bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of a Ketogenic Diet and Synergy with Rapamycin in a Mouse Model of Breast Cancer
Authors: Zou Yiyu , Fineberg Susan , Pearlman Alexander , Feinman Richard D. , Fine Eugene J. 
Published: May 2020

AbstractBackgroundThe effects of diet in cancer, in general, and breast cancer in particular, are not well understood. Insulin inhibition in ketogenic, high fat diets, modulate downstream signaling molecules and are postulated to have therapeutic benefits. Obesity and diabetes have been associated with higher incidence of breast cancer. Addition of anti-cancer drugs together with diet is also not well studied.MethodsTwo diets, one ketogenic, the other standard mouse chow, were tested in a spontaneous breast cancer model in mice. The diets were implemented either with or without added rapamycin, an mTOR inhibitor and potential anti-cancer drug.ResultsBlood glucose and insulin concentrations in mice ingesting the ketogenic diet (KD) were significantly lower, whereas beta hydroxybutyrate (BHB) levels were significantly higher, respectively, than in mice on the standard diet (SD). Growth of primary breast tumors and lung metastases were inhibited, and lifespans were longer in the KD mice compared to mice on the SD (p<0.005). Rapamycin improved survival in both mouse diet groups, but when combined with the KD was more effective than when combined with the SD.ConclusionsThe study provides proof of principle that a ketogenic diet a) results in serum insulin reduction and ketosis in a spontaneous breast cancer mouse model; b) can serve as a therapeutic anti-cancer agent; and c) can enhance the effects of rapamycin, an anti-cancer drug, permitting dose reduction for comparable effect. Further, the ketogenic diet in this model produces superior cancer control than standard mouse chow whether with or without added rapamycin.
Genome-wide identification ofAedes albopictuslong noncoding RNAs and their association with dengue and zika virus infection
Authors: Azlan Azali , Obeidat Sattam M. , Das Kumitaa Theva , Yunus Muhammad Amir , Azzam Ghows 
Published: May 2020

AbstractThe Asian tiger mosquito,Aedes albopictus(Ae. albopictus), is an important vector that transmits arboviruses such as dengue (DENV), Zika (ZIKV) and Chikungunya virus (CHIKV). On the other hand, long noncoding RNAs (lncRNAs) are known to regulate various biological processes. Knowledge onAe. albopictuslncRNAs and their functional role in virus-host interactions are still limited. Here, we identified and characterized the lncRNAs in the genome of an arbovirus vector,Ae. albopictus, and evaluated their potential involvement in DENV and ZIKV infection. We used 148 public datasets, and identified a total of 10, 867 novel lncRNA transcripts, of which 5,809, 4,139, and 919 were intergenic, intronic and antisense respectively. TheAe. albopictuslncRNAs shared many characteristics with other species such as short length, low GC content, and low sequence conservation. RNA-sequencing ofAe. albopictuscells infected with DENV and ZIKV showed that the expression of lncRNAs was altered upon virus infection. Target prediction analysis revealed thatAe. albopictuslncRNAs may regulate the expression of genes involved in immunity and other metabolic and cellular processes. To verify the role of lncRNAs in virus infection, we generated mutation in lncRNA loci using CRISPR-Cas9, and discovered that two lncRNA loci mutations, namely XLOC_029733 (novel lncRNA transcript id: lncRNA_27639.2) and LOC115270134 (known lncRNA transcript id: XR_003899061.1) resulted in enhancement of DENV and ZIKV replication. The results presented here provide an important foundation for future studies of lncRNAs and their relationship with virus infection inAe. albopictus.Author summaryAe. albopictusis an important vector of arboviruses such as dengue and Zika. Studies on virus-host interaction at gene expression and molecular level are crucial especially in devising methods to inhibit virus replication inAedesmosquito. Previous reports showed that, besides protein-coding genes, noncoding RNAs such as lncRNAs are also involved in virus-host interaction. In this study, we report a comprehensive catalog of novel lncRNA transcripts in the genome ofAe. albopictus. We also show that the expression of lncRNAs was altered upon infection with dengue and Zika. Additionally, depletion of certain lncRNAs resulted in increased replication of dengue and Zika; hence, suggesting potential association of lncRNAs in virus infection. Results of this study provide a new avenue to the investigation of mosquito-virus interactions that may potentially pave way to the development of novel methods in vector control.
Comparison of the knockdown resistance locus (kdr) inAnopheles stephensi,An. arabiensis, andCulex pipiens s.l.suggests differing mechanisms of pyrethroid resistance in east Ethiopia
Authors: Carter Tamar E. , Gebresilassie Araya , Hansel Shantoy , Damodaran Lambodhar , Montgomery Callum , Bonnell Victoria , Lopez Karen , Janies Daniel , Yared Solomon 
Published: May 2020

