bluuebunny/crossref_metadata_2025_split huggingface dataset:
Logical modelling reveals the PDC-PDK interaction as the regulatory switch driving metabolic flexibility at the cellular level
Authors: Tareen Samar HK , Kutmon Martina , Arts Ilja CW , de Kok Theo M , Evelo Chris T , Adriaens Michiel E 
Published: September 2019

Abstract

Background
Metabolic flexibility is the ability of an organism to switch between substrates for energy metabolism, in response to the changing nutritional state and needs of the organism. On the cellular level, metabolic flexibility revolves around the tricarboxylic acid cycle by switching acetyl coenzyme A production from glucose to fatty acids and vice versa. In this study, we modelled cellular metabolic flexibility by constructing a logical model connecting glycolysis, fatty acid oxidation, fatty acid synthesis and the tricarboxylic acid cycle, and then using network analysis to study the behaviours of the model.

Results
We observed that the substrate switching usually occurs through the inhibition of pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinases (PDK), which moves the metabolism from glycolysis to fatty acid oxidation. Furthermore, we were able to verify four different regulatory models of PDK to contain known biological observations, leading to the biological plausibility of all four models across different cells and conditions.

Conclusion
These results suggest that the cellular metabolic flexibility depends upon the PDC-PDK regulatory interaction as a key regulatory switch for changing metabolic substrates.
Origin and diversification of Xanthomonas citri subsp. citri pathotypes revealed by inclusive phylogenomic, dating, and biogeographic analyses
Authors: Patané José S. L. , Martins Joaquim , Rangel Luiz Thiberio , Belasque José , Digiampietri Luciano A. , Facincani Agda Paula , Ferreira Rafael Marini , Jaciani Fabrício José , Zhang Yunzeng , Varani Alessandro M. , Almeida Nalvo F. , Wang Nian , Ferro Jesus A. , Moreira Leandro M. , Setubal João C. 
Published: September 2019

AbstractBackgroundXanthomonas citrisubsp.citripathotypes cause bacterial citrus canker, being responsible for severe agricultural losses worldwide. The A pathotype has a broad host spectrum, while A* and Aware more restricted both in hosts and in geography. Two previous phylogenomic studies led to contrasting well-supported clades for sequenced genomes of these pathotypes. No extensive biogeographical or divergence dating analytic approaches have been so far applied to available genomes.ResultsBased on a larger sampling of genomes than in previous studies (including six new genomes sequenced by our group, adding to a total of 95 genomes), phylogenomic analyses resulted in different resolutions, though overall indicating that A + AWis the most likely true clade. Our results suggest the high degree of recombination at some branches and the fast diversification of lineages are probable causes for this phylogenetic blurring effect. One of the genomes analyzed,X. campestrispv.durantae, was shown to be an A* strain; this strain has been reported to infect a plant of the family Verbenaceae, though there are no reports of anyX. citrisubsp.citripathotypes infecting any plant outside the Citrus genus. Host reconstruction indicated the pathotype ancestor likely had plant hosts in the family Fabaceae, implying an ancient jump to the current Rutaceae hosts. Extensive dating analyses indicated that the origin ofX. citrisubsp.citrioccurred more recently than the main phylogenetic splits of Citrus plants, suggesting dispersion rather than host-directed vicariance as the main driver of geographic expansion. An analysis of 120 pathogenic-related genes revealed pathotype-associated patterns of presence/absence.ConclusionsOur results provide novel insights into the evolutionary history ofX. citrisubsp.citrias well as a sound phylogenetic foundation for future evolutionary and genomic studies of its pathotypes.
Transcriptome changes reveal the genetic mechanisms of the reproductive plasticity of workers in lower termites
Authors: Ye Chenxu , Rasheed Humaira , Ran Yuehua , Yang Xiaojuan , Xing Lianxi , Su Xiaohong 
Published: September 2019

Abstract

Background
The reproductive plasticity of termite workers provides colonies with tremendous flexibility to respond to environmental changes, which is the basis for evolutionary and ecological success. Although it is known that all colony members share the same genetic background and that differences in castes are caused by differences in gene expression, the pattern of the specific expression of genes involved in the differentiation of workers into reproductives remains unclear. In this study, the isolated workers of Reticulitermes labralis developed into reproductives, and then comparative transcriptomes were used for the first time to reveal the molecular mechanisms underlying the reproductive plasticity of workers.

Results
We identified 38,070 differentially expressed genes and found a pattern of gene expression involved in the differentiation of the workers into reproductives. 12, 543 genes were specifically upregulated in the isolated workers. Twenty-five signal transduction pathways classified into environmental information processing were related to the differentiation of workers into reproductives. Ras functions as a signalling switch regulates the reproductive plasticity of workers. The catalase gene which is related to longevity was up-regulated in reproductives.

Conclusion
We demonstrate that workers leaving the natal colony can induce the expression of stage-specific genes in the workers, which leads to the differentiation of workers into reproductives and suggests that the signal transduction along the Ras-MAPK pathway crucially controls the reproductive plasticity of the workers. This study also provides an important model for revealing the molecular mechanism of longevity changes.
Benchmarking variant identification tools for plant diversity discovery
Authors: Wu Xing , Heffelfinger Christopher , Zhao Hongyu , Dellaporta Stephen L. 
Published: September 2019

Abstract

Background
The ability to accurately and comprehensively identify genomic variations is critical for plant studies utilizing high-throughput sequencing. Most bioinformatics tools for processing next-generation sequencing data were originally developed and tested in human studies, raising questions as to their efficacy for plant research. A detailed evaluation of the entire variant calling pipeline, including alignment, variant calling, variant filtering, and imputation was performed on different programs using both simulated and real plant genomic datasets.

Results
A comparison of SOAP2, Bowtie2, and BWA-MEM found that BWA-MEM was consistently able to align the most reads with high accuracy, whereas Bowtie2 had the highest overall accuracy. Comparative results of GATK HaplotypCaller versus SAMtools mpileup indicated that the choice of variant caller affected precision and recall differentially depending on the levels of diversity, sequence coverage and genome complexity. A cross-reference experiment of S. lycopersicum and S. pennellii reference genomes revealed the inadequacy of single reference genome for variant discovery that includes distantly-related plant individuals. Machine-learning-based variant filtering strategy outperformed the traditional hard-cutoff strategy resulting in higher number of true positive variants and fewer false positive variants. A 2-step imputation method, which utilized a set of high-confidence SNPs as the reference panel, showed up to 60% higher accuracy than direct LD-based imputation.

Conclusions
Programs in the variant discovery pipeline have different performance on plant genomic dataset. Choice of the programs is subjected to the goal of the study and available resources. This study serves as an important guiding information for plant biologists utilizing next-generation sequencing data for diversity characterization and crop improvement.
Forecasting maldistribution of human resources for healthcare and patients in Japan: a utilization-based approach
Authors: Ishikawa Tomoki , Nakao Yuji , Fujiwara Kensuke , Suzuki Teppei , Tsuji Shintaro , Ogasawara Katsuhiko 
Published: September 2019

Abstract

Background
Hokkaido’s demographic trend of population decrease with aging population is remarkable even in Japan. Although healthcare policy decision-makers need to appropriately allocate resources while grasping regional demands, not much is available on whether medical demand would increase or not for future. In addition, little is known about what impact will current situation have on future demand-supply balance and equality by regions. This study aims to support decision-making in human resource planning for coping with changing population structure by forecasting future demand, and evaluation those regional maldistributions.

Method
We set patients with acute myocardial infarction or cerebral stroke, and all medical care as study subjects and analyzed for 2015, 2025, and 2035 in Hokkaido and each Secondary Medical Care Area. We used a utilization-based approach to estimate the healthcare supply–demand balance in the future. Moreover, we evaluated the regional maldistribution of demand-supply balance by calculating Herfindahl-Hirschman Index, Gini Coefficients, the number of physicians/specialists per patient. Moreover, we conducted sensitivity analysis to evaluation impact on aspects of demand-supply balance by uncertainty of utilization for future.

Results
Our results displayed that concentration of patients will progress, while regional distribution will shrink in all subject. However, from comparison based on all medical care, Gini Coefficients of acute myocardial infarction and cerebral stroke has always been high. This suggest that the resource allocation of them has room for improvement. In addition, our analysis showed the change in this balance will differ in each region in the future. Moreover, demographic change will not consistent with the number of patient change from 2015 to 2035.

Conclusion
These results suggest policy planners should use the number of patient by disease, by region as indicator of demand, instead of provider-to-population ratios being in use today. The result of our sensitivity analysis show two findings. First, the range of each indicator have possible for future. Second, increase of utilization, for instance lowing barrier in the use by development operation of patient transportation in AMI/CS, would improve maldistribution of opportunity for resident to get emergency medical services.
Ventricular Zone Expressed PH Domain Containing 1 (VEPH1): an adaptor protein capable of modulating multiple signaling transduction pathways during normal and pathological development
Authors: Brown Theodore J. , Kollara Alexandra , Shathasivam Premalatha , Ringuette Maurice J. 
Published: September 2019

AbstractVentricular Zone Expressed PH Domain-Containing 1 (VEPH1) is an 833-amino acid protein encoded by an evolutionarily conserved single-copy gene that emerged with pseudocoelomates. This gene has no paralog in any species identified to date and few studies have investigated the function of its encoded protein. Loss of expression of its ortholog, melted, inDrosophilaresults in a severe neural phenotype and impacts TOR, FoxO, and Hippo signaling. Studies in mammals indicate a role for VEPH1 in modulating TGFβ signaling and AKT activation, while numerous studies indicate VEPH1 expression is altered in several pathological conditions, including cancer. Although often referred to as an uncharacterized protein, available evidence supports VEPH1 as an adaptor protein capable of modulating multiple signal transduction networks. Further studies are required to define these adaptor functions and the role of VEPH1 in development and disease progression.
Evaluation of median urinary iodine concentration cut-off for defining iodine deficiency in pregnant women after a long term USI in China
Authors: Zhang Huidi , Wu Meng , Yang Lichen , Wu Jinghuan , Hu Yichun , Han Jianhua , Gu Yunyou , Li Xiuwei , Wang Haiyan , Ma Liangkun , Yang Xiaoguang 
Published: September 2019

AbstractBackgroundThe WHO/UNICEF/ICCIDD define iodine deficiency during pregnancy as median urinary iodine concentration (MUIC) ≤ 150 μg/L. China implemented universal salt iodization (USI) in 1995, and recent surveillance showed nationwide elimination of iodine deficiency disorders (IDD). Data from 2014 showed that the MUIC in 19,500 pregnant women was 154.6 μg/L and 145 μg/L in 9000 pregnant women in 2015. However, symptoms of iodine deficiency were absent. Our study sought to evaluate whether MUIC below 150 μg/L affects thyroid function of Chinese pregnant women and their newborns in Chinese context.MethodsWe screened 103 women with normal thyroid function and MUIC lower than 150 μg/L during week 6 of pregnancy at Peking Union Medical College Hospital. Patient demographics and dietary salt intake were recorded. Subjects were followed at 12, 24, and 32 gestational weeks. At each visit, a 3-day dietary record, drinking water samples, and edible salt samples were collected and analyzed for total dietary iodine intake. Additionally, 24-h urine iodine and creatinine were measured. Blood tests assessed thyroid function in both mothers and newborns.ResultsOf 103 pregnant women enrolled, 79 completed all follow-up visits. Most subjects maintained normal thyroid function throughout pregnancy. However, 19 had thyroid dysfunction based on thyroid stimulating hormone and free thyroxine levels. The median serum iodine was 71 μg/L (95% CI: 44, 109). The median thyroglobulin was < 13 μg/L. values above this level indicate iodine deficiency in pregnant women. The median dietary iodine intake during pregnancy, derived from the 3-day record and measures of water and salt, was 231.17 μg/d. Assuming 90% urinary iodine excretion (UIE), 200.11 μg/d UIE means the 222.34 μg iodine loss per day, suggesting that subjects had a positive iodine balance throughout pregnancy. All neonatal blood samples showed TSH levels lower than 10 mIU/L, indicating normal thyroid function. No significant difference was found among gestational weeks for urinary iodine, and the MUIC in subjects who completed 3 follow-up visits was 107.41 μg/L.ConclusionTwenty years after implementing USI, expectant Chinese mothers with MUIC of 107.4 μg/L, less than the WHO’s 150 μg/L benchmark, maintained thyroid function in both themselves and their newborn babies.
Cancer-associated adipocytes: key players in breast cancer progression
Authors: Wu Qi , Li Bei , Li Zhiyu , Li Juanjuan , Sun Si , Sun Shengrong 
Published: September 2019

Abstract
Adipocytes are one of the primary stromal cells in many tissues, and they are considered to play an active role in the tumor microenvironment. Cancer-associated adipocytes (CAAs) are not only found adjacent to cancer cells, but also communicate with cancer cells through releasing various factors that can mediate local and systemic effects. The adipocyte-cancer cell crosstalk leads to phenotypical and functional changes of both cell types, which can further enhance tumor progression. Indeed, obesity, which is associated with an increase in adipose mass and an alteration of adipose tissue, is becoming pandemic in some countries and it is now considered to be an independent risk factor for cancer progression. In this review, we focus on the potential mechanisms involved with special attention to the adipocyte-cancer cell circle in breast cancer. We envisage that besides having a direct impact on tumor cells, CAAs systemically preconditions the tumor microenvironment by favoring anti-tumor immunity. A better understanding of cancer-associated adipocytes and the key molecular events in the adipocyte-cancer cell crosstalk will provide insights into tumor biology and permit the optimization of therapeutic strategies.
Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma
Authors: Yu Bo , Liu Delong 
Published: September 2019

AbstractAntibody-drug conjugates (ADC) represent a distinct family of chemoimmunotherapy agents. ADCs are composed of monoclonal antibodies conjugated to cytotoxic payloads via specialized chemical linkers. ADCs therefore combine the immune therapy with targeted chemotherapy. Due to the distinct biomarkers associated with lymphocytes and plasma cells, ADCs have emerged as a promising treatment option for lymphoid malignancies and multiple myeloma. Several ADCs have been approved for clinical applications: brentuximab vedotin, inotuzumab ozogamicin, moxetumomab pasudotox, and polatuzumab vedotin. More novel ADCs are under clinical development. In this article, we summarized the general principles for ADC design, and updated novel ADCs under various stages of clinical trials for lymphoid malignancies and multiple myeloma.
Comparative outcomes of foot cast and short leg cast in pseudo‐Jones avulsion fracture: a single blinded randomized controlled trial
Authors: Piyapittayanun Peerapong , Mutthakalin Kanakij , Arirachakaran Alisara , Kongtharvonskul Jatupon 
Published: September 2019

AbstractBackgroundFractures of the metatarsal bones account for 35% of all foot fractures. Conservative management of fractures proximal to the metaphyseal‐diaphyseal junction of the fifth metatarsal bone (pseudo‐Jones) is by protected weight bearing. The methods of protected weight bearing include short‐leg casting and splinting (boot cast, Jones's bandage and elastic bandage). However, currently there is no consensus as to which method is the most suitable.MethodWe have conducted a randomized controlled trial to compare outcomes of foot casting (FC) and short leg casting (SLC) to assess pain, function and complication outcomes for the treatment of pseudo‐jones metatarsal fractures. This single‐center, single blind, randomized controlled trial was conducted between 1 June 2016–1 July 2018 at Police General Hospital, Bangkok, Thailand.ResultA total of 72 pseudo‐jones metatarsal fracture participants were randomly allocated to treatment by foot cast or short leg cast. The primary outcomes were pain VAS, AOFAS and complications measured at 2, 4, 6 and 8 weeks after receiving the treatment. Seventy‐two patients (36 paticipants per group) were enrolled to receive either FC or SLC. The mean VAS measured at baseline, 2 weeks, 4 weeks, 6 weeks and 8 weeks were 7.36, 1.97, 0.58, 0.17 and 0.08 respectively in the FC group; and 6.09, 2.91, 1.23, 0.37 and 0.11 respectively in the SLC group. The mean AOFAS at baseline, 2, 4, 6 and 8 weeks were 33.60, 68.22, 82.72, 91.75 and 98.11 respectively in the FC group; and 32.60, 60.20, 70.20, 92.24 and 99.13 in the SLC group. The estimated mean difference of pain VAS and AOFAS at 2 weeks and 4 weeks were − 0.94 (95% CI: − 1.53, − 0.34), − 0.65 (95%CI: − 1.24, − 0.05), 8.02 (95%CI: 3.74, 12.10) and 12.52 (95%CI: 8.27, 16.78), which were statistically significantly better in the FC groups when compared to the SLC groups. However, there were no statistically significant difference between the two groups at 6 and 8 weeks.ConclusionThis study demonstrated that the application of foot casting can improve pain VAS and AOFAS function at 2 and 4 weeks in the treatment of pseudo‐jones metatarsal fractures when compared to short leg casting. However, at 6 and 8 weeks, there were no statistically significantly different between the two groups.
A family pedigree of malignancies associated with BRCA1 pathogenic variants: a reflection of the state of art in China
Authors: Li Wenhui , Li Lei , Wu Ming 
Published: September 2019

Abstract

Background
Little is known about the status of genetic counseling for ovarian cancer in China.

Case presentation
We report a four-generation Chinese family with several types of cancer. The proband was a patient with high-grade serous ovarian cancer (HGSOC) who was found to harbor a pathogenic BRCA1 variant. Cosegregation analysis identified 7 of 9 relatives with the same deleterious variant. One month after the genetic test, one female carrier 54 years of age was diagnosed with stage IVB HGSOC, and another female 55 years of age accepted risk-reducing salpingo-oophorectomy, which revealed occult cancer of the fallopian tube (Stage IA).

Conclusions
Genetic counseling and testing for ovarian cancer in China have fallen behind international trends. Innovative studies and practices are urgently needed to establish models for cancer screening, prevention and treatment.
Modular pathway engineering of key precursor supply pathways for lacto-N-neotetraose production in Bacillus subtilis
Authors: Dong Xiaomin , Li Nan , Liu Zhenmin , Lv Xueqin , Li Jianghua , Du Guocheng , Wang Miao , Liu Long 
Published: September 2019

Abstract

Background
Lacto-N-neotetraose (LNnT) is one of the important ingredients of human milk oligosaccharides, which can enhance immunity, regulate intestinal bacteria and promote cell maturation.

Results
In this study, the synthetic pathway of LNnT was constructed by co-expressing the lactose permease (LacY) β-1,3-N-acetylglucosaminyltransferase (LgtA) and β-1,4-galactostltransferase (LgtB) in Bacillus subtilis, resulting in an LNnT titer of 0.61 g/L. Then, by fine-tuning the expression level of LgtB, the growth inhibition was reduced and the LNnT titer was increased to 1.31 g/L. In addition, by modular pathway engineering, the positive-acting enzymes of the UDP-GlcNAc and UDP-Gal pathways were strengthened to balance the two key precursors supply, and the LNnT titer was improved to 1.95 g/L. Finally, the LNnT titer reached 4.52 g/L in a 3-L bioreactor with an optimal glucose and lactose feeding strategy.

Conclusions
In general, this study showed that the LNnT biosynthesis could be significantly increased by optimizing enzymes expression levels and modular pathway engineering for balancing the precursors supply in B. subtilis.
Asymptomatic pharyngeal carriage rate of Streptococcus pyogenes, its associated factors and antibiotic susceptibility pattern among school children in Hawassa town, southern Ethiopia
Authors: Anja Asrat , Beyene Getenet , S/Mariam Zewdineh , Daka Deresse 
Published: September 2019

AbstractObjectivesThe aim of this study was to determine the asymptomatic pharyngeal carriage rate ofS. pyogenes, antimicrobial pattern and related risk factors among school children in Hawassa, southern Ethiopia.ResultsOut of 287 school children’s screened, 35 (12.2%) were colonized withS. pyogenes. The carriage rate was significantly associated with factors such as sex (female p = 0.013) occupational status of mother (p = 0.002), lower income source (500–900 ETB, 1000–1500 ETB) (p = 0.001, and p = 0.042), history of hospitalization (p = 0.00) and residence of the children (p = 0.002). High level resistant to tetracycline and low level to vancomycin were observed, while penicillin, amoxicillin, erythromycin, chloramphenicol, and ceftriaxone were found to be effective.
Stochastic bifurcation analysis in Brusselator system with white noise
Authors: Li Changzhao , Zhang Juan 
Published: September 2019

Abstract
In this paper, we mainly study the stochastic stability and stochastic bifurcation of Brusselator system with multiplicative white noise. Firstly, by a polar coordinate transformation and a stochastic averaging method, the original system is transformed into an Itô averaging diffusion system. Secondly, we apply the largest Lyapunov exponent and the singular boundary theory to analyze the stochastic local and global stability. Thirdly, by means of the properties of invariant measures, the stochastic dynamical bifurcations of stochastic averaging Itô diffusion equation associated with the original system is considered. And we investigate the phenomenological bifurcation by analyzing the associated Fokker–Planck equation. We will show that, from the view point of random dynamical systems, the noise “destroys” the deterministic stability. Finally, an example is given to illustrate the effectiveness of our analyzing procedure.