CCNG2. Our work indicates the BET inhibition as a new strategy for canine mammary cancers by modulating the self-renewal phenotype in tumorigenic cells such as CSCs.
Estimation of TiO2-FeO-Na2O slag viscosity through molecular dynamics simulations for an energy efficient ilmenite smelting process
Authors: Kim Youngjae , Park Hyunsik 
Published: November 2019

AbstractAlong with the increasing demand for the TiO2 pigment, the ilmenite smelting process has also become significant because it can utilize both rock- and sand-type ilmenite. However, due to the high liquidus temperature of the TiO2 slag system, the smelting process is highly energy consuming. In the present study, the viscosity of molten ilmenite slag was estimated using molecular dynamic simulations at a high temperature to achieve an appropriate and efficient slag design. To verify the validity of the simulation technique, experimental measurements were performed in parallel and their results were compared. The effects of FeO and Na2O addition on viscosity of TiO2 slag were also investigated. The addition of Na2O as a flux enhanced the ilmenite smelting process by not only lowering the liquidus temperature but also slowing the drastic viscosity increase. Statistical information obtained from the molecular dynamic simulations revealed a three-dimensional TiO6 octahedral network structure. The relationship between viscosity and structural change with varying FeO and Na2O concentrations was explored considering the coordination number of Ti and various bonding types.
Lowering the culture temperature corrects collagen abnormalities caused by HSP47 gene knockout
Authors: Fujii Kazunori K. , Taga Yuki , Sakai Takayuki , Ito Shinya , Hattori Shunji , Nagata Kazuhiro , Koide Takaki 
Published: November 2019

AbstractHeat shock protein 47 (HSP47) is an endoplasmic reticulum (ER)-resident molecular chaperone that specifically recognizes triple helical portions of procollagens. The chaperone function of HSP47 is indispensable in mammals, and hsp47-null mice show an embryonic lethal phenotype accompanied by severe abnormalities in collagen-based tissue structures. Two leading hypotheses are currently accepted for the molecular function of HSP47 as a procollagen-specific chaperone. One is facilitation of procollagen folding by stabilizing thermally unstable triple helical folding intermediates, and the other is inhibition of procollagen aggregation or lateral association in the ER. The aim of this study was to elucidate the functional essence of this unique chaperone using fibroblasts established from hsp47−/− mouse embryos. When the cells were cultured at 37 °C, various defects in procollagen biosynthesis were observed, such as accumulation in the ER, over-modifications including prolyl hydroxylation, lysyl hydroxylation, and further glycosylation, and unusual secretion of type I collagen homotrimer. All defects were corrected by culturing the cells at a lower temperature of 33 °C. These results indicated that lowering the culture temperature compensated for the loss of HSP47. This study elucidated that HSP47 stabilizes the elongating triple helix of procollagens, which is otherwise unstable at the body temperature of mammals.