AbstractThe malaria vector,Anopheles stephensi, which is typically restricted to South Asia and the Middle East, was recently detected in the Horn of Africa. Controlling the spread of this vector could involve integrated vector control that considers the status of insecticide resistance of multiple vector species in the region. Previous reports indicate that the knockdown resistance mutations (kdr) in the voltage-gated sodium channel (vgsc) are absent in both pyrethroid resistant and sensitive variants ofAn. stephensiin east Ethiopia but similar information on other vector species in the same areas is limited. In this study,kdrand the neighboring intron was analyzed inAn. stephensi,An. arabiensis, andCulex pipiens s. l. collected in east Ethiopia between 2016 and 2017. Sequence analysis revealed that all ofCx. pipiens s.l.(n = 42) and 71.6% of theAn. arabiensis(n=67) carriedkdrL1014F known to confer target-site pyrethroid resistance. Intronic variation was only observed inAn. stephensi(segregating sites = 6, haplotypes = 3) previously shown to have no kdr mutations. In addition, no evidence of non-neutral evolutionary processes was detected at theAn. stephensi kdrintron which further supports target-site mechanism not being a major resistance mechanism in thisAn. stephensipopulation. Overall, these results suggest differences in evolved mechanisms of pyrethroid/DDT resistance in populations of vector species from the same region. Variation in insecticide resistance mechanisms in East Ethiopian mosquito vectors highlight possible species or population specific biological factors and distinct environmental exposures that shape their evolution.
SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models
Authors: Wang Yupeng , Jaime-Lara Rosario B. , Roy Abhrarup , Sun Ying , Liu Xinyue , Joseph Paule V. 
Published: May 2020

AbstractWe propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of “strong enhancer” chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. For any DNA sequence, sequentialk-mer (k=5, 7, 9 and 11) fold changes relative to randomly selected non-coding sequences were used as features for deep learning models. Three deep learning models were implemented, including multi-layer perceptron (MLP), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). All models in SeqEnhDL outperform state-of-the-art enhancer classifiers including gkm-SVM and DanQ, with regard to distinguishing cell type-specific enhancers from randomly selected non-coding sequences. Moreover, SeqEnhDL is able to directly discriminate enhancers from different cell types, which has not been achieved by other enhancer classifiers. Our analysis suggests that both enhancers and their tissue-specificity can be accurately identified according to their sequence features. SeqEnhDL is publicly available athttps://github.com/wyp1125/SeqEnhDL.
Biochemical and Molecular Characterization, and Bioprospecting of Drought Tolerant Actinomycetes from Maize Rhizosphere Soil
Authors: Chukwuneme Chinenyenwa Fortune , Babalola Olubukola Oluranti , Kutu Funso Raphael , Ojuederie Omena Bernard 
Published: May 2020

