bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary Dynamics Do Not Motivate a Single-Mutant Theory of Human Language
Authors: de Boer Bart , Thompson Bill , Ravignani Andrea , Boeckx Cedric
Published: January 2020

One of the most controversial hypotheses in cognitive science is the Chomskyan evolutionary conjecture that language arose instantaneously in humans through a single mutation. Here we analyze the evolutionary dynamics implied by this hypothesis, which has never been formalized before. The hypothesis supposes the emergence and fixation of a single mutant (capable of the syntactic operationMerge) during a narrow historical window as a result of frequency-independent selection under a huge fitness advantage in a population of an effective size no larger than ~15 000 individuals. We examine this proposal by combining diffusion analysis and extreme value theory to derive a probabilistic formulation of its dynamics. We find that although a macro-mutation is much more likely to go to fixation if it occurs, it is much more unlikelya priorithan multiple mutations with smaller fitness effects. The most likely scenario is therefore one where a medium number of mutations with medium fitness effects accumulate. This precise analysis of the probability of mutations occurring and going to fixation has not been done previously in the context of the evolution of language. Our results cast doubt on any suggestion that evolutionary reasoning provides an independent rationale for a single-mutant theory of language.
Corruption of the Pearson correlation coefficient by measurement error and its estimation, bias, and correction under different error models
Authors: Saccenti Edoardo , Hendriks Margriet H. W. B. , Smilde Age K.
Published: January 2020

Correlation coefficients are abundantly used in the life sciences. Their use can be limited to simple exploratory analysis or to construct association networks for visualization but they are also basic ingredients for sophisticated multivariate data analysis methods. It is therefore important to have reliable estimates for correlation coefficients. In modern life sciences, comprehensive measurement techniques are used to measure metabolites, proteins, gene-expressions and other types of data. All these measurement techniques have errors. Whereas in the old days, with simple measurements, the errors were also simple, that is not the case anymore. Errors are heterogeneous, non-constant and not independent. This hampers the quality of the estimated correlation coefficients seriously. We will discuss the different types of errors as present in modern comprehensive life science data and show with theory, simulations and real-life data how these affect the correlation coefficients. We will briefly discuss ways to improve the estimation of such coefficients.
Phylogenetic informativeness analyses to clarify past diversification processes in Cucurbitaceae
Authors: Bellot Sidonie , Mitchell Thomas C. , Schaefer Hanno
Published: January 2020

Phylogenomic studies have so far mostly relied on genome skimming or target sequence capture, which suffer from representation bias and can fail to resolve relationships even with hundreds of loci. Here, we explored the potential of phylogenetic informativeness and tree confidence analyses to interpret phylogenomic datasets. We studied Cucurbitaceae because their small genome size allows cost-efficient genome skimming, and many relationships in the family remain controversial, preventing inferences on the evolution of characters such as sexual system or floral morphology. Genome skimming and PCR allowed us to retrieve the plastome, 57 single copy nuclear genes, and the nuclear ribosomal ITS from 29 species representing all but one tribe of Cucurbitaceae. Node support analyses revealed few inter-locus conflicts but a pervasive lack of phylogenetic signal among plastid loci, suggesting a fast divergence of Cucurbitaceae tribes. Data filtering based on phylogenetic informativeness and risk of homoplasy clarified tribe-level relationships, which support two independent evolutions of fringed petals in the family. Our study illustrates how formal analysis of phylogenomic data can increase our understanding of past diversification processes. Our data and results will facilitate the design of well-sampled phylogenomic studies in Cucurbitaceae and related families.
Endogenous and artificial miRNAs explore a rich variety of conformations: a potential relationship between secondary structure and biological functionality
Authors: Gangemi C. M. A. , Alaimo S. , Pulvirenti A. , García-Viñuales Sara , Milardi D. , Falanga A. P. , Fragalà M. E. , Oliviero G. , Piccialli G. , Borbone N. , Ferro A. , D’Urso A. , Croce C. M. , Purrello R.
Published: January 2020

Mature microRNAs are short non-coding RNA sequences which upon incorporation into the RISC ribonucleoprotein complex, play a crucial role in regulation of gene expression. However, miRNAs can exist within the cell also as free molecules fulfilling their biological activity. Therefore, it is emerging that in addition to sequence even the structure adopted by mature miRNAs might play an important role to reach the target. Indeed, we analysed by several spectroscopic techniques the secondary structures of two artificial miRNAs selected by computational tool (miR-Synth) as best candidates to silence c-MET and EGFR genes and of two endogenous miRNAs (miR-15a and miR-15b) having the same seed region, but different biological activity. Our results demonstrate that both endogenous and artificial miRNAs can arrange in several 3D-structures which affect their activity and selectivity toward the targets.
HDAC10 deletion promotes Foxp3+ T-regulatory cell function
Authors: Dahiya Satinder , Beier Ulf H. , Wang Liqing , Han Rongxiang , Jiao Jing , Akimova Tatiana , Angelin Alessia , Wallace Douglas C. , Hancock Wayne W.
Published: January 2020

