bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel drug-inducible sex-separation technique for insects
Authors: Kandul Nikolay P. , Liu Junru , Hsu Alexander D. , Hay Bruce A. , Akbari Omar S. 
Published: December 2019

ABSTRACTLarge sterile male releases are the gold standard for most insect population control methods and thus precise sex sorting is essential to the success of these technologies. Sex sorting is especially important for mosquito control because female mosquitoes bite and transmit diseases. However, current methods for insect sex sorting have deficiencies as they are error prone, low throughput, expensive, reduce male fitness, or lack cross species adaptability. Here we describe a novel drug-inducible system for insect sex-separation that demonstrates proof-of-principle for positive sex selection inD. melanogaster. The system exploits the toxicity of commonly used broad-spectrum antibiotics geneticin and puromycin and rescues only one sex. Sex specific rescue is achieved by inserting the sex-specific introns,TraFandDsxM, into the coding sequence of antibiotic resistance genes,NeoRorPuroR. We engineer a dual sex-sorter gene cassette and demonstrate sex specific, constitutive expression of NeoR and PuroR proteins in females and males, respectively. When raised on geneticin supplements, this sex-sorter line established 100% positive selection for female progeny, while the food supplemented with puromycin generated 100% male progeny. This system is 100% efficient and operates at remarkably low fitness costs inD. melanogaster. Since the described system exploits a conserved sex-specific splicing mechanism and reagents, which are active in many insects, it has the potential to be adaptable to insect species of medical and agricultural importance.GRAPHIC ABSTRACT
Effects of fluorescent glutamate indicators on neurotransmitter diffusion and uptake
Authors: Armbruster Moritz , Dulla Chris G. , Diamond Jeffrey S. 
Published: December 2019

AbstractGenetically encoded fluorescent glutamate indicators (iGluSnFRs) enable neurotransmitter release and diffusion to be visualized in intact tissue. Synaptic iGluSnFR signal time courses vary widely depending on experimental conditions and often last 10-100 times longer than the extracellular lifetime of synaptically released glutamate estimated with uptake measurements. iGluSnFR signals typically also decay much more slowly than the unbinding kinetics of the indicator. To resolve these discrepancies, here we have modeled synaptic glutamate diffusion, uptake and iGluSnFR activation to identify factors influencing iGluSnFR signal waveforms. Simulations suggested that iGluSnFR competes with transporters to bind synaptically released glutamate, delaying glutamate uptake. Accordingly, synaptic transporter currents recorded in iGluSnFR-expressing cortical astrocytes were slower than those in control astrocytes. Simulations also suggested that iGluSnFR reduces free glutamate levels in extrasynaptic spaces, likely limiting extrasynaptic receptor activation. iGluSnFR and lower-affinity variants nonetheless provide linear indications of vesicle release, underscoring their value for optical quantal analysis.
TF protein of Sindbis virus antagonizes host type I interferon responses in a palmitoylation-dependent manner
Authors: KJ. Rogers , S. Jones-Burrage , W. Maury , S. Mukhopadhyay 
Published: December 2019

AbstractSindbis virus (SINV) produces the small membrane protein TF from the 6K gene via a (−1) programmed ribosomal frameshifting. While several groups have shown that TF-deficient virus exhibits reduced virulence, mechanism(s) by which this occurs remain unknown. Here, we demonstrate a role for TF in antagonizing the host interferon response. Using wild-type and type 1 interferon receptor-deficient mice and primary cells derived from these animals, we show that TF controls the induction of the host interferon responses at early times during infection. Loss of TF production leads to elevated interferon and a concurrent reduction in viral loads with a loss of pathogenicity. Palmitoylation of TF has been shown to be important for particle assembly and morphology. We find that palmitoylation of TF also contributes to the ability of TF to antagonize host interferon responses as dysregulated palmitoylation of TF reduces virulence in a manner similar to loss of TF.
A novelArabidopsisphyllosphere residentProtomycessp. and a re-examination of genusProtomycesbased on genome sequence data
Authors: Wang Kai , Sipilä Timo , Overmyer Kirk 
Published: December 2019

ABSTRACTProtomycesis a genus of yeast-like fungi that is currently defined as plant pathogens of only the Umbelliferae (Apiaceae) and Compositae (Asteraceae) family plants. ManyProtomycesspecies have been proposed; however, there is a lack of molecular data and available specimens forProtomycesspp., just over ten species are officially accepted and only six species are preserved and available in public culture collections for examination. Phylogenetic relationships and species boundaries within this genus remain largely controversial. Recently, we isolatedProtomycesstrains from wildArabidopsis thaliana(Arabidopsis), aBrassicaceaefamily plant only distantly related to the acceptedProtomyceshosts. We have previously sequenced the genomes of all the currently public availableProtomycesspecies, together with a strain (SC29) we isolated from theArabidopsisphyllosphere. Genome-wide phylogenetic analysis suggests that SC29 occupies a unique phylogenetic position in the genusProtomyces. The SC29 genome has low average nucleotide identity values in comparison with other species genomes. As physiological evidence, SC29 has morphological characteristics and carbon assimilation patterns that distinguish it from the other sixProtomycesspecies. Analysis with several nuclear gene phylogenetic markers further confirms SC29 as a novelProtomycesspecies and suggests theact1gene DNA sequences can be used together with ITS sequences for the rapid identification ofProtomycesspecies. In our previous study, SC29 could persist on theArabidopsisphyllosphere in both short term laboratory and overwinter outdoor garden experiments andProtomycesspp. (or OTUs) were found in theArabidopsisphyllosphere at multiple sites in both Finland and Germany. We conclude that SC29 is a novelProtomycesspecies isolated fromArabidopsisand propose the name ofProtomyces arabidopsidicolasp. nov. Additionally, the genusProtomycesmay not be strictly associated with only Compositae or Umbelliferae family host plants, as evidenced by SC29 andProtomycesstrains previously isolated from plants in other families. The merging of twoProtomycesspecies found to have high genomic similarity (P. inouyeiandP. lactucaedebilis) is also proposed.
Global gene expression patterns in response to white patch syndrome: Disentangling symbiont loss from the thermal stress response in reef-building coral
Authors: Kenkel Carly D. , Mocellin Veronique J.L. , Bay Line K. 
Published: December 2019

AbstractThe mechanisms resulting in the breakdown of the coral symbiosis once the process of bleaching has been initiated remain unclear. Distinguishing symbiont loss from the abiotic stress response may shed light on the cellular and molecular pathways involved in each process. This study examined physiological changes and global gene expression patterns associated with white patch syndrome (WPS) inP. lobata, which manifests in localized bleaching independent of thermal stress. In addition, a meta-analysis of global gene expression studies in other corals and anemones was used to contrast differential regulation as a result of abiotic stress from expression patterns correlated with symbiotic state. Symbiont density, chlorophyllacontent, holobiont productivity, instant calcification rate, and total host protein content were uniformly reduced in WPS relative to healthy tissue. While expression patterns associated with WPS were secondary to fixed effects of source colony, specific functional enrichments suggest that the viral infection putatively giving rise to this condition affects symbiont rather than host cells. The meta-analysis revealed that expression patterns in WPS-affected tissues were significantly correlated with prior studies examining short-term thermal stress responses. This correlation was independent of symbiotic state, as the strongest correlations were found between WPS adults and both symbiotic adult and aposymbiotic coral larvae experiencing thermal stress, suggesting that the majority of expression changes reflect a non-specific stress response. Across studies, the magnitude and direction of expression change among particular functional enrichments suggests unique responses to stressor duration, and highlights unique responses to bleaching in an anemone model which engages in a non-obligate symbiosis.
Cdc48 Cofactor Shp1 Regulates Signal-Induced SCFMet30Disassembly
Authors: Lauinger Linda , Flick Karin , Yen James L. , Mathur Radhika , Kaiser Peter 
Published: December 2019

AbstractOrganisms can adapt to a broad spectrum of sudden and dramatic changes in their environment. These abrupt changes are often perceived as stress and trigger responses that facilitate survival and eventual adaptation. The ubiquitin proteasome system (UPS) is involved in most cellular processes. Unsurprisingly, components of the UPS also play crucial roles during various stress response programs. The budding yeast SCFMet30complex is an essential Cullin-RING ubiquitin ligase that connects metabolic and heavy metal stress to cell cycle regulation. Cadmium exposure results in the active dissociation of the F-box protein Met30 from the core ligase leading to SCFMet30inactivation. Consequently, SCFMet30substrate ubiquitylation is blocked and triggers a downstream cascade to activate a specific transcriptional stress response program. Signal-induced dissociation is initiated by autoubiquitylation of Met30 and serves as a recruitment signal for the AAA-ATPase Cdc48/p97, which actively disassembles the complex. Here we show that the UBX cofactor Shp1/p47 is an additional key element for SCFMet30disassembly during heavy metal stress. Although the cofactor can directly interact with the ATPase, Cdc48 and Shp1 are recruited independently to SCFMet30during cadmium stress. An intact UBX domain is crucial for effective SCFMet30disassembly, and a concentration threshold of Shp1 recruited to SCFMet30needs to be exceeded to initiate Met30 dissociation. The latter is likely related to Shp1-mediated control of Cdc48 ATPase activity. This study identifies Shp1 as the crucial Cdc48 cofactor for signal-induced, selective disassembly of a multi-subunit protein complex to modulate activity.Significance StatementUbiquitylation affects many important cellular processes, and has been linked to a number of human diseases. It has become a synonym for protein degradation, but ubiquitylation also has important non-proteolytic signaling functions. Understanding the molecular concepts that govern ubiquitin signaling is of great importance for development of diagnostics and therapeutics. The cadmium-induced inactivation of the SCFMet30ubiquitin ligase via the disassembly of the multi-subunit ligase complex, illustrates an example for non-proteolytic signaling pathways. Dissociation is triggered by autoubiquitylation of the F-box protein Met30, which is the recruiting signal for the highly conserved AAA-ATPase Cdc48/p97. Here we show that the UBX cofactor Shp1/p47 is important for this ubiquitin-dependent, active remodeling of a multi-protein complex in response to a specific environmental signal.
Novel splicing and open reading frames revealed by long-read direct RNA sequencing of adenovirus transcripts
Authors: Price Alexander M. , Hayer Katharina E. , Depledge Daniel P. , Wilson Angus C. , Weitzman Matthew D. 
Published: December 2019

AbstractAdenovirus is a common human pathogen that relies on host cell processes for production and processing of viral RNA. Although adenoviral promoters, splice junctions, and cleavage and polyadenylation sites have been characterized using low-throughput biochemical techniques or short read cDNA-based sequencing, these technologies do not fully capture the complexity of the adenoviral transcriptome. By combining Illumina short-read and nanopore long-read direct RNA sequencing approaches, we mapped transcription start sites and cleavage and polyadenylation sites across the adenovirus genome. The canonical viral early and late RNA cassettes were confirmed, but analysis of splice junctions within long RNA reads revealed an additional 20 novel viral transcripts. These RNAs include seven new splice junctions which lead to expression of canonical open reading frames (ORF), as well as 13 transcripts encoding for messages that potentially alter protein functions through truncations or the fusion of canonical ORFs. In addition, we also detect RNAs that bypass canonical cleavage sites and generate potential chimeric proteins by linking separate gene transcription units. Our work highlights how long-read sequencing technologies can reveal further complexity within viral transcriptomes.
Wss1 promotes replication stress tolerance by degrading histones
Authors: Maddi Karthik , Sam Daniel Kwesi , Bonn Florian , Prgomet Stefan , Tulowetzke Eric , Akutsu Masato , Lopez-Mosqueda Jaime , Dikic Ivan 
Published: December 2019

SummaryTimely completion of DNA replication is central to accurate cell division and to the maintenance of genomic stability. However, certain DNA-protein interactions can physically impede DNA replication fork progression. Cells remove or bypass these physical impediments by different mechanisms to preserve DNA macromolecule integrity and genome stability. InSaccharomyces cerevisiae, Wss1, the DNA-protein crosslink repair protease, allows cells to tolerate hydroxyurea-induced replication stress but the underlying mechanism by which Wss1 promotes this function has remained unknown. Here we report that Wss1 provides cells tolerance to replication stress by directly degrading core histone subunits that non-specifically and non-covalently bind to single-stranded DNA. Unlike Wss1-dependent proteolysis of covalent DNA-protein crosslinks, proteolysis of histones does not require Cdc48 nor SUMO-binding activities. Wss1 thus acts as a multi-functional protease capable of targeting a broad range of covalent and non-covalent DNA-binding proteins to preserve genome stability during adverse conditions.
Ribosome biogenesis is a downstream effector of the oncogenic U2AF1-S34F mutation
Authors: Akef Abdalla , McGraw Kathy , Cappell Steven D. , Larson Daniel R. 
Published: December 2019

AbstractU2AF1 forms a heterodimeric complex with U2AF2 that is primarily responsible for 3’ splice site selection. U2AF1 mutations have been identified in most cancers but are prevalent in Myelodysplastic Syndrome and Acute Myeloid Leukemia, and the most common mutation is a missense substitution of serine-34 to phenylalanine (S34F). However, the U2AF heterodimer also has a non-canonical function as a translational regulator. Here, we report that the U2AF1 S34F mutation results in specific mis-regulation of the translation initiation and ribosome biogenesis machinery, with the potential for widespread translational changes. The net result is a global increase in mRNA translation at the single cell level. Among the translationally upregulated targets of U2AF1-S34F are Nucleophosmin1 (NPM1), which is a major driver of myeloid malignancy. Depletion of NPM1 impairs the viability of wt/S34F cells and causes rRNA processing defects, thus indicating an unanticipated synthetic interaction between U2AF1, NPM1 and ribosome biogenesis. Our results establish a unique molecular phenotype for the U2AF1 mutation which recapitulates translational mis-regulation in myeloid disease.
Effect of porosity gradient on the permeability tensor
Authors: Madadi Mahyar , Müller Tobias M. 
Published: December 2019

ABSTRACTExperimental investigations often reveal that there is a correlation between porosity and permeability in rocks. The most commonly used model to predict the porosity–permeability relation is due to Kozeny–Carman or its many modifications. However, these models are problematic because they always involve an empirical constant and, in macroscopically heterogeneous porous media with non‐uniform porosity, more than one empirical constant would be required. Moreover, the tensor character of the permeability is not accounted for when the permeability is conceptualized as a plain function of the porosity. To overcome these limitations, we devise an approach by analysing the drag force in the volume averaging framework of poroelasticity. This allows us to deduce an expression for the inverse permeability tensor. It is the sum of the inverse of the permeability pertaining to a representative volume element and the second spatial derivative of porosity. Therefore, the gradient of porosity changes the permeability depending on the variations of macroscopic porosity variations. This result is thought to be relevant in applications where porosity maps are converted into permeability maps.
Prevention of postoperative abdominal adhesions using systemic enoxaparin and local diclofenac. An experimental study
Authors: Guzmán‐Valdivia Gómez Gilberto , Linares‐Rivera Eduardo , Tena‐Betancourt Eduardo , Arroyo‐Del Castillo Gerardo , Reipen Lukas 
Published: December 2019

AbstractIntroductionPostoperative abdominal adhesions (PAA) are a cause of morbidities, generating higher health care costs for patients and institutions responsible for health procurement. PAAs occur due to an imbalance between the enzymatic linkage in favour of fibrinogenesis in the cascade of coagulation, which encompasses a pathological process initiated by injury to the peritoneum amid the additional activation of inflammatory processes under tissue hypoxia. The objective of this study was to test the potential benefits of the use of subcutaneous enoxaparin plus intraperitoneal diclofenac in a porcine model.Material and MethodsUsing 32 hybrid female pigs, surgical adhesions were induced by open conventional splenectomy. The animals were divided into four groups: (I) control, irrigation with saline solution; (II) subcutaneous enoxaparine was applied; (III) intraperitoneal diclofenac; and (IV) combination of both.ResultsBy far, the greater degree of formation of abdominal adhesions occurs in the non‐treated control group I (P < .01). In contrast, in the macroscopic and histopathological report in terms of the degree of abdominal adhesion formation encountered in our assessments, the comparison among the treated groups showed no statistically significant differences among them, but asserted the preventive formation of PAA after the systemic application of enoxaparin and local diclofenac.ConclusionsSubcutaneous enoxaparine and intraperitoneal diclofenac reduced the formation of PAA significantly, but we found no synergic action in their combination.
Apoptotic and cytotoxic effects on human glioblastoma cell lines induced by essential oil Lavandula Augustifolia
Authors: Chan Siu‐Yee , Li Yi , Poon Wai‐Sang 
Published: December 2019

AbstractAimThe challenge of treating glioblastoma has been the lack of curative treatment. This study aimed to identify an effective low dose of the essential oil from Lavandula angustifolia (EOla), within a short exposure time for inhibiting growth and inducing apoptosis in glioblastoma cells.MethodsCell lines U‐87MG and U‐138MG were treated with diluted EOla (1:250 to 1:50) at 2, 4, 8 and 48 hours time points. The treated samples were compared with the negative control and DMSO vehicle control in MTT anti‐proliferation tests and flow cytometry cell sorting experiments. A positive control (DNase I) was included in the TUNEL imaging assay.ResultsOur data consistently showed that diluted EOla started inducing apoptosis at 1:250 dilution in both U‐138MG and U‐87MG samples. Significant differences in cell viability between DMSO and EOla samples were found in U‐87MG, (P = .02) and U‐138MG, (P = .003). Our flow cytometry results demonstrated that glioblastoma cells exposed to 1:100 diluted EOla for 4 hours had induced cell death in U‐87MG with 94.9% ± 2.6 apoptosis and 1.7% ± 2.2 necrosis; and in U‐138MG with 99% ± 3.3 apoptosis and 9.8% ± 3.1 necrosis.ConclusionUnadulterated pure therapeutic grade EOla at the concentration of 1:100 dilution has been shown to induce predominantly apoptosis (>95%) with limited necrosis (1%‐10%).
The fibrous sheath of tunnelled central venous catheters: A simple and reliable access for revision
Authors: Chan Kin Wai Edwin , Lee Kim Hung , Wong Hei Yi Vicky , Tsui Siu Yan Bess , Wong Yuen Shan Sammi , Pang Kristine Kit Yi , Mou Jennifer Wai Cheung , Tam Yuk Him Peter 
Published: December 2019

AbstractPurposeChildren may require the long‐term use of a central venous catheter (CVC) for treatment. Multiple revisions may be required when these catheters malfunction. We herein reported our experience of utilizing the fibrous sheath in tunnelled CVCs for the revision.MethodsA retrospective review was conducted from July 2008 to June 2018 on all children with the revision of tunnelled CVCs using the fibrous sheath.ResultsSixteen children underwent 31 revisions of a tunnelled CVC (16 Broviac/Hickman catheters, 15 Permcath for haemodialysis). The age ranged from 6 months to 16 years old (mean 3.8 years old). The indications for CVC revision included blockage (n = 14), breakage (n = 9) and dislodgement (n = 6). The mean time interval between CVC insertion and revision was 10.1 months (range: 20 days to 39 months). The fibrous sheath could be used for re‐insertion in 27 revisions (success rate: 87%). The failure was associated with the upsizing of the CVC (P = .003). In three of the four failed cases, a new CVC could be inserted by the cut‐down technique through the same venous access site. The overall success rate of CVC revision using the same venous access was 97%. There was no 30‐day postoperative infective complication.ConclusionsThe fibrous sheath of tunnelled CVCs is a reliable access for CVC re‐insertion. This helps to preserve the same venous access site for repeated revision of CVCs. This is extremely important in those children who depend on long‐term CVC usage.
CIC‐associated round cell sarcoma of the small bowel
Authors: Chan Angus C.K. , Chiu Jennifer H.F. , Lau Kevin C.N. 
Published: December 2019

AbstractSmall round cell sarcoma (SRCS) is considered a highly aggressive soft tissue tumour. The World Health Organization (WHO) has recognized a distinct subtype in view of the recently discovered CIC fusion gene. It has shown to have distinct pathophysiology and prognosis unlike Ewing sarcoma (ES) and rhabdomyosarcoma. However, due to its rarity, no standardized treatment has been concluded. We reported a case of intestinal obstruction caused by small bowel associated associated, laparotomy and small bowel resection was performed with good recovery and 1 year free disease survival. The gold standard of diagnosis with molecular confirmation is utmostly important in order to learn more about the natural history of this subtype thus formulating the best management plan.
The decreasing value of non‐SOEs’ political connections during China’s anti‐corruption campaign: evidence and mechanism
Authors: Liu Jinsong , Ying Qianwei 
Published: December 2019

AbstractIn this paper, we find that China’s anti‐corruption campaign since 2012 significantly reduces the value of political connections for non‐state‐owned enterprises (non‐SOEs). We provide evidence showing that the decline of the value of political connections for non‐SOEs is attributed mainly to the decreasing return from political connections, instead of increasing political risk. We further find that the decreasing return of the politically connected firms is driven mainly by the disappearance of the ‘resource effect’ of political connection in facilitating access to bank credit and government subsidies, but not due to the increasing cost of maintaining political connections.