bluuebunny/crossref_metadata_2025_split huggingface dataset:
High prevalence of Human Papillomavirus (HPV) type 66 in low-grade cervical lesions of Mexican women
Authors: Juárez-González Karina , Paredes-Cervantes Vladimir , Gordillo-Rodríguez Silvia , González-Guzmán Saúl , Moncayo-Valencia Xochilt , Méndez-Martínez Rocío , García-Carrancá Alejandro , Martínez-Ezquerro José Darío , Rivas-Ruiz Rodolfo , Sánchez-Suárez Patricia , Álvarez-Sandoval Paola , Padilla-Arrieta Patricia , Martínez-Salazar Martha , Vázquez-Vega Salvador 
Published: January 2020

AbstractBackgroundHPV-16 infections constitute the highest risk for developing uterine cervix cancer. However, the role of other high-risk types is still controversial.ObjectiveTo analyze HR-HPV prevalence and its possible associations between HPV and risk factors related to cervical lesions among Mexican women.MethodsCross sectional study using 362 cervical samples collected between 2016 and 2017. Fourteen HR-HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) were detected by highly sensitive PCR amplification followed by reverse hybridization. Bivariate and multivariate analyses were performed to investigate the association between HPV types and risk factors among lesions.ResultsMost samples were HR-HPV positive (83.43%). HPV-16 was the most prevalent infection among negative for intraepithelial lesions or malignancy (78.6%), high-grade squamous intraepithelial lesions (50%), and cervical cancer (58.2%). HPV-66 showed an unexpected high prevalence in atypical squamous cells of undetermined significance (50%), low-grade squamous intraepithelial (45.7%), and only found in 3.6% of cervical cancers. HPV-16 was significantly prevalent among women between 30-39 years, whereas types 66 and 52 were significantly associated when previously sexually transmitted disease had occurred (p< 0.05).ConclusionsHPV-66 either in single or co-infection with other HR-HPV types (excluding 16 and 18) might be indicative of non-progressive cancer lesions. HPV-66 prevalence was unusually high in low-grade cervical lesions, predominantly in co-infection with HPV-51, and very low among cervical cancer. This should be addressed to interpret results obtained by methods that group type 66 with other HR-types.
Clinical presentation and differential splicing ofSRSF2, U2AF1andSF3B1mutations in patients with Acute Myeloid Leukaemia
Authors: Bamopoulos Stefanos A. , Batcha Aarif M. N. , Jurinovic Vindi , Rothenberg-Thurley Maja , Janke Hanna , Ksienzyk Bianka , Philippou-Massier Julia , Graf Alexander , Krebs Stefan , Blum Helmut , Schneider Stephanie , Konstandin Nikola , Sauerland Maria Cristina , Görlich Dennis , Berdel Wolfgang E. , Woermann Bernhard J. , Bohlander Stefan K. , Canzar Stefan , Mansmann Ulrich , Hiddemann Wolfgang , Braess Jan , Spiekermann Karsten , Metzeler Klaus H. , Herold Tobias 
Published: January 2020

AbstractPrevious studies demonstrated that splicing factor mutations are recurrent events in hematopoietic malignancies with both clinical and functional implications. However, their aberrant splicing patterns in acute myeloid leukaemia remain largely unexplored. In this study we characterized mutations inSRSF2, U2AF1andSF3B1, the most commonly mutated splicing factors. In our clinical analysis of 2678 patients, splicing factor mutations showed inferior relapse-free and overall survival, however, these mutations did not represent independent prognostic markers. RNA-sequencing of 246 and independent validation in 177 patients revealed an isoform expression profile highly characteristic for each individual mutation, with several isoforms showing a strong dysregulation. By establishing a custom differential splice junction usage pipeline we accurately detected aberrant splicing in splicing factor mutated samples. Mutated samples were characterized predominantly by decreased junction usage. A large proportion of differentially used junctions were novel. Targets of splicing dysregulation included several genes with a known role in leukaemia. InSRSF2(P95H) mutants we further explored the possibility of a cascading effect through the dysregulation of the splicing pathway. We conclude that splicing factor mutations do not represent independent prognostic markers. However, they do have genome-wide consequences on gene splicing leading to dysregulated isoform expression of several genes.
Bayesian inference for biophysical neuron models enables stimulus optimization for retinal neuroprosthetics
Authors: Oesterle Jonathan , Behrens Christian , Schröder Cornelius , Herrmann Thoralf , Euler Thomas , Franke Katrin , Smith Robert G , Zeck Günther , Berens Philipp 
Published: January 2020