Foxp3+ T-regulatory (Treg) cells are capable of suppressing immune responses. Lysine acetylation is a key mechanism of post-translational control of various transcription factors, and when acetylated, Foxp3 is stabilized and transcriptionally active. Therefore, understanding the roles of various histone/protein deacetylases (HDAC) are key to promoting Treg-based immunotherapy. Several of the 11 classical HDAC enzymes are necessary for optimal Treg function while others are dispensable. We investigated the effect of HDAC10 in murine Tregs. HDAC10 deletion had no adverse effect on the health of mice, which retained normal CD4+ and CD8+ T cell function. However, HDAC10−/− Treg exhibited increased suppressive function in vitro and in vivo. C57BL/6 Rag1−/− mice adoptively transferred with HDAC10−/− but not wild Treg, were protected from developing colitis. HDAC10−/− but not wild-type mice receiving fully MHC-mismatched cardiac transplants became tolerant and showed long-term allograft survival (>100 d). We conclude that targeting of HDAC10 may be of therapeutic value for inflammatory disorders including colitis and also for transplantation.
Entanglement Detection via Direct-Sum Majorization Uncertainty Relations
Authors: Wang Kun , Wu Nan , Song Fangmin
Published: January 2020

In this paper we investigate the relationship between direct-sum majorization formulation of uncertainty relations and entanglement, for the case of two observables. Our primary results are entanglement detection methods based on direct-sum majorization uncertainty relations. These detectors provide a set of sufficient conditions for detecting entanglement whose number grows linearly with the dimension of the state being detected.
White matter microstructural changes in tuberous sclerosis: Evaluation by neurite orientation dispersion and density imaging (NODDI) and diffusion tensor images
Authors: Taoka Toshiaki , Aida Noriko , Fujii Yuta , Ichikawa Kazushi , Kawai Hisashi , Nakane Toshiki , Ito Rintaro , Naganawa Shinji
Published: January 2020

Neurite orientation dispersion and density imaging (NODDI) is a novel diffusion method for evaluating tissue microstructure, and may provide additional information over conventional diffusion tensor imaging (DTI). We evaluated NODDI and DTI parameters in cases of tuberous sclerosis (TS) to assess microstructural changes in the white matter. Eleven cases of tuberous sclerosis and eight age-matched controls underwent NODDI and DTI. We performed qualitative analysis and tract-based spatial statistics (TBSS) analysis of the NODDI parameters (Ficv: intracellular volume fraction, Fiso: isotropic fraction, ODI: orientation dispersion index) as well as DTI parameters (MD: mean diffusivity, FA: fractional anisotropy). We also performed a correlation analysis between clinical symptoms and parameters. The qualitative analysis indicated that the Ficv had a lower value in TS cases particularly in the tubers adjacent to the white matter. The TBSS analysis showed that the TS cases had decreased Ficv in a greater area compared to the other parameters including MD. In particular, the Ficv was decreased in deep white matter, such as the superior longitudinal fascicles (SLF). The application of NODDI to TS cases revealed tissue microstructural changes, and particularly the Ficv could detect more widespread abnormalities in white matter structure compared to DTI parameters.
Landscape of transcriptome variations uncovering known and novel driver events in colorectal carcinoma
Authors: Pira Giovanna , Uva Paolo , Scanu Antonio Mario , Rocca Paolo Cossu , Murgia Luciano , Uleri Elena , Piu Claudia , Porcu Alberto , Carru Ciriaco , Manca Alessandra , Persico Ivana , Muroni Maria Rosaria , Sanges Francesca , Serra Caterina , Dolei Antonia , Angius Andrea , De Miglio Maria Rosaria
Published: January 2020

We focused on an integrated view of genomic changes in Colorectal cancer (CRC) and distant normal colon tissue (NTC) to test the effectiveness of expression profiling on identification of molecular targets. We performed transcriptome on 16 primary coupled CRC and NTC tissues. We identified pathways and networks related to pathophysiology of CRC and selected potential therapeutic targets. CRC cells have multiple ways to reprogram its transcriptome: a functional enrichment analysis in 285 genes, 25% mutated, showed that they control the major cellular processes known to promote tumorigenesis. Among the genes showing alternative splicing, cell cycle related genes were upregulated (CCND1, CDC25B, MCM2, MCM3), while genes involved in fatty acid metabolism (ACAAA2, ACADS, ACAT1, ACOX, CPT1A, HMGCS2) were downregulated. Overall 148 genes showed differential splicing identifying 17 new isoforms. Most of them are involved in the pathogenesis of CRC, although the functions of these variants remain unknown. We identified 2 in-frame fusion events, KRT19-KRT18 and EEF1A1-HSP90AB1, encoding for chemical proteins in two CRC patients. We draw a functional interactome map involving integrated multiple genomic features in CRC. Finally, we underline that two functional cell programs are prevalently deregulated and absolutely crucial to determinate and sustain CRC phenotype.
Metabolomics Reveals that Cysteine Metabolism Plays a Role in Celastrol-Induced Mitochondrial Apoptosis in HL-60 and NB-4 Cells
Authors: Chen Minjian , Yang Jing , Li Lei , Hu Yanhui , Lu Xiaomei , Sun Rongli , Wang Yubang , Wang Xinru , Zhang Xiaoling
Published: January 2020

Recently, celastrol has shown great potential for inducing apoptosis in acute myeloid leukemia cells, especially acute promyelocytic leukaemia cells. However, the mechanism is poorly understood. Metabolomics provides an overall understanding of metabolic mechanisms to illustrate celastrol's mechanism of action. We treated both nude mice bearing HL-60 cell xenografts in vivo and HL-60 cells as well as NB-4 cells in vitro with celastrol. Ultra-performance liquid chromatography coupled with mass spectrometry was used for metabolomics analysis of HL-60 cells in vivo and for targeted L-cysteine analysis in HL-60 and NB-4 cells in vitro. Flow cytometric analysis was performed to assess mitochondrial membrane potential, reactive oxygen species and apoptosis. Western blotting was conducted to detect the p53, Bax, cleaved caspase 9 and cleaved caspase 3 proteins. Celastrol inhibited tumour growth, induced apoptosis, and upregulated pro-apoptotic proteins in the xenograft tumour mouse model. Metabolomics showed that cysteine metabolism was the key metabolic alteration after celastrol treatment in HL-60 cells in vivo. Celastrol decreased L-cysteine in HL-60 cells. Acetylcysteine supplementation reversed reactive oxygen species accumulation and apoptosis induced by celastrol and reversed the dramatic decrease in the mitochondrial membrane potential and upregulation of pro-apoptotic proteins in HL-60 cells. In NB-4 cells, celastrol decreased L-cysteine, and acetylcysteine reversed celastrol-induced reactive oxygen species accumulation and apoptosis. We are the first to identify the involvement of a cysteine metabolism/reactive oxygen species/p53/Bax/caspase 9/caspase 3 pathway in celastrol-triggered mitochondrial apoptosis in HL-60 and NB-4 cells, providing a novel underlying mechanism through which celastrol could be used to treat acute myeloid leukaemia, especially acute promyelocytic leukaemia.
Analysis of histological and microRNA profiles changes in rabbit skin development
Authors: Ding Haisheng , Cheng Guanglong , Leng Jianjian , Yang Yongxin , Zhao Xiaowei , Wang Xiaofei , Qi Yunxia , Huang Dongwei , Zhao Huiling
Published: January 2020

The periodic regrowth of rabbit fur is economically important. Here, we aimed to characterise the histological traits and microRNA (miRNA) expression profiles in the skin tissue of Wan Strain Angora rabbits at different weeks after plucking. Haematoxylin-eosin staining showed that hair follicles were in the telogen phase in the first week, while they were in the anagen phase from the fourth to twenty-fourth weeks. In addition, two small RNA libraries derived from skin samples of Wan Strain Angora rabbits at telogen and anagen stages yielded over 24 million high-quality reads. Specifically, 185 miRNAs were differentially expressed between the telogen and anagen phases. The function of the differentially expressed miRNAs was explored by comparing them with known mammalian miRNAs and by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of their predicted targets. Five new functional miRNAs were validated using quantitative real-time PCR. Moreover, the fibroblast growth factor 5 (FGF5) gene was verified to be a target of conservative_NC_013672.1_9290 and conservative_NC_013675.1_10734. We investigated differential miRNA profiles between the telogen and anagen phases of the hair cycle and our findings provide a basis for future studies focusing on the mechanisms of miRNA-mediated regulation of rabbit hair follicle cycling.
The role of a new insulin-like peptide in the pearl oyster Pinctada fucata martensii
Authors: Zhang Hua , He Maoxian
Published: January 2020

Pinctada fucata martensii, is an economically important marine bivalve species cultured for seawater pearls. At present, we know little about the molecular mechanisms of the insulin signalling pathway in this oyster. Herein, we cloned and analysed an insulin-like peptide (PfILP) and its signalling pathway-related genes. We detected their expression levels in different tissues and developmental stages. Recombinant PfILP protein was produced and found to significantly increase primary mantle cell activity and induce the expression of the proliferating cell nuclear antigen (PCNA) gene. PfILP could also regulate the 293T cell cycle by stimulating the S phase and inhibiting the G1 and G2 phases. Recombinant PfILP protein induced the expression of its signalling pathway-related genes in mantle cells. In vitro co-immunoprecipitation analysis showed that PfILP interacts with PfIRR. PfILP activated expression of the pfIRR protein, and also activated the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways by stimulating phosphorylation of MAPK and AKT. Further analysis showed that PfILP up-regulated glycogen synthesis-related genes glycogen synthase kinase-3 beta (GSK-3β), protein phosphatase 1 (PP1) and glucokinase (GK) at the mRNA level, as well as the expression of the PP1 protein, and phosphorylation of GSK-3β. These results confirmed the presence of a conserved insulin-like signalling pathway in pearl oyster that is involved in cell activity, glycogen metabolism, and other physiological processes.
Synthesis and Characterization of Selenium Nanoparticles-Lysozyme Nanohybrid System with Synergistic Antibacterial Properties
Authors: Vahdati Mahsa , Tohidi Moghadam Tahereh
Published: January 2020

In the light of promising potency of selenium nanoparticles in biomedical applications, this is the first study to report the synergistic antibacterial activity of these nanoparticles and lysozyme. The nanohybrid system was prepared with various concentrations of each component. Resistance of Escherichia coli and Staphylococcus aureus was compared in the presence of individual Nano and Bio counterparts as well as the nanohybrid system. Upon interaction of SeNPs with Lysozyme, the nanohybrid system efficiently enhanced the antibacterial activity compared to the protein. Therefore, SeNPs play an important role in inhibition of bacterial growth at very low concentrations of protein; whereas very high amount of the protein is required to inhibit bacterial growth individually. On the other hand, lysozyme has also played a vital role in antibacterial property of SeNPs, inducing 100% inhibition at very low concentration of each component. Hence, presence of both nano and bio counterparts induced vital interplay in the Nanohybrid system. The aged samples also presented good stability of SeNPs both as the intact and complex form. Results of this effort highlight design of nanohybrid systems with synergistic antibacterial properties to overcome the emerging antibiotic resistance as well as to define fruitful applications in biomedicine and food safety.
Higher Ramie mosaic virus transmission efficiency by females than by males of Bemisia tabaci MED
Authors: Peng Jing , Xie Gang , Zhang Songbai , Zheng Limin , Gao Yang , Zhang Zhuo , Luo Luyun , Su Pin , Wang Dongwei , Liu Yong , Dai Liangying , Zhang Deyong
Published: January 2020

Begomoviruses can modify their transmission vector, Bemisia tabaci, to benefit their spread, although this may not always be the case. Here, the new begomovirus Ramie mosaic virus (RaMoV) and its vector B. tabaci MED, which is dominant in China and many regions of the world, were used as a model to examine direct and indirect interaction and virus transmission by B. tabaci MED of different sexes. No significant direct or indirect effects of RaMoV were observed in B. tabaci MED females, although RaMoV could shorten the life span of B. tabaci MED females by up to 4 days. A test of RaMoV transmission by different sexes of B. tabaci MED showed that there was higher virus transmission efficiency by females than males. Overall, RaMoV is transmitted by B. tabaci MED in a sex-dependent manner, and further research is needed to uncover the mechanism of the difference in RaMoV transmission by different sexes of B. tabaci.
A Place-based Assessment of Flash Flood Hazard and Vulnerability in the Contiguous United States
Authors: Khajehei Sepideh , Ahmadalipour Ali , Shao Wanyun , Moradkhani Hamid
Published: January 2020

Flash flood is among the most catastrophic natural hazards which causes disruption in the environment and societies. Flash flood is mainly initiated by intense rainfall, and due to its rapid onset (within six hours of rainfall), taking action for effective response is challenging. Building resilience to flash floods require understanding of the socio-economic characteristics of the societies and their vulnerability to these extreme events. This study provides a comprehensive assessment of socio-economic vulnerability to flash floods and investigates the main characteristics of flash flood hazard, i.e. frequency, duration, severity, and magnitude. A socio-economic vulnerability index is developed at the county level across the Contiguous United States (CONUS). For this purpose, an ensemble of social and economic variables from the US Census and the Bureau of Economic Analysis were analyzed. Then, the coincidence of socio-economic vulnerability and flash flood hazard were investigated to identify the critical and non-critical regions. Results show that the southwest U.S. experienced severe flash flooding with high magnitude, whereas the Northern Great Plains experience lower severity and frequency. Critical counties (high-vulnerable-hotspot) are mostly located in the southern and southwestern parts of the U.S. The majority of counties in the Northern Great Plains indicate a non-critical status.
GATA4/6 regulate DHH transcription in rat adrenocortical autografts
Authors: Yoshida Takashi , Takizawa Nae , Matsuda Tadashi , Yamada Hisao , Kitada Masaaki , Tanaka Susumu
Published: January 2020

Adrenal cortex autotransplantation with ACTH stimulation may be an alternative therapy for patients with bilateral adrenalectomy to avoid adrenal crisis, but its underlying mechanism has not been elucidated. Previously, we detectedDhhupregulation in rat adrenocortical autografts after transplantation. Here, we investigated potential regulators such asGata4,Gata6,SryandSox9which affectDhhtranscription in adrenocortical autografts with or without ACTH stimulation. In ACTH-stimulated autografts,Gata4andGata6were downregulated compared to control autografts. This response was linked torDhhrepression. A reporter assay using the upstream region ofrDhhand a GATA binding motif revealed thatrDhhpromoters were significantly upregulated by co-transfection withGata4orGata6or both.SryandSox9expression in autografts with or without ACTH stimulation were verified by PCR and RNAscope analyses. The ovarian differentiation factorsFoxl2andRspo1were also upregulated in the autografts.Gata4andGata6were found to be significant factors in the regulation ofrDhhexpression and could be associated with adrenocortical autograft maintenance. Gonadal primordia with bipotential testicular and ovarian functions may also be present in these autografts.
Nano-indentation reveals a potential role for gradients of cell wall stiffness in directional movement of the resurrection plant Selaginella lepidophylla
Authors: Asgari Meisam , Brulé Véronique , Western Tamara L. , Pasini Damiano
Published: January 2020

As a physical response to water loss during drought, innerSelaginella lepidophyllastems curl into a spiral shape to prevent photoirradiation damage to their photosynthetic surfaces. Curling is reversible and involves hierarchical deformation, makingS.lepidophyllaan attractive model with which to study water-responsive actuation. Investigation at the organ and tissue level has led to the understanding that the direction and extent of stem curling can be partially attributed to stiffness gradients between adaxial and abaxial stem sides at the nanoscale. Here, we examine cell wall elasticity to understand how it contributes to the overall stem curling. We compare the measured elastic moduli along the stem length and between adaxial and abaxial stem sides using atomic force microscopy nano-indentation testing. We show that changes in cortex secondary cell wall development lead to cell wall stiffness gradients from stem tip to base, and also between adaxial and abaxial stem sides. Changes in cortical cell wall morphology and secondary cell wall composition are suggested to contribute to the observed stiffness gradients.
High neutrophil-to-lymphocyte ratio predicts short survival duration in amyotrophic lateral sclerosis
Authors: Choi Seok-Jin , Hong Yoon-Ho , Kim Sung-Min , Shin Je-Young , Suh Young Ju , Sung Jung-Joon
Published: January 2020

The present study aimed to investigate the prognostic importance of the neutrophil-to-lymphocyte ratio (NLR) in patients with amyotrophic lateral sclerosis (ALS). Among 322 patients diagnosed as having definite, probable, or possible ALS at a single tertiary hospital, 194 patients were included in the final analysis. Patients were divided into three groups (T1, T2, and T3) according to the tertile of their NLR. Survival rate was significantly lower in T3 compared to the other groups (log-rank test; T1 vs. T3, p = 0.009; T2 vs. T3, p = 0.008). Median survival duration was 37.0 (24.0–56.0), 32.5 (19.5–51.2), and 22.0 (17.0–38.0) months in T1, T2, and T3, respectively. In a multivariable Cox proportional hazards regression analysis, the hazard ratio of age at onset, bulbar-onset, and NLR (T3/T1) was 1.04 (1.02–1.06, p < 0.001), 1.68 (1.10–2.57, p = 0.015), and 1.60 (1.01–2.51, p = 0.041), respectively. A high baseline NLR may serve as a useful indicator for short survival duration in patients with ALS.
Effect of weight change and lifestyle modifications on the development or remission of nonalcoholic fatty liver disease: sex-specific analysis
Authors: Yoshioka Naoki , Ishigami Masatoshi , Watanabe Yasuko , Sumi Hajime , Doisaki Masao , Yamaguchi Takeo , Ito Takanori , Ishizu Yoji , Kuzuya Teiji , Honda Takashi , Ishikawa Tetsuya , Haruta Jun-ichi , Fujishiro Mitsuhiro
Published: January 2020

The effects of changes in various lifestyle habits on nonalcoholic fatty liver disease (NAFLD) have not been well elucidated. We aimed to clarify how weight change and lifestyle modifications were associated with the development or remission of NAFLD. In this longitudinal cohort study, we reviewed the periodic health checkup data of 1,421 subjects with no causes of liver disease besides NAFLD who had received at least two health checkups between 2009 and 2018. The prevalence of NAFLD at baseline was 34.1% (484/1,421). During follow-up period (4.6 ± 2.8 years), 104 subjects developed NAFLD and 127 subjects demonstrated NAFLD remission. The frequency of NAFLD development or that of NAFLD remission significantly increased as the larger weight gain or weight loss was, respectively (both, p < 0.001). Approximately 40% of the subjects who maintained ≥ 1%/year weight loss achieved NAFLD remission. By multivariate analysis, quitting smoking were independently associated with NAFLD development (adjusted odds ratio [AOR], 2.86; 95% CI, 1.24–6.62). Subjects who quit smoking demonstrated large weight gain (≥1%/year) significantly more frequently than the other subjects (p < 0.001). In sex-specific analysis, starting to exercise was independently associated with NAFLD remission in men (AOR, 2.38; 95% CI, 1.25–4.53).
Epigenetic Ratchet: Spontaneous Adaptation via Stochastic Gene Expression
Authors: Himeoka Yusuke , Kaneko Kunihiko
Published: January 2020

Adaptation to unforeseen environmental changes is one of the most prominent features that characterize the living system. Although signal transduction and gene regulation networks evolved to adapt specific environmental conditions that they frequently experience, it is also reported that bacteria can modify their gene expression patterns to survive a huge variety of environmental conditions even without such pre-designed networks to adapt specically to each environment. Here we propose a general mechanism of cells for such “spontaneous” adaptation, on the basis of stochastic gene expression and epigenetic modication. First, a variety of gene expression states that are marginally stable states are generated by epigenetic modication. Then by taking advantage of stochastic gene expression and dilution by cellular growth, it is shown that, a gene expression pattern that achieves greater cell growth is generically selected, as conrmed by simulations and analysis of several models. The mechanism does not require any design of gene regulation networks. General relevance of the mechanism to cell biology is also discussed.
Real-time in vivo imaging of regional lung function in a mouse model of cystic fibrosis on a laboratory X-ray source
Authors: Murrie Rhiannon P. , Werdiger Freda , Donnelley Martin , Lin Yu-wei , Carnibella Richard P. , Samarage Chaminda R. , Pinar Isaac , Preissner Melissa , Wang Jiping , Li Jian , Morgan Kaye S. , Parsons David W. , Dubsky Stephen , Fouras Andreas
Published: January 2020

Most measures of lung health independently characterise either global lung function or regional lung structure. The ability to measure airflow and lung function regionally would provide a more specific and physiologically focused means by which to assess and track lung disease in both pre-clinical and clinical settings. One approach for achieving regional lung function measurement is via phase contrast X-ray imaging (PCXI), which has been shown to provide highly sensitive, high-resolution images of the lungs and airways in small animals. The detailed images provided by PCXI allow the application of four-dimensional X-ray velocimetry (4DxV) to track lung tissue motion and provide quantitative information on regional lung function. However, until recently synchrotron facilities were required to produce the highly coherent, high-flux X-rays that are required to achieve lung PCXI at a high enough frame rate to capture lung motion. This paper presents the first translation of 4DxV technology from a synchrotron facility into a laboratory setting by using a liquid-metal jet microfocus X-ray source. This source can provide the coherence required for PCXI and enough X-ray flux to image the dynamics of lung tissue motion during the respiratory cycle, which enables production of images compatible with 4DxV analysis. We demonstrate the measurements that can be captured in vivo in live mice using this technique, including regional airflow and tissue expansion. These measurements can inform physiological and biomedical research studies in small animals and assist in the development of new respiratory treatments.
Genomic inbreeding trends, influential sire lines and selection in the global Thoroughbred horse population
Authors: McGivney Beatrice A. , Han Haige , Corduff Leanne R. , Katz Lisa M. , Tozaki Teruaki , MacHugh David E. , Hill Emmeline W.
Published: January 2020

The Thoroughbred horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date (n = 10,118), including prominent stallions (n = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades (FISR2 = 0.942,P = 2.19 × 10−13;FROHR2 = 0.88,P = 1.81 × 10−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend.
Quantitative analysis of Anaplasma marginale acquisition and transmission by Dermacentor andersoni fed in vitro
Authors: Vimonish Rubikah , Johnson Wendell C. , Mousel Michelle R. , Brayton Kelly A. , Scoles Glen A. , Noh Susan M. , Ueti Massaro W.
Published: January 2020

In this study, we describe a newin vitrotick feeding system that facilitates the study of ticks and tick-borne pathogens. To optimize the system, we usedDermacentor andersoniandAnaplasma marginaleas a tick-pathogen interaction model. Ticks were fed on bovine blood containing 10-fold dilutions of the pathogen to determine the effect of dose on tick infection rate. After feeding on infected blood, ticks were transferred to uninfected blood to stimulate bacterial replication within the tick vector. During stimulation feeding, blood samples were collected daily to determine if infected ticks secreted viableA. marginale. The results demonstrated similar attachment rates between the first and second tick feeding. Tick midgut and salivary glands were infected withA. marginale. However, salivary gland infection rates decreased as the percentage of parasitized erythrocytes decreased during tick acquisition feeding. Bacteria recovered from thein vitrosystem were able to infect a naïve bovine host. Using the highly transmissibleA. marginaleSt. Maries strain, we demonstrated that the artificial tick feeding system is a suitable tool to study tick-pathogen interactions and thatA. marginaletick salivary gland infection is dose dependent. This work demonstrates the utility of an artificial tick feeding system to directly study the association between the number of acquired pathogens and transmissibility by ticks.
Design of nanoscaled heterojunctions in precursor-derived t-ZrO2/SiOC(N) nanocomposites: Transgressing the boundaries of catalytic activity from UV to visible light
Authors: Bhaskar Shakthipriya , Awin Eranezhuth Wasan , Kumar K. C. Hari , Lale Abhijeet , Bernard Samuel , Kumar Ravi
Published: January 2020

In this work, nanocomposites made of nanosized zirconia crystallized in situ in an amorphous silicon oxycarbo(nitride) (SiOC(N)) matrix have been designed through a precursor route for visible light photocatalytic applications. The relative volume fraction of the starting precursors and the pyrolysis temperatures not only influences the phase fraction of zirconia crystallites but also stabilizes the tetragonal crystal structure of zirconia (t-ZrO2) at room temperature. The presence of carbon in interstitial sites of zirconia and oxygen vacancy defects led to drastic reduction in the band gap (2.2 eV) of the nanocomposite. Apart from being a perfect host avoiding sintering of the active phase and providing mechanical stability, the amorphous matrix also reduces the recombination rate by forming heterojunctions with t-ZrO2. The reduction in band gap as well as the formation of heterojunctions aids in harnessing the visible light for photocatalytic activity.
Fam151b, the mouse homologue of C.elegans menorin gene, is essential for retinal function
Authors: Findlay Amy S. , McKie Lisa , Keighren Margaret , Clementson-Mobbs Sharon , Sanchez-Pulido Luis , Wells Sara , Cross Sally H. , Jackson Ian J.
Published: January 2020

Fam151b is a mammalian homologue of the C. elegans menorin gene, which is involved in neuronal branching. The International Mouse Phenotyping Consortium (IMPC) aims to knock out every gene in the mouse and comprehensively phenotype the mutant animals. This project identified Fam151b homozygous knock-out mice as having retinal degeneration. We show they have no photoreceptor function from eye opening, as demonstrated by a lack of electroretinograph (ERG) response. Histological analysis shows that during development of the eye the correct number of cells are produced and that the layers of the retina differentiate normally. However, after eye opening at P14, Fam151b mutant eyes exhibit signs of retinal stress and rapidly lose photoreceptor cells. We have mutated the second mammalian menorin homologue, Fam151a, and homozygous mutant mice have no discernible phenotype. Sequence analysis indicates that the FAM151 proteins are members of the PLC-like phosphodiesterase superfamily. However, the substrates and function of the proteins remains unknown.
Response of ammonia-oxidizing Bacteria and Archaea to long-term saline water irrigation in alluvial grey desert soils
Authors: Guo Huijuan , Ma Lijuan , Liang Yongchao , Hou Zhenan , Min Wei
Published: January 2020

Soil nitrification via ammonia oxidation is a key ecosystem process in terrestrial environments, but little is known of how increasing irrigation of farmland soils with saline waters effects these processes. We investigated the effects of long-term irrigation with saline water on the abundances and community structures of ammonia-oxidizing bacteria (AOB) and archaea (AOA). Irrigation with brackish or saline water increased soil salinity (EC1:5) and NH4-N compared to irrigation with freshwater, while NO3-N, potential nitrification rates (PNR) and amoA gene copy numbers of AOA and AOB decreased markedly under irrigation regimes with saline waters. Moreover, irrigation with brackish water lowered AOA/AOB ratios. PNR was positively correlated with AOA and AOB amoA gene copy numbers across treatments. Saline and brackish water irrigation significantly increased the diversity of AOA, as noted by Shannon index values, while saline water irrigation markedly reduced AOB diversity. In addition, irrigation with brackish or fresh waters resulted in higher proportions of unclassified taxa in the AOB communities. However, irrigation with saline water led to higher proportions of unclassified taxa in the AOA communities along with the Candidatus Nitrosocaldus genus, as compared to soils irrigated with freshwater. AOA community structures were closely associated with soil salinity, NO3−N, and pH, while AOB communities were only significantly associated with NO3−N and pH. These results suggest that salinity was the dominant factor affecting the growth of ammonia-oxidizing microorganisms and community structure. These results can provide a scientific basis for further exploring the response mechanism of ammonia-oxidizing microorganisms and their roles in nitrogen transformation in alluvial grey desert soils of arid areas.
POU domain motif3 (Pdm3) induces wingless (wg) transcription and is essential for development of larval neuromuscular junctions in Drosophila
Authors: Kim Yeon , Cho Kyung-Ok
Published: January 2020

Wnt is a conserved family of secreted proteins that play diverse roles in tissue growth and differentiation. Identification of transcription factors that regulate wnt expression is pivotal for understanding tissue-specific signaling pathways regulated by Wnt. We identified pdm3m7, a new allele of the pdm3 gene encoding a POU family transcription factor, in a lethality-based genetic screen for modifiers of Wingless (Wg) signaling in Drosophila. Interestingly, pdm3m7 larvae showed slow locomotion, implying neuromuscular defects. Analysis of larval neuromuscular junctions (NMJs) revealed decreased bouton number with enlarged bouton in pdm3 mutants. pdm3 NMJs also had fewer branches at axon terminals than wild-type NMJs. Consistent with pdm3m7 being a candidate wg modifier, NMJ phenotypes in pdm3 mutants were similar to those of wg mutants, implying a functional link between these two genes. Indeed, lethality caused by Pdm3 overexpression in motor neurons was completely rescued by knockdown of wg, indicating that Pdm3 acts upstream to Wg. Furthermore, transient expression of Pdm3 induced ectopic expression of wg-LacZ reporter and Wg effector proteins in wing discs. We propose that Pdm3 expressed in presynaptic NMJ neurons regulates wg transcription for growth and development of both presynaptic neurons and postsynaptic muscles.
Application of CT texture analysis to assess the localization of primary aldosteronism
Authors: Akai Hiroyuki , Yasaka Koichiro , Kunimatsu Akira , Ohtomo Kuni , Abe Osamu , Kiryu Shigeru
Published: January 2020

We performed present study to investigate whether the localization of primary aldosteronism (PA) can be predicted using quantitative texture analysis on unenhanced computed tomography (CT). Plain CT data of 82 PA patients (54 unilateral (right-sided:left-sided = 24:30), 28 bilateral) were analyzed retrospectively. After semi-automatically setting the region of interest to include the whole adrenal gland, texture analyses were performed with or without a Laplacian of Gaussian filter with various spatial scaling factors (SSFs). Logistic regression analysis was performed using the extracted histogram-based texture features to identify parameters capable of predicting excessive aldosterone production. The result of adrenal venous sampling served as gold standard in present study. As a result, logistic regression analysis indicated that the mean gray level intensity (p = 0.026), the mean value of the positive pixels (p = 0.003) in the unfiltered image, and entropy (p = 0.027) in the filtered image (SSF: 2 mm) were significant parameters. Using the model constructed by logistic regression analysis and the optimum cutoff value, the localization of PA (three multiple choices of left, right or bilateral) was determined with an accuracy of 67.1% (55/82). CT texture analysis may provide a potential avenue for less invasive prediction of the localization of PA.
Spatial Variability of Soil Properties and Portable X-Ray Fluorescence-quantified Elements of typical Golf Courses Soils
Authors: Yang Yujian , Tong Xueqin , Zhang Yingpeng
Published: January 2020

Understanding and quantitative delineation of Portable X-Ray Fluorescence (PXRF) -quantified elements and soil properties spatial variability are important for healthy turf development for golf courses. In this study, PXRF-quantified elements and soil properties (except soil acidity and alkalinity (pH), electric conductivity (EC), and textures) of 200 soil samples were measured by PXRF analyzer at different golf courses in Lubbock, Amarillo, and Midland in Texas, and Hobbs in New Mexico. Furthermore, principal component analysis (PCA), empirical bayesian kriging (EBK) and the ordinary least square model (OLSM) were used in the study. Two kinds of components were extracted and interpreted by PCA, the results showed Zn, Ti, Fe, Rb, V, Mn and Zr were associated with the component 1, while Sr was associated with the component 2, the preliminary classification of PXRF-quantified elements was formed by PCA. The EBK approach was used to evaluate the spatial patterns of PXRF-quantified elements and soil properties. The OLSM model quantitatively related pH to EC, silt texture and the PXRF-quantified K, Ca and Sr. The integration of PCA, EBK and OLSM revealed quantitative links between soil pedogenesis and causes, spatial variability and couple relationships of PXRF-quantified elements and soil properties over golf courses.
Deletion of CD2-like gene from the genome of African swine fever virus strain Georgia does not attenuate virulence in swine
Authors: Borca Manuel V. , O’Donnell Vivian , Holinka Lauren G. , Risatti Guillermo R. , Ramirez-Medina Elizabeth , Vuono Elizabeth A. , Shi Jishu , Pruitt Sarah , Rai Ayushi , Silva Ediane , Velazquez-Salinas Lauro , Gladue Douglas P.
Published: January 2020

The CD2-like African swine fever virus (ASFV) gene 8DR, (also known as EP402R) encodes for a structural transmembrane glycoprotein that has been shown to mediate hemadsorption and be involved in host immunomodulation as well as the induction of protective immune response. In addition, several natural ASFV isolates showing decreased virulence in swine has been shown to be non-hemadsorbing suggesting an association between altered or deleted forms of 8DR and virus attenuation. Here we demonstrate that deletion of 8DR gene from the genome of ASFV Georgia2010 isolate (ASFV-G-Δ8DR) does not significantly alter the virulence of the virus. ASFV-G-Δ8DR inoculated intramuscularly or intranasally (in a range of 102 to 104 TCID50) produced a clinical disease in domestic pigs indistinguishable from that induced by the same doses of the virulent parental ASFV Georgia2010 isolate. In addition, viremia values in ASFV-G-Δ8DR do not differ from those detected in animals infected with parental virus. Therefore, deletion of 8DR gene is not associated with a noticeable decrease in virulence of the ASFV Georgia isolate.
Association of serum uric acid with visceral, subcutaneous and hepatic fat quantified by magnetic resonance imaging
Authors: Rospleszcz Susanne , Dermyshi Ditjon , Müller-Peltzer Katharina , Strauch Konstantin , Bamberg Fabian , Peters Annette
Published: January 2020

Elevated serum uric acid (SUA) is associated with a variety of medical conditions, such as hypertension, diabetes and obesity. Analyses investigating uric acid and obesity were primarily conducted using anthropometric measures like BMI and waist circumference. However, different adipose tissue depots might be differentially affected in uric acid metabolism. We analyzed the relation of SUA with visceral, subcutaneous and hepatic fat as quantified by Magnetic Resonance Imaging in N = 371 individuals from a cross-sectional sample of a population-based cohort. Associations of SUA and fat depots were calculated by regressions adjusted for potential confounders. We found that SUA was correlated with all fat measures (e.g. Pearson’s r between SUA and hepatic fat: 0.50, 95%-CI: 0.42, 0.57). Associations with visceral and hepatic fat, but not with subcutaneous fat, remained evident after adjustment for anthropometric measures (e.g. visceral fat: β = 0.51 l, 95%-CI: 0.30 l, 0.72 l). In conclusion, these results show how different adipose tissue compartments are affected by SUA to varying degrees, thus emphasizing the different physiological roles of these adipose tissues in uric acid metabolism.
Sleep disturbance in Inflammatory Bowel Disease: prevalence and risk factors – A cross-sectional study
Authors: Marinelli C. , Savarino E. V. , Marsilio I. , Lorenzon G. , Gavaruzzi T. , D’Incà R. , Zingone F.
Published: January 2020

Inflammatory bowel diseases (IBD) are chronic relapsing disorders that have a negative impact on quality of life. They can be highly disabling and have been associated with sleep disturbance. The aim of our study was to evaluate the sleep quality of a large cohort of IBD patients to identify possible associated cofactors. We prospectively recruited consecutive patients attending the IBD Unit of “Azienda Ospedaliera” of Padua from November 2018 to May 2019 and collected demographics and clinical characteristics. The patients completed the Pittsburgh Sleep Quality Index (PSQI), the IBD questionnaire (IBDQ), the IBD-Disability Index (IBD-DI) questionnaire, and the Hospital Anxiety and Depression Scale (9-HADS). A multivariate regression model was applied to assess independent risk factors of sleep disturbance among IBD-related variables, disability, quality of life, anxiety, and depression. We investigated the sleep quality of 166 patients with IBD, finding 67.5% of them suffering from sleep disturbance. In particular, low quality of life, presence of disability and extraintestinal manifestations were identified as independent risk factors of sleep disturbance. We discovered that all depressed patients were also affected by sleep disturbance, while we found no difference in sleep disturbance between patients with or without anxiety state. However, a positive correlation was reported between both anxiety and depression scores and PSQI score (Spearman correlation: r = 0.31 and r = 0.38 respectively). Our study showed that sleep quality is not directly associated with an active or inactive IBD state or with the ongoing treatment, but it is mostly correlated with the patients’ mood state, disability, and quality of life. Gastroenterologists and psychologists should join forces during clinical outpatients’ visits to evaluate emotional states for a better IBD management.