AbstractDrought is a major limitation to maize cultivation around the globe. Seven actinomycetes strains were isolated from maize rhizosphere soils in Mahikeng, North-West Province, South Africa. The isolates were biochemically characterized and identified with 16S rRNA gene sequence analysis. Isolates were also screenedin vitrofor abiotic stress tolerance to different concentrations of NaCl, pH, and polyethylene glycol (PEG 8000), as well as for biosynthesis of drought tolerance genes namely Glutathione peroxidase (GPX), Glycine-rich RNA binding protein (GRP), Desiccation protectant protein (DSP), Guanosine triphosphate binding protein (GTP) and plant growth-promoting genes:1-aminocyclopropane-1-carboxylate deaminase (accd) and siderophore biosynthesis (Sid). About 71.43% of isolates were of the genusStreptomyces(99-100% similarity), while 14.29% belong to the genusArthrobacter(R15) and 14.29% to the genusMicrobacterium(S11) respectively (99% similarity). Five isolates had their optimum growth at 35°C.Arthrobacter arilaitensis(R15) grew and tolerated 5%, 10%, and 20% PEG at 120 h. Root length increased by 110.53% in PEG treated maize seeds (−0.30 MPa) inoculated withStreptomyces pseudovenezuelae (S20) compared to the un-inoculated control. Likewise, germination percentage and vigor index increased by 37.53% and 194.81% respectively in PEG treated seeds inoculated with S20 than the un-inoculated PEG treated seeds. ACC deaminase gene was amplified in all the isolates, while the gene for siderophore biosynthesis was amplified in 85.71% of the isolates. Genes for the synthesis of GPX, GRP, DSP and GTP were amplified inArthrobacter arilaitensis(R15) andStreptomyces pseudovenezuelae(S20) which lacked GTP. The amplification of drought-tolerant and plant growth-promoting primers indicates the possible presence of these genes in the isolates. These isolates have the potential for use as bio-inoculants, not only to improve drought tolerance in maize but also to be utilized as biofertilizers and biocontrol agents to facilitate growth promotion.
The anticipated potential nuclear localization sequence of ‘CandidatusPhytoplasma mali’ SAP11-like protein is required for TCP binding but not for transport into the nucleus
Authors: Strohmayer Alisa , Schwarz Timothy , Braun Mario , Krczal Gabi , Boonrod Kajohn 
Published: May 2020

AbstractThe plant pathogen ‘CandidatusPhytoplasma mali’ (‘Ca. P. mali’) is the causing agent of apple proliferation that leads to heavy damage in apple production all over Europe. To identify and analyze effector proteins of plant pathogens is an important strategy in plant disease research. Here, we report that the SAP11-like protein of‘Ca. P. mali’ induces crinkled leaves and siliques and witches’ broom symptoms in transgenicArabidopsis thaliana(A. thaliana) plants and binds to 6 members of class I and all members of class II TCP (TEOSINE BRANCHES/ CYCLOIDEA/PROLIFERATING CELL FACTOR) transcription factors ofA. thalianain yeast two-hybrid assays. Moreover, we demonstrate that the protein localizes actively into the plant nucleus without requiring the nuclear leader sequence (NLS). We also identified a 17 amino acid stretch previously predicted to be a nuclear leader sequence that is important for the binding of some of the TCPs and also responsible for the crinkled leaf and silique phenotype in transgenicA. thaliana.
Irrigation water depths and soil covers in carrot crop
Authors: Vieira Joslanny Higino , Aleman Catariny Cabral , de Freitas Elis Marina , Santos Laylton de Albuquerque , da Silva Gustavo Henrique , Franco Fernandes Pedro Henrique 
Published: May 2020

AbstractThe use of soil covers may decrease water consumption and improve the crop sustainability Thus, the objective of this work was to evaluate biophysical parameters and yield of carrot crops (cultivar Brasília) grown under different irrigation water depths and soil cover conditions. The experiment was conducted at the Federal University of Viçosa, MG, Brazil. A randomized block design with four replications was used, in a 5×3 factorial arrangement.The treatments consisted of 5 irrigation water depths, based on the actual soil water capacity (20, 40, 60, 80, and 100% ASWC) and 3 soil covers (white polyethylene, biodegradable semi-kraft paper, and no soil cover - Control). The soil and leaf temperatures, number of leaves, root length, normalized difference vegetation index (NDVI), and fresh root weight were evaluated. The data were subjected to analysis of variance through the F test and the means compared by the Tukey’s test (p≤0.05); regression analysis was carried out using the equation with the highest significant fit. The use of semi-kraft paper was a good option for the carrot crop; and the water depths of up to 60% ASWC did not hinder the crop.
Novel R-type Lectin Domain-Containing Cytotoxins Comprise a Family of Virulence-Modifying Proteins in PathogenicLeptospira
Authors: Chaurasia Reetika , Marroquin Alan , Matthias Michael A. , Vinetz Joseph M. 
Published: May 2020

AbstractLeptospirosis is a globally important neglected zoonotic disease subject to both small scale outbreaks and weather-driven, large-scale epidemics. Due to gaps in our understanding ofLeptospirabiology, pathogenetic mechanisms of leptospirosis remain largely unknown. Previous data suggest that a gene family, PF07598, unique amongst most known bacterial pathogens and encoding so-called “Virulence-Modifying (VM)” proteins, are important virulence determinants. Here, we show that VM proteins are potent cytotoxins, sharing a distinct domain organization while exhibiting varied mechanisms of cellular toxicity. Structural homology searches using Phyre2 suggest that VM proteins are novel R-type lectins containing an N-terminal ricin B chain-like domain. As is known for native ricin B-chain, recombinant full-lengthrLA3490(most highly up-regulatedin vivo) and an N-terminal fragment,t3490, containing a partial ricin B-domain, bound to asialofetuin and directly competed for asialofetuin binding with recombinant ricin B chain. Whilet3490bound to the HeLa cell surface but was neither internalized nor cytotoxic,rLA3490bound to the HeLa cell surface, was rapidly internalized, translocated to the nucleus inducing chromosomal fragmentation, and was rapidly cytolethal, providing strong evidence thatLeptospiraVM proteins arebona fidecytotoxins. Because monoclonal antibodies impeding cell entry or intracellular trafficking of ricin holotoxin clearly mitigate its toxicity, that VM proteins share binding and intracellular trafficking mechanisms suggests that anti-VM-protein antibody-based (anti-toxin) therapeutics could ameliorate severe complications of leptospirosis thereby improving prognosis. As most VM proteins are restricted to high-virulenceLeptospiraspecies with some, e.g., LA3490, being exceptionally potent, their level in serum might be a potentially useful indicator of a poor prognosis, thus identifying high risk patients.Author SummaryThe PF07598 gene family encoding Virulence-Modifying (VM) proteins in pathogenicLeptospiraspecies is associated with severe manifestations of leptospirosis. Structural homology searches indicate that VM proteins contain an N-terminal ricin B chain-like domain, biochemically confirmed in asialofetuin binding and competitive-binding assays suggesting that VM proteins bind to terminal galactosyl residues of this model ricin B domain binding protein. The leptospiral N-terminal ricin B chain-like domain mediated VM protein binding to HeLa cells. Full-length recombinant protein rapidly led to cell death. Amino acid conservation among PF07598 family members at the N-terminal ricin B chain-like domain suggests that VM protein levels in serum might be a useful biomarker for quickly identifying at-risk patients, and that novel “anti-toxin”-based therapeutics could ameliorate severe complications of leptospirosis, both of which remain to be explored.
Nucleolin is essential for rabbit hemorrhagic disease virus replication by providing a physical link in replication complex formation
Authors: Zhu Jie , Miao Qiuhong , Guo Hongyuan , Qi Ruibin , Tang Aoxing , Dong Dandan , Tang Jingyu , Tong Guangzhi , Liu Guangqing 
Published: May 2020

AbstractRabbit hemorrhagic disease virus (RHDV) is an important member of theCaliciviridaefamily and cannot be propagatedin vitro, which has greatly impeded progress of investigating its replication mechanism. Construction of an RHDV replicon system has recently provided a platform for exploring RHDV replication in host cells. Here, aided by this replicon system and using two-step affinity purification, we purified the RHDV replicase and identified its associated host factors. We identified rabbit nucleolin (NCL) as a physical link required for the formation of RHDV replication complexes (RCs), by mediating the interaction between other host proteins and the viral RNA replicase, RNA-dependent RNA polymerase (RdRp). We found that RHDV RdRp uses an amino acid (aa) region spanning residues 448–478 to directly interact with NCL’s RNA-recognition motif 2. We also found that the viral p16 protein uses a highly conserved region (35Cys–Ile–Arg–Ala38or CIRA motif) to specifically bind the N-terminal region of NCL (aa 1–110) and that RHDV p23 uses a specific domain (aa 90–145) to bind NCL’s RNA-recognition motif 1. Disrupting these protein–protein interactions severely weakened viral replication. Furthermore, NCL overexpression or knockdown significantly increased or severely impaired, respectively, RHDV replication. Collectively, these results indicate that the host protein NCL is essential for RHDV replication and plays a key role in the formation of RHDV RCs. The mechanisms by which NCL promotes viral replicase assembly reported here shed light on viral RC biogenesis and may inform antiviral therapies.Author summaryRabbit hemorrhagic disease virus (RHDV) is the causative agent of highly contagious and lethal hemorrhagic disease in the European rabbit, but the host factors involved in RHDV replication remain poorly understood. In the present study, we isolated RHDV replication complex (RC) for the first time and identified its main components. We found that nucleolin (NCL) plays a key role in the formation of the RHDV RC. NCL not only interacts with viral replicase (RdRp), it also specifically binds to other important host factors. In addition, we proved that NCL is necessary for RHDV replication because the level of RHDV replication is significantly affected by knocking down the NCL gene in cells. Together, our data suggest that RHDV completes its replication by hijacking NCL to recruit other viral proteins and host factors, thereby assembling the RC of RHDV.
Characterization of miRNAs encoded by Autographa californica nucleopolyhedrovirus
Authors: Wang Jinwen , Xing Ke , Xiong Peiwen , Liang Hai , Zhu Mengxiao , Huang Shaojuan , Zhao Jin , Yu Xinghua , Ning Xiaolian , Li Runcai , Wang Xunzhang 
Published: May 2020

AbstractTwo Autographa californica nucleopolyhedrovirus (AcMNPV) encoded miRNAs, AcMNPV-miR-1 and -miR-3, have been reported in 2013 and 2019. Here, we present an integrated investigation of AcMNPV-encoded miRNAs. Six candidate miRNAs were predicted through small RNA deep sequencing and bioinformatics, of which, five validated by experiments. Three miRNAs perfectly matched the coding sequence of viral genes. The other two are located in coding sequences of viral genes. Targets in both virus and host were predicted and subsequently tested using dual-luciferase reporter assay. The validated targets were found mainly in AcMNPV, except for the targets of AcMNPV-miR-4, which are all host genes. Based on reporter assays, the five miRNAs predominantly function by down-regulating their targets, though individual target is slightly up-regulated. The transcription start sites of these miRNAs were analyzed. Our results suggest that AcMNPV-encoded miRNAs function as fine modulators of the interactions between host and virus by regulating viral and/or host genes.Author summaryVirus-encoded miRNAs have been widely reported as modulators participating in almost all biological processes. However, amongBaculoviridae, which consists of a large family of dsDNA viruses that infect numerous beneficial insects and agricultural pests, only several have been reported encoding miRNAs. To clarify the roles of AcMNPV-encoded miRNAs in host–pathogen interactions, we employed RNA deep sequencing and series of experimental approaches identifying AcMNPV-encoded miRNAs, followed by target validation and function deduction. Among them, AcMNPV-miR-1 and AcMNPV–miR-3 have been reported in 2013 and 2019, respectively. This study reveals the sites of these miRNAs in the genome, both in coding sequences and complements, suggesting diverse functions. These miRNAs target genes in the virus itself and in the host, largely by suppressing expression, with some enhancing it. The transcription initiations of the miRNAs were analyzed. Our results provide some insight into the finely regulated process of baculovirus infection.
A rapid, point of care red blood cell agglutination assay for detecting antibodies against SARS-CoV-2
Authors: Kruse Robert L. , Huang Yuting , Smetana Heather , Gehrie Eric A. , Amukele Tim K. , Tobian Aaron A.R. , Mostafa Heba H. , Wang Zack Z. 
Published: May 2020

AbstractThe COVID-19 pandemic has brought the world to a halt, with cases observed around the globe causing significant mortality. There is an urgent need for serological tests to detect antibodies against SARS-CoV-2, which could be used to assess the prevalence of infection, as well as ascertain individuals who may be protected from future infection. Current serological tests developed for SARS-CoV-2 rely on traditional technologies such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays, which may lack scalability to meet the demand of hundreds of millions of antibody tests in the coming year. Herein, we present an alternative method of antibody testing that just depends on one protein reagent being added to patient serum/plasma or whole blood and a short five-minute assay time. A novel fusion protein was designed that binds red blood cells (RBC) via a single-chain variable fragment (scFv) against the H antigen and displays the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on the surface of RBCs. Upon mixing of the fusion protein, RBD-scFv with recovered COVID-19 patient serum and RBCs, we observed agglutination of RBCs, indicating the patient developed antibodies against SARS-CoV-2 RBD. Given that the test uses methods routinely used in hospital clinical labs across the world, we anticipate the test can be rapidly deployed with only the protein reagent required at projected manufacturing cost at U.S. cents per test. We anticipate our agglutination assay may find extensive use in low-resource settings for detecting SARS-CoV-2 antibodies.