ABSTRACTMulticompartment models have long been used to study the biophysical mechanisms underlying neural information processing. However, it has been challenging to infer the parameters of such models from data. Here, we build on recent advances in Bayesian simulation-based inference to estimate the parameters of detailed models of retinal neurons whose anatomical structure was based on electron microscopy data. We demonstrate how parameters of a cone, an OFF- and an ON-cone bipolar cell model can be inferred from standard two-photon glutamate imaging with simple light stimuli. The inference method starts with a prior distribution informed by literature knowledge and yields a posterior distribution over parameters highlighting parameters consistent with the data. This posterior allows determining how well parameters are constrained by the data and to what extent changes in one parameter can be compensated for by changes in another. To demonstrate the potential of such data-driven mechanistic neuron models, we created a simulation environment for external electrical stimulation of the retina as used in retinal neuroprosthetic devices. We used the framework to optimize the stimulus waveform to selectively target OFF- and ON-cone bipolar cells, a current major problem of retinal neuroprothetics. Taken together, this study demonstrates how a data-driven Bayesian simulation-based inference approach can be used to estimate parameters of complex mechanistic models with high-throughput imaging data.
Enriching and aggregating purple non-sulfur bacteria in an anaerobic sequencing-batch photobioreactor for nutrient capture from wastewater
Authors: Cerruti Marta , Stevens Berber , Ebrahimi Sirous , Alloul Abbas , Vlaeminck Siegfried E. , Weissbrodt David G. 
Published: January 2020

AbstractPurple non-sulfur bacteria (PNSB), a guild of anoxygenic photomixotrophic organisms, rise interest to capture nutrients from wastewater in mixed-culture bioprocesses. One challenge targets the aggregation of PNSB biomass through gravitational separation from the treated water to facilitate its retention and accumulation, while avoiding the need for membranes. We aimed to produce an enriched, concentrated, well-settling, nutrient-removing PNSB biomass using sequencing batch regimes (SBR) in an anaerobic photobioreactor. The stirred tank was fed with a synthetic influent mimicking loaded municipal wastewater (430-860 mg CODAcLInf-1, COD:N:P ratio of 100:36:4-100:11:2 m/m/m), operated at 30°C and pH 7, and continuously irradiated with infrared (IR) light (>700 nm) at 375 W m-2. After inoculation with activated sludge at 0.1 g VSS L-1, PNSB were rapidly enriched in a first batch of 24 h: the genusRhodobacterreached 54% of amplicon sequencing read counts. SBR operations at volume exchange ratio of 50% with decreasing hydraulic retention times (48 to 16 h; 1 to 3 cycles d-1) and increasing volumetric organic loading rates (0.2 to 1.3 kg COD m-3d-1) stimulated the aggregation (compact granules of 50-150 μm), settling (sedimentation G-flux of 4.7 kg h-1m-2), and accumulation (as high as 3.8 g VSS L-1) of biomass. The sludge retention time (SRT) increased freely from 2.5 to 11 d without controlled sludge wasting. Acetate, ammonium, and orthophosphate were removed simultaneously (up to 96% at a rate of 1.1 kg COD m-3d-1, 77% at 113 g N m-3d-1, and 73% at 15 g P m-3d-1) with a COD:N:P assimilation ratio of 100:6.7:0.9 (m/m/m). Competition for substrate and photons occurred in the PNSB guild. SBR regime shifts sequentially selected forRhodobacter(90%) under shorter SRT and non-limiting acetate concentrations during reaction phases,Rhodopseudomonas(70%) under longer SRT and acetate limitation, andBlastochloris(10%) under higher biomass concentrations. We highlighted the benefits of a PNSB-based SBR process for biomass accumulation and simultaneous nutrient capture at substantial rates, and its underlying microbial ecology.Graphical abstractHighlightsPNSB were highly enriched (90%) in an anaerobic stirred-tank photobioreactor.The mixed-culture SBR process fostered PNSB biomass aggregation and accumulation.PNSB sludge reached 3.8 g VSS L-1and a sedimentation G-flux of 4.7 kg h-1m-2.PNSB enabled a high simultaneous removal of COD (96%), N (77%), and P (73%).Rhodobacter,Rhodopseudomonas, andBlastochloriscompeted for acetate and photons.
Motile ghosts of the halophilic archaeon,Haloferax volcanii
Authors: Kinosita Yoshiaki , Mikami Nagisa , Li Zhengqun , Braun Frank , Quax Tessa EF. , van der Does Chris , Ishmukhametov Robert , Albers Sonja-Verena , Berry Richard M. 
Published: January 2020

