bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of near infrared spectroscopy for sporozoite detection in mosquitoes infected with wild-strain parasites from asymptomatic gametocyte carriers in Kilifi Kenya
Authors: Maia Marta F. , Wagah Martin G. , Karisa Jonathan , Mwakesi Robert , Mure Festus , Muturi Martha , Wambua Juliana , Hamaluba Mainga , Dowell Floyd E. , Bejon Philip , Kapulu Melissa C. 
Published: July 2020

ABSTRACTBackgroundScreening forPlasmodiumspp. sporozoite infection in mosquitoes is routinely done using ELISA (enzyme-linked immunosorbent assay). Near infrared spectroscopy (NIRS), a fast and non-destructive method, has recently been shown to distinguish, with 95% accuracy, between uninfected and sporozoite-infected mosquitoes using laboratory strains ofPlasmodium falciparum(PfN54). The aim of this present study was to further investigate the reproducibility of NIRS to identify sporozoite infection in mosquitoes infected using field isolates ofP. falciparumgametocytes from asymptomatic carriers.MethodsHealthy individuals (aged 5 years and above) were screened for gametocytaemia by thick-smear microscopy in an area of moderate transmission along the Coast of Kenya between May and September 2018. Asymptomatic gametocyte carriers were recruited for mosquito feeding assays, direct membrane feeding (DMFA) and direct skin feeding (DFA), using insectary-rearedAnopheles gambiaes.s (Kilifi strain). Mosquitoes were kept for 14-days post feeding after which they were scanned using NIRS and subsequently analysed for sporozoite infection using circumsporozoite-ELISA. Predictive models were explored using partial least square regressions (PLS).ResultsTwo hundred and ninety-nine (299) individuals were screened for malaria parasites, 74 (24.8%) were found with circulating asexual parasites, and 16 (5.4%) withP. falciparumgametocyte stages. Fourteen (14) asymptomatic gametocyte carriers were recruited to the study for mosquito feeding assays. A total of 134 (7%, 134/1881) sporozoite-infected mosquitoes were obtained from 9 successful experiments. Three different training datasets composed of infected and uninfected mosquitoes were analysed. The PLS models were unable to distinguish between sporozoite-infected and uninfected mosquitoes. A predictive model could not be generated.ConclusionsThe results of this study were not consistent with previous published research on NIRS for detection of sporozoite infection in the same mosquito species and may reflect differences between laboratory and field conditions. The current findings indicate that methods for sporozoite detection should be tested on field isolates at an early stage in their development and are informative for future research seeking novel high-throughput methods for parasite detection in mosquitoes.
Expression ofWnt5adefines the major progenitors of fetal and adult Leydig cells
Authors: Ademi Herta , Stévant Isabelle , Rands Chris M , Conne Béatrice , Nef Serge 
Published: July 2020

SummaryLeydig cells (LCs) are the major androgen-producing cells in the testes. They arise from steroidogenic progenitors, whose origins, maintenance and differentiation dynamics remain largely unknown. Here, we identifiedWnt5aas a specific marker of steroidogenic progenitors, whose expression begins at around E11.5-E12.5 in interstitial cells of the fetal mouse testis.In vivolineage tracing indicates thatWnt5a-expressing progenitors are initially present in large numbers in the fetal testis and then progressively decrease as development progresses. We provide evidence thatWnt5a-expressing cells arebona fideprogenitors of peritubular myoid cells as well as fetal and adult LCs, contributing to most of the LCs present in the fetal and adult testis. Additionally, we show in the adult testis thatWnt5aexpression is restricted to a subset of LCs exhibiting a slow but noticeable clonal expansion, revealing hitherto unappreciated proliferation of fully differentiated LCs as a contribution to the adult LC pool.
A>G substitutions on a heavy chain of mitochondrial genome marks an increased level of aerobic metabolism in warm versus cold vertebrates
Authors: Mikhailova Alina G. , Iliushchenko Dmitrii , Shamansky Victor , Mikhailova Alina A. , Ushakova Kristina , Tretyakov Evgenii , Oreshkov Sergey , Knorre Dmitry , Polishchuk Leonard , Lawless Dylan , Kuzmin Aleksandr , Denisov Stepan , Kozenkov Ivan , Mazunin Ilya , Kunz Wolfram , Tanaka Masashi , Makeev Vsevolod , Castilho Rita , Yurov Valerian , Kuptsov Alexander , Fellay Jacques , Khrapko Konstantin , Gunbin Konstantin , Popadin Konstantin 
Published: July 2020

ABSTRACTThe variation in the mutational spectrum of the mitochondrial genome (mtDNA) among species is not well understood. Recently, we demonstrated an increase in A>G substitutions on a heavy chain (hereafter AH>GH) of mtDNA in aged mammals, interpreting it as a hallmark of age-related oxidative damage. In this study, we hypothesized that the occurrence of AH>GHsubstitutions may depend on the level of aerobic metabolism, which can be inferred from an organism’s body temperature. To test this hypothesis, we used body temperature in endotherms and environmental temperature in ectotherms as proxies for metabolic rate and reconstructed mtDNA mutational spectra for 1350 vertebrate species. Our results showed that temperature was associated with increased rates of AH>GHand asymmetry of AH>GHin different species of ray-finned fishes and within geographically distinct clades of European anchovy. Analysis of nucleotide composition in the most neutral synonymous sites of fishes revealed that warm-water species were expectedly more A-poor and G-rich compared to cold-water species. Finally, we extended our analyses to all vertebrates and observed higher AH>GHand increased asymmetry of AH>GHin warm-blooded (mammals and birds) compared to cold-blooded (Actinopterygii, amphibia, reptilia) vertebrate classes. Overall, our findings suggest that temperature, through its influence on metabolism and oxidative damage, shapes the mutational properties and nucleotide content of the mtDNA in all vertebrates.
Pharmacological prevention of neonatal opioid withdrawal in a pregnant guinea pig model
Authors: Safa Alireza , Lau Allison R. , Aten Sydney , Schilling Karl , Bales Karen L. , Miller Victoria A. , Fitzgerald Julie , Chen Min , Hill Kasey , Dzwigalski Kyle , Obrietan Karl , Phelps Mitch A. , Sadee Wolfgang , Oberdick John 
Published: July 2020

ABSTRACTNewborns exposed to prenatal opioids often experience intense postnatal withdrawal after cessation of the opioid, called neonatal opioid withdrawal syndrome (NOWS), with limited pre- and postnatal therapeutic options available. In a prior study in pregnant mice we demonstrated that the peripherally selective neutral opioid antagonist, 6β-naltrexol (6BN), is a promising drug candidate for preventive prenatal treatment of NOWS. Here, we have developed methadone (MTD) treated pregnant guinea pigs as a physiologically more suitable model, enabling detection of robust spontaneous neonatal withdrawal. Prenatal MTD significantly aggravates two classic maternal separation stress behaviors in newborn guinea pigs: calling (vocalizing) and searching (locomotion) - natural attachment behaviors thought to be controlled by the endogenous opioid system. In addition, prenatal MTD significantly increases the levels of plasma cortisol in newborns, showing that cessation of MTD at birth engages the hypothalamic-pituitary-adrenal (HPA) axis. We find that co-administration of 6BN with MTD prevents these withdrawal symptoms in newborn pups with extreme potency (ID50 ∼0.02 mg/kg), at doses unlikely to induce maternal or fetal withdrawal or to interfere with opioid antinociception based on many prior studies. Furthermore, we demonstrate a similarly high potency of 6BN in preventing opioid withdrawal in adult guinea pigs (ID50 = 0.01 mg/kg). This suggests a novel receptor mechanism to account for the selectively high potency of 6BN to suppress opioid dependence as compared to its low potency as a classical opioid antagonist. In conclusion, 6BN is an attractive compound for development of a preventive therapy for NOWS.
Characterization of Induced Susceptibility Effects of Soybean Aphid on Soybean
Authors: Neupane Surendra , Varenhorst Adam J. , Nepal Madhav P. 
Published: July 2020

ABSTRACTSoybean aphid (SBA) is one of the major pests of soybean (Glycine max) in the United States of America. The main objective of this research was to characterize interactions between two different biotypes of soybean aphids in susceptible and resistant soybean cultivars. Demographic and transcriptomic responses of susceptible and resistant (Rag1) soybean cultivars to aphid feeding were investigated in soybean plants colonized by aphids (biotype 1) in the presence or absence of inducer population (biotype 2) at day 1 and day 11. Leaves tissues collected at day 1 and day 11 post infestation were used for RNA sequencing, and ten RNA datasets with 266,535,654 sequence reads were analyzed. In the presence of inducer population, we found 746 and 243 differentially expressed genes (DEGs) in susceptible and resistant cultivars, respectively at day 1, whereas 981 and 377 DEGs were found in susceptible and resistant cultivars, respectively at day 11. Enrichment analysis showed a response to chitin, lignin catabolic and metabolic process, asparagine metabolic process, response to chemical unique to treatment with no inducer population, whereas, response to reactive oxygen species, photosynthesis, regulation of endopeptidase activity unique to treatment with inducer population. Furthermore, 14 DEGs were observed inRagQTLs regions, particularly six DEGs inRag1containing QTL. The identified DEGs in the experiment in both resistant and susceptible cultivars during the interaction of soybean and SBA are potential candidates for furthering investigation into induced susceptibility.
Integration of phenomics and transcriptomics data to reveal drivers of inflammatory processes in the skin
Authors: Batra Richa , Garzorz-Stark Natalie , Lauffer Felix , Jargosch Manja , Pilz Caroline , Roenneberg Sophie , Schäbitz Alexander , Böhner Alexander , Seiringer Peter , Thomas Jenny , Fereydouni Bentolhoda , Kutkaite Ginte , Menden Michael , Tsoi Lam C , Gudjonsson Johann E , Theis F Fabian , Biedermann Tilo , Schmidt-Weber Carsten B , Müller Nikola , Eyerich Stefanie , Eyerich Kilian 
Published: July 2020

AbstractChronic inflammatory diseases are characterized by complex interactions between genetic predisposition and tissue-specific immune responses. This heterogeneity complicates diagnoses and the ability to exploit omics approaches to improve disease management, develop more effective therapeutics, and apply precision medicine. Using skin inflammation as a model, we developed a method that integrates deep clinical phenotyping information (phenomics) with transcriptome data of lesional and non-lesional skin (564 samples) to identify clinically-relevant gene signatures. It led us to discover so-far unexplored factors, including CCAAT Enhancer-Binding Protein Beta (CEBPB) in neutrophil invasion, and Pituitary Tumor-Transforming 2 (PTTG2) in the pathogenic epithelial response to inflammation. These factors were validated using genetically-modified human skin equivalents, migration assays, andin situimaging. Thus, by meaningful integration of deep clinical phenotyping and omics data we reveal hidden drivers of clinically-relevant biological processes.
Laminin N-terminus α31 expression during development is lethal and causes widespread tissue-specific defects in a transgenic mouse model
Authors: Sugden Conor J. , Iorio Valentina , Troughton Lee D. , Liu Ke , Bou-Gharios George , Hamill Kevin J. 
Published: July 2020

AbstractLaminins are essential components of all basement membranes where they regulate an extensive array of tissue functions. Alternative splicing from the laminin α3 gene produces a non-laminin but netrin-like protein, Laminin N terminus α31 (LaNt α31). LaNt α31 is widely expressed in intact tissue and is upregulated in epithelial cancers and during wound healing. In vitro functional studies have shown that LaNt α31 can influence numerous aspects of epithelial cell behaviourviamodifying matrix organisation, suggesting a new model of laminin auto-regulation. However, the function of this protein has not been established beyond the epithelium and it has never been studied in vivo. Here, a mouse transgenic line was generated using the ubiquitin C promoter to drive inducible expression of LaNt α31. When expression was induced at embryonic day 15.5, LaNt α31 transgenic animals were not viable at birth, exhibiting localised regions of erythema. Numerous striking defects were apparent histologically, including extra-vascular erythrocytes in multiple tissues, kidney epithelial detachment, tubular dilation, interstitial bleeding, and thickening of tubule basement membranes, disruption of the epidermal basal cell layer and of the hair follicle outer root sheath, and ~50% reduction of cell numbers in the liver associated with depletion of hematopoietic erythrocytic foci. These findings demonstrate that LaNt α31 can influence tissue morphogenesis during development. More broadly, these data provide the first in vivo evidence to support an emerging model of laminin self-regulation and provide a valuable model for onward investigation into this important area.Summary StatementExpression during development of Laminin N-terminus α31, a netrin-like laminin splice isoform, caused defects indicating basement membrane disruption in multiple tissues; providing the first in vivo evidence for laminin self-regulation.
Sex-specific responses to cold in a very cold-tolerant, northernDrosophila species
Authors: Parker Darren J. , Envall Tapio , Ritchie Michael G. , Kankare Maaria 
Published: July 2020

AbstractOrganisms can plastically alter resource allocation in response to changing environmental factors. For example, in harsh conditions organisms are expected to shift investment from reproduction towards survival, however, the factors and mechanisms that govern the magnitude of such shifts are relatively poorly studied. Here we compared the impact of cold on males and females of the highly cold-tolerant speciesDrosophila montanaat the phenotypic and transcriptomic levels. Although both sexes showed similar changes in cold tolerance and gene expression in response to cold treatment, indicating that the majority of changes are concordant between the sexes, we identified a clear reduction in sexually dimorphic gene expression, suggesting that preparing for colder season also involves reducing investment in sex-specific traits. This reduction was larger in males than females, as expected if male sexual traits are more condition-dependent than female traits, as predicted by theory. Gene expression changes were primarily associated with shifts in metabolic profile which likely play a role in increasing cold tolerance. Finally, we found that the expression of immune genes was reduced following cold treatment, suggesting that reduced investment in immunity may be important in helping flies survive colder periods.
Differences in developmental potential predict the contrasting patterns of dental diversification in characiform and cypriniform fishes
Authors: Jandzik David , Stock David W 
Published: July 2020

AbstractMorphological diversification during adaptive radiation may depend on factors external or internal to the lineage. We provide evidence for the latter in characiform fishes (tetras and piranhas), which exhibit extensive dental diversity. Phylogenetic character mapping supported regain of lost teeth as contributing to this diversity. To test for latent potential for dentition that would facilitate its evolutionary expansion, we overexpressed a tooth initiation signal, the tumor necrosis factor pathway ligand ectodysplasin, in a model characiform, the Mexican Tetra (Astyanax mexicanus). This manipulation resulted in extensive ectopic dentition, in contrast to its previously-reported limited effect in the Zebrafish (Danio rerio). Tooth location in the Order Cypriniformes, to which the Zebrafish belongs, is much more restricted than in characiforms, a pattern that may be explained by differences in the retention of ancestral developmental potential. Our results suggest that differences in evolvability between lineages may lead to contrasting patterns of diversification.
Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response
Authors: McMahon Kerrie-Ann , Stroud David A. , Gambin Yann , Tillu Vikas A. , Bastiani Michele , Sierecki Emma , Polinkovsky Mark , Hall Thomas E. , Gomez Guillermo A. , Wu Yeping , Parat Marie-Odile , Martel Nick , Lo Harriet P. , Khanna Kum Kum , Alexandrov Kirill , Daly Roger , Yap Alpha S. , Ryan Michael T. , Parton Robert G. 
Published: July 2020

AbstractCaveolae-associated protein 3 (cavin3), a putative tumor suppressor protein, is inactivated in most cancers. We characterized how cavin3 affects the cellular proteome using genome-edited cells together with label-free quantitative proteomics. These studies revealed a prominent role for cavin3 in DNA repair with BRCA1 and BRCA1 A-complex components being downregulated on cavin3 deletion. Cellular and cell-free expression assays, we show a direct interaction between BRCA1 and cavin3. Association of BRCA1 and cavin3 occurs when cavin3 is released from caveolae that are disassembled in response to UV and mechanical stress. Supporting a role in DNA repair, cavin3-deficient cells were sensitized to the effects of PARP inhibition, which compromises DNA repair, and showed reduced recruitment of the BRCA1 A-complex to UV DNA damage foci. Overexpression and RNAi-depletion revealed that cavin3 sensitized various cancer cells to UV-induced apoptosis. We conclude that cavin3 functions together with BRCA1 in multiple pathways that contribute to tumorigenesis.
Dynamic control over feedback regulatory mechanisms improves NADPH fluxes and xylitol biosynthesis in engineeredE. coli
Authors: Li Shuai , Moreb Eirik A. , Ye Zhixia , Hennigan Jennifer N. , Castellanos Daniel Baez , Yang Tian , Lynch Michael D. 
Published: July 2020

AbstractWe report improved NADPH flux and xylitol biosynthesis in engineeredE. coli. Xylitol is produced from xylose via an NADPH dependent reductase. We utilize two-stage dynamic metabolic control to compare two approaches to optimize xylitol biosynthesis, a stoichiometric approach, wherein competitive fluxes are decreased, and a regulatory approach wherein the levels of key regulatory metabolites are reduced. The stoichiometric and regulatory approaches lead to a 16 fold and 100 fold improvement in xylitol production, respectively. Strains with reduced levels of enoyl-ACP reductase and glucose-6-phosphate dehydrogenase, led to altered metabolite pools resulting in the activation of the membrane bound transhydrogenase and a new NADPH generation pathway, namely pyruvate ferredoxin oxidoreductase coupled with NADPH dependent ferredoxin reductase, leading to increased NADPH fluxes, despite a reduction in NADPH pools. These strains produced titers of 200 g/L of xylitol from xylose at 86% of theoretical yield in instrumented bioreactors. We expect dynamic control over enoyl-ACP reductase and glucose-6-phosphate dehydrogenase to broadly enable improved NADPH dependent bioconversions.HighlightsDecreases in NADPH pools lead to increased NADPH fluxesPyruvate ferredoxin oxidoreductase coupled with NADPH-ferredoxin reductase improves NADPH productionin vivo.Dynamic reduction in acyl-ACP/CoA pools alleviate inhibition of membrane bound transhydrogenase and improve NADPH fluxXylitol titers > 200g/L in fed batch fermentations with xylose as a sole feedstock.
Innovation process in the business ecosystem: the four cooperations practices in the media platform
Authors: Lee Yeon W. , Moon Hwy-Chang , Yin Wenyan 
Published: July 2020

PurposeThe main purpose of this research is to construct a generalized set of innovation processes that occur at the ecosystem level based on the academic research. The study analyzes the cultural and creativity-driven over-the-top (OTT) platform that encompasses diverse network of ecosystem members by utilizing the four cooperation practices.Design/methodology/approachThis study begins with the literature review that discusses various topics related to ecosystem (e.g. service innovation, innovative ecosystem). Then, this study introduces a new conceptual framework that describes how cooperations occur in the ecosystem. Finally, a qualitative and explorative case study of the OTT platforms in the global context is conducted.FindingsThe application of the framework reveals how co-innovative business ecosystems demonstrate co-evolution through different structures and directions. An ecosystem can evolve by incorporating other industries (i.e. horizontal growth or broadening strategy) to deepen and broaden the industry integration.Originality/valueAs an explorative approach that opens the discussion on how co-innovation and co-evolution occur at the ecosystem level, particularly in the culture and creativity-driven industry, the value of this research extends to other similar industries where diverse actors such as technology firms, Internet firms, direct consumers, government and even the society impact the type of product and service and shape the evolution of the entire ecosystem.
Do FDI inflows affect the off-balance sheet activities of banks in GCC economies?
Authors: Saif-Alyousfi Abdulazeez Y.H. 
Published: July 2020

PurposeThis paper investigates and compares the impact of foreign direct investment (FDI) inflows (flow and stock) on bank off-balance sheet (OBS) activities in aggregate as well as at the level of conventional and Islamic banks in GCC countries. It also tests hypotheses of direct and indirect impacts of FDI flow and FDI stock on OBS activities.Design/methodology/approachThis paper uses both static and dynamic panel generalized methods of moments (GMM) estimation techniques to analyze the data of 70 GCC banks (45 conventional and 25 Islamic banks) over the period 1995–2017.FindingsEmpirical results indicate that FDI flow and FDI stock have a significant negative direct impact on OBS activities of GCC banks. The results lend support for the direct channel hypothesis for the effect of FDI on OBS activities and find no evidence in support of the indirect channel hypothesis. OBS activities from conventional banks appear to be more affected than those from Islamic banks.Practical implicationsThe results of this study are expected to trigger appropriate policy response from the central banks of the respective GCC countries as well as their governments.Originality/valueIt is widely recognized that FDI inflows are of great importance to the economic development of emerging and developing countries. However, their impact on bank OBS activities has so far not been subject to accurate empirical assessment. This paper aims to fill this gap by providing an in-depth quantitative analysis of the impact of FDI flow and FDI stock separately, on bank OBS activities for both conventional and Islamic banks in GCC countries. It distinguishes between direct and indirect channels through which FDI flow and FDI stock may affect OBS activities for banks as a whole and both conventional and Islamic banks separately. It also uses both static and dynamic panel GMM estimation techniques to analyze the data.