bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Arabidopsis mitochondrial dicarboxylate carrier 2 maintains leaf metabolic homeostasis by uniting malate import and citrate export
Authors: Lee Chun Pong , Elsässer Marlene , Fuchs Philippe , Fenske Ricarda , Schwarzländer Markus , Millar A. Harvey 
Published: April 2020

ABSTRACTMalate is the major substrate for respiratory oxidative phosphorylation in illuminated leaves. In the mitochondria malate is converted to citrate either for replenishing tricarboxylic acid (TCA) cycle with carbon, or to be exported as substrate for cytosolic biosynthetic pathways or for storage in the vacuole. In this study, we show that DIC2 functions as a mitochondrial malate/citrate carrierin vivoin Arabidopsis. DIC2 knockout (dic2-1) results in growth retardation that can only be restored by expressing DIC2 but not its closest homologs DIC1 or DIC3, indicating that their substrate preferences are not identical. Malate uptake by non-energiseddic2-1mitochondria is reduced but can be restored in fully energised mitochondria by altering fumarate and pyruvate/oxaloacetate transport. A reduced citrate export but an increased citrate accumulation in substrate-fed, energiseddic2-1mitochondria suggest that DIC2 facilitates the export of citrate from the matrix. Consistent with this, metabolic defects in response to a sudden dark shift or prolonged darkness could be observed in dic2-1leaves, including altered malate, citrate and 2-oxoglutarate utilisation. There was no alteration in TCA cycle metabolite pools and NAD redox state at night; however, isotopic glucose tracing reveals a reduction in citrate labelling indic2-1which resulted in a diversion of flux towards glutamine, as well as the removal of excess malate via asparagine and threonine synthesis. Overall, these observations indicate that DIC2 is responsiblein vivofor mitochondrial malate import and citrate export which coordinate carbon metabolism between the mitochondrial matrix and the other cell compartments.SIGNIFICANCE STATEMENTMitochondria are pivotal for plant metabolism. One of their central functions is to provide carbon intermediates for the synthesis of critical building blocks, such as amino acids. Malate import and citrate export are two of the most recognised and specialised features of the mitochondrial role in the plant cellular metabolic network, yet the possibility that a single carrier would unite both functions has not been considered. Here, we have demonstrated that DIC2 preferentially fulfils these two functions inArabidopsis thaliana in vivo, making it a bifunctional gateway for two major metabolite fluxes into and out of the mitochondrial matrix in the plant cell. Our results highlight the significance of DIC2 in cooperation with other mitochondrial carriers in maintaining metabolic balance even under challenging environmental conditions.
Generation and Validation of Versatile Inducible CRISPRi Embryonic Stem Cell and Mouse Models
Authors: Li Rui , Xia Xianyou , Wang Xing , Sun Xiaoyu , Dai Zhongye , Huo Dawei , Zheng Huimin , Xiong Haiqing , He Aibin , Wu Xudong 
Published: April 2020

ABSTRACTCRISPR-Cas9 has been widely used far beyond genome editing. Fusions of deactivated Cas9 (dCas9) to transcription effectors enable interrogation of the epigenome and controlling of gene expression. However the large transgene size of dCas9-fusion hinders its applications especially in somatic tissues. Here, we develop a robust CRISPR interference (CRISPRi) system by transgenic expression of doxycycline (Dox) inducible dCas9-KRAB in mouse embryonic stem cells (iKRAB ESC). After introduction of specific gRNAs, the induced dCas9-KRAB efficiently maintains gene inactivation, though it exerts modest effects on active gene expression. Proper timing of Dox addition during cell differentiation or reprogramming allows us to study or screen spatiotemporally activated promoters or enhancers and thereby the gene functions. Furthermore, taking the ESC for blastocyst injection, we generate an iKRAB knockin (KI) mouse model that enables shut-down of gene expression and loss-of-function studiesex vivoandin vivoby a simple transduction of gRNAs. Thus, our inducible CRISPRi ESC line and KI mouse provide versatile and convenient platforms for functional interrogation and high-throughput screens of specific genes and potential regulatory elements in the setting of development or diseases.
CircularANRILisoforms switch from repressors to activators ofp15/CDKN2Bexpression during RAF1 oncogene-induced senescence
Authors: Muniz Lisa , Lazorthes Sandra , Delmas Maxime , Ouvrard Julien , Aguirrebengoa Marion , Trouche Didier , Nicolas Estelle 
Published: April 2020

AbstractLong non-coding RNAs (ncRNAs) are major regulators of gene expression and cell fate. TheINK4locus encodes the tumour suppressor proteins p15INK4b, p16INK4aand p14ARFrequired for cell cycle arrest and whose expression increases during senescence.ANRILis a ncRNA antisense to thep15gene. In proliferative cells,ANRILprevents senescence by repressingINK4genes through the recruitment of Polycomb-group proteins. In models of replicative and RASval12 oncogene-induced senescence (OIS), the expression ofANRILand Polycomb proteins decreases, thus allowingINK4derepression. Here, we found in a model of RAF1 OIS thatANRILexpression rather increases, due in particular to an increased stability. This led us to search for circularANRILisoforms, as circular RNAs are rather stable species. We found that the expression of two circularANRILincreases in several OIS models (RAF1, MEK1 and BRAF). In proliferative cells, they repressp15expression, while in RAF1 OIS, they promote full induction ofp15, p16andp14ARFexpression. Further analysis of one of these circularANRILshows that it interacts with Polycomb proteins and decreases EZH2 Polycomb protein localization and H3K27me3 at thep15andp16promoters, respectively. We propose that changes in the ratio between Polycomb proteins and circularANRILisoforms allow these isoforms to switch from repressors ofp15gene to activators of allINK4genes in RAF1 OIS. Our data reveal that regulation ofANRILexpression depends on the senescence inducer and underline the importance of circularANRILin the regulation ofINK4gene expression and senescence.
GORASPs link Golgi cisternae laterally to stabilize the rims and prevent vesiculation
Authors: Grond Rianne , Veenendaal Tineke , Duran Juan , Raote Ishier , Corstjens Sebastiaan , Delfgou Laura , El Haddouti Benaissa , Malhotra Vivek , Rabouille Catherine 
Published: April 2020

AbstractIn vitro experiments have shown GRASP65 (GORASP1) and GRASP55 (GORASP2) proteins function in stacking Golgi cisternae. However, in vivo depletion of GORASPs in metazoans have given equivocal results. We have generated a mouse lacking both GORASPs and find that Golgi cisternae remained stacked. However, the stacks are disconnected laterally from each other and the cisternal cross-sectional diameters are significantly reduced compared to their normal counterparts. These data support earlier findings on the role of GORASPs in linking stacks and we suggest that unlinking of stacks affects dynamic control of COPI budding and vesicle fusion at the rims. The net result is that cisternal cores remain stacked, but cisternal diameter is reduced by rim consumption.
Genome-wide comparisons and extrapolations of AU-rich elements in Plants withHomo sapiens
Authors: Satish Deepshikha , Panwar Anil 
Published: April 2020

AbstractThe Adenylate-Uridylate Rich elements (AREs) are adenine and uracil abundant sequences, established in ephemeral mRNAs, principally present in the 3’ untranslated region (3’ UTR). AREs are widely accepted as a cause of high turnover of the mRNAs containing them (Bakheet, 2001; Barreau, 2005; Shaw and Kamen, 1986). The mammalian ARE-mRNAs primarily translate into nuclear transcription factors, oncoproteins, cytokines, and G-protein-coupled receptors which indicates their indispensable role in the regulation of gene transcription during cell growth and differentiation, and the immune response (Chen and Shyu, 1995; Wilson et al., 1999). The present study is an attempt to comprehensively analyze the eloquent presence of AU rich elements in genome, transcriptome and 3’UTR of three important plant species (Arabidopsis thaliana, Oryza sativa and Zea mays) and compare the statistics of putative ARE motifs in plants withH.sapiens. Statistical analysis of genome-wide putative AU-rich elements revealed the explicit presence of ARE motifs in plants. This is the first study that analyses the presence of Adenylate-Uridylate Rich elements (AREs) in three different plants which can be further validated through experiments.
Placental microRNA Expression Associates with Birthweight through Control of Adipokines: Results from Two Independent Cohorts
Authors: Kennedy Elizabeth M , Hermetz Karen , Burt Amber , Everson Todd M , Deyssenroth Maya , Hao Ke , Chen Jia , Karagas Margaret R , Pei Dong , Koestler Devin C , Marsit Carmen J 
Published: April 2020

ABSTRACTMicroRNAs are non-coding RNAs that regulate gene expression post-transcriptionally. In the placenta, the master regulator of fetal growth and development, microRNAs shape the basic processes of trophoblast biology and specific microRNA have been associated with fetal growth. To comprehensively assess the role of microRNAs in placental function and fetal development, we have performed small RNA sequencing to profile placental microRNAs from two independent mother-infant cohorts: the Rhode Island Child Health Study (n=225) and the New Hampshire Birth Cohort Study (n=317). We modeled microRNA counts on infant birthweight percentile (BWP) in each cohort, while accounting for race, sex, parity and technical factors, using negative binomial generalized linear models. We identified microRNAs that were differentially expressed (DEmiRs) with BWP at false discovery rate (FDR) less than 0.05 in both cohorts. hsa-miR-532-5p (miR-532) was positively associated with BWP in both cohorts. By integrating parallel whole transcriptome and small RNA sequencing in the RICHS cohort, we identified putative targets of miR-532. These targets are enriched for pathways involved in adipogenesis, adipocytokine signaling, energy metabolism and hypoxia response, and included Leptin, which we further demonstrated to have decreasing expression with increasing BWP, particularly in male infants. Overall, we have shown a robust and reproducible association of miR-532 with BWP, which could influence BWP through regulation of adipocytokines Leptin and Adiponectin.
Cotton tipped plastic swabs for SARS-CoV2 RT-qPCR diagnosis to prevent supplies shortage
Authors: Freire-Paspuel Byron , Vega-Mariño Patricio , Velez Alberto , Castillo Paulina , Gomez-Santos Ileana Elizabeth , Cruz Marilyn , Garcia-Bereguiain Miguel Angel 
Published: April 2020

AbstractCDC and WHO guidelines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) diagnosis only recommend synthetic fiber swabs for nasopharyngeal (NP) sampling. We show that cotton tipped plastic swabs do not inhibit PCR and have equivalent performance to rayon swabs. Cotton tipped plastic swabs are massively produced worldwide and would prevent swabs supplies shortage during current high SARS-CoV2 testing demands, particularly on developing countries.
Abundance and diversity of phages, microbial taxa and antibiotic resistance genes in the sediments of the river Ganges through metagenomic approach
Authors: Kumar Narender , Gupta Amit Kumar , Sudan Sarabjeet Kour , Pal Deepika , Randhawa Vinay , Sahni Girish , Mayilraj Shanmugam , Kumar Manoj 
Published: April 2020

AbstractIn the present study, we have analyzed the metagenomic DNA from the pooled sediment sample of the river Ganges to explore the abundance and diversity of phages, microbial community and antibiotic resistance genes. Utilizing data from Illumina platform, 4174 (∼0.0013%) reads were classified for the 285 different DNA viruses largely dominated by the group of 260 distinctive phages (3602 reads, ∼86.3%). Among all, Microcystis (782 hits), Haemophilus (403), Synechococcus (386), Pseudomonas (279), Enterococcus (232), Bacillus (196), Rhodococcus (166), Caulobacter (163), Salmonella (146), Enterobacteria (143), Mycobacterium (128), Propionibacterium (71), Erwinia (70), Ralstonia (56) phages shows the highest abundance and account for approximately 90% of the total identified phages. Additionally, we have also identified corresponding host pertaining to these phages. Mainly, Proteobacteria (∼69.3%) dominates the microbial population structure. Primarily orders such as Caulobacterales (∼28%), Burkholderiales (∼13.9%), Actinomycetales (∼13.7%), Pseudomonadales (∼7.5%) signify the core section. Further, 21869 (∼0.00695%) reads were classified in 20 ARG types (classes) and 240 ARGs (subtypes) among which 4 ARG types namely multidrug resistance (MDR) (12041 reads, ∼55%), bacitracin (3202 reads, ∼15%), macrolide-lincosamide-streptogramin (MLS) (1744 reads, ∼7.98%), and fosmidomycin (990 reads, ∼4.53%) has the highest abundance. Simultaneously, six resistance mechanisms were also recognized with the dominance of antibiotic efflux (72.8%, 15919 reads). The results unveil the distribution of (pro)-phages; microbial community and various ARGs in the Ganges river sediments. Further research on these identified phage(s) could be used in phage-based therapeutics against pathogenic bacteria.
Crystal structure of gluconate 5-dehydrogenase from Lentibacter algarum
Authors: Tian Dengke , Fu Xueqi , Cao Wenqiang , Yuan Hong 
Published: April 2020

Gluconate 5-dehydrogenase (Ga5DH; EC 1.1.1.69) from Lentibacter algarum (LaGa5DH) was recombinantly expressed in Escherichia coli and purified to homogeneity. The protein was crystallized and the crystal structure was solved at 2.1 Å resolution. The crystal belonged to the monoclinic system, with space group P1 and unit-cell parameters a = 55.42, b = 55.48, c = 79.16 Å, α = 100.51, β = 105.66, γ = 97.99°. The structure revealed LaGaDH to be a tetramer, with each subunit consisting of six α-helices and three antiparallel β-hairpins. LaGa5DH has high structural similarity to other Ga5DH proteins, demonstrating that this enzyme is highly conserved.
Added cultural distance and ownership in cross-border acquisitions
Authors: Kim Hyun Gon , Gaur Ajai S. , Mukherjee Debmalya 
Published: April 2020

PurposeAs multinational companies enter different countries, the extent of cultural unfamiliarity they face depends on their most recent entry. We examine this pattern of added cultural distance between a newly entered target country and the closest previous one and its effect on ownership decisions in each cross-border acquisition (CBA). We also examine the combined effect of added cultural distance and time between successive acquisitions on such decisions.Design/methodology/approachThe sample came from the Thomson Financial Securities Data Corporation (SDC) Platinum database, which spans different source and target countries for a 25-year period (1980–2014). We collected firm- (acquirer and target), industry-, country-, and transaction-level variables from SDC. After merging information from the different sources, the final sample comprised 10,423 CBA observations from 138 target countries.FindingsOur findings reveal that the ownership share decision is affected negatively by added cultural distance but positively by the time between two successive acquisitions. In addition, prior ownership and geographic distance moderate the relationship between added cultural distance and ownership in CBAs.Practical implicationsOur findings suggest that MNCs' managers who consider CBAs need to carefully examine closest previous target information and CBA experience, rather than focusing on direct cultural distance between the focal firm and target firm. Additionally, they should also consider the relevance of key contingency factors.Originality/valueWe disentangle the effects of added cultural distance on CBA ownership decisions and explore the boundary conditions of this relationship.
The social management of human capital: basic principles and methodological approaches
Authors: Popkova Elena 
Published: April 2020

PurposeThe purpose of the paper is to model the modern global practice of social management of human capital – at the state and corporate levels – to determine the perspectives of its optimization and to develop the basic principles of a new methodological approach to social management of human capital, which is preferable in the conditions of social market economy.Design/methodology/approachThe author uses mathematical tools, including correlation and regression analysis. These are applied to determine the influence of each of the 12 indicators for the labor market that are presented as part of The World Economic Forum's (WEF’s) ”The Global Competitiveness Report 2019” on The United Nations Development Programme's (UNDP) Human Development Index. The research objects are countries from each of the four categories of nations, as distinguished by UNDP, in the Human Development Index. By unifying the 2019 data from UNDP and WEF, a data set is formed.FindingsIt is substantiated that in modern economic practice, it is impossible to achieve the “ideal” conditions necessary for applying existing methodological approaches to the social management of human capital, which reduces how effectively current approaches function. Foundation on the existing methods leads to uncertainty as to management of human capital, which is social by 95.14% in 2019. Though the achieved value of the social management of human capital is close to being optimal, it is still not enough to achieve a high level of human development, which was 0.685 on average for the global economy in 2019 and is likely to increase by 31.43% until 2025, for acknowledging the social market status of the modern economy.Originality/valueIt is proven that there is a need for a new, mixed, methodological approach to the social management of human capital, which would optimally combine the best practices of both state and corporate management. The principles for the practical implementation of such an approach are offered, and proposals are developed to substantiate the contribution of this approach to the achievement of the global goals of sustainable development.
Financial integration and macroeconomic volatility in Zimbabwe
Authors: Makoto Richard 
Published: April 2020

PurposeMany developing countries are pursuing policies that foster international financial integration after decades of financial repression. Greater access to foreign financial markets may have both positive and negative impact on the performance of the economy. One of the concerns of international financial integration is macroeconomic volatility which may affect both monetary and real sectors. Zimbabwe has chosen to pursue a financial liberalization strategy in the form of imperfect financial integration following periods of excessive domestic shocks. An upsurge of capital flows since the epic of economic crisis in the 2000s has been observed with varying macroeconomic impacts. This study empirically examines the impact of partial international financial integration on the volatility of macroeconomic variables.Design/methodology/approachThe study utilized an ARDL Model suggested by Pesaran et al., (2003) which is appropriate for short time periods.FindingsThe results show that financial integration has a negative effect on output volatility while insignificant on consumption volatility.Practical implicationsThe study recommends that the country should gradually liberalize the capital account and properly sequence financial development reforms in order to minimize losses from global financial integration.Originality/valueThe study used time series for Zimbabwe during a period of external imbalance, repeated economic cycles, sudden stops in capital flows and limited scope of imperfect financial integration. Findings in such an economy will be a referral for policymakers in other economies that would want to pursue international financial integration.
A meta-analysis: capital structure and firm performance
Authors: Dao Binh Thi Thanh , Ta Tram Dieu Ngoc 
Published: April 2020

PurposeThe paper aims at providing insights on the relationship between capital structure and performance of the firm by employing meta-analytical approach to obtain a synthesized result out of controversial studies as well as the sources for such inconsistency.Design/methodology/approachUsing secondary data, the analysis is divided into two main parts with concerns to the overall strength of the relationship, the effect size and the potential paper-specific characteristics influencing the magnitude of impacts between leverage and firm performance (moderators of the relationship). Overall, a total number of 32 journals, reviews and school presses were selected besides online libraries and publishing platforms. There were 50 papers with 340 studies chosen from 2004 to 2019, of which data range from 1998 to 2017.FindingsUsing Hedges et al. (1985,1988), descriptive and quantitative analysis have been conducted to confirm that corporate performance is negatively related to capital decisions, which inclines toward trade-off model with agency costs and pecking order theory. The estimation induces rather small effect size that implies sufficiently large sample size to be effectively investigated. In terms of moderator analysis, random-effects meta-regression models of three different techniques are used to increase the robustness in research findings, showing statistically significant elements as publication status, factor of industry and proxy of firm performance.Originality/valueThis paper is one of the first papers presenting meta-analysis in capital structure and performance for two languages, Vietnamese and English, providing a consistent result with previous worldwide papers.