SummaryMotility is seen across all domains of life1. Prokaryotes exhibit various types of motilities, such as gliding, swimming, and twitching, driven by supramolecular motility machinery composed of multiple different proteins2. In archaea only swimming motility is reported, driven by the archaellum (archaeal flagellum), a reversible rotary motor consisting of a torque-generating motor and a helical filament which acts as a propeller3,4. Unlike the bacterial flagellar motor (BFM), adenosine triphosphate (ATP) hydrolysis probably drives both motor rotation and filamentous assembly in the archaellum5,6. However, direct evidence is still lacking due to the lack of a versatile model system. Here we present a membrane-permeabilized ghost system that enables the manipulation of intracellular contents, analogous to the triton model in eukaryotic flagella7and glidingMycoplasma8,9. We observed high nucleotide selectivity for ATP driving motor rotation, negative cooperativity in ATP hydrolysis and the energetic requirement for at least 12 ATP molecules to be hydrolyzed per revolution of the motor. The response regulator CheY increased motor switching from counterclockwise (CCW) to clockwise (CW) rotation, which is the opposite of a previous report10. Finally, we constructed the torque-speed curve at various [ATP]s and discuss rotary models in which the archaellum has characteristics of both the BFM and F1-ATPase. Because archaea share similar cell division and chemotaxis machinery with other domains of life11,12, our ghost model will be an important tool for the exploration of the universality, diversity, and evolution of biomolecular machinery.
Neuroretinal-derived caveolin-1 promotes endotoxin-induced inflammation in the murine retina
Authors: Gurley Jami M. , Gmyrek Grzegorz , McClellan Mark E. , Hauck Stefanie M. , Dozmorov Mikhail G. , Wren Jonathan D. , Carr Daniel J. J. , Elliott Michael H. 
Published: January 2020

ABSTRACTChronic ocular inflammation is associated with many retinal degenerative diseases that result in vision loss. The immune-privileged environment and complex organization of retinal tissue allow for the retina’s essential role in visual function processes, yet confound inquiries into cell-specific inflammatory effects that lead to retinal dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in many retinal cell populations and has been implicated in retinal immune regulation. However, the direction (i.e., promotion or inhibition) in which Cav1 regulates inflammatory processes in the retina (as well as in other tissues) remains unclear. Previously, we showed that global-Cav1 depletion in the retina paradoxically resulted in reduced retinal inflammatory cytokine production with concurrent elevated retinal immune cell infiltration. We hypothesized that our previous results could be explained by cell-specific Cav1 functions in the retina. Here, we utilized our Chx10 (visual system homeobox 2)-Cre knockout model to deplete Cav1 specifically in the neural retinal (NR) compartment in order to clarify the role of neural retinal-specific Cav1 (NR-Cav1) in the retinal immune response to intravitreal LPS (lipopolysaccharide) challenge. Our data support that neural retinal-derived Cav1promotesretinal tissue inflammation as Chx10-mediated Cav1 depletion was sufficient to suppressbothretinal cytokine production and immune cell infiltration following inflammatory stimulation. Additionally, we identify Traf3 (tumor necrosis factor (TNF) receptor-associated factor 3) as a highly expressed potential immune modulator in retinal tissue that is upregulated with NR-Cav1 depletion. Furthermore, this study highlights the importance for understanding the role of Cav1 (and other proteins) in cell-specific contexts.
Interruption of thymic activity in adults improves responses to tumor immunotherapy
Authors: Almeida-Santos José , Bergman Marie-Louise , Cabral Inês Amendoeira , Demengeot Jocelyne 
Published: January 2020

AbstractThe thymus produces precursors of both effectors and regulatory T cells (Tconv and Treg, respectively) whose interactions prevents autoimmunity while allowing efficient protective immune responses. Tumors express a composite of self- and tumor-specific antigens and engage both Tconv and Treg cells. Along the aging process, the thymus involutes, and tumor incidence increases, a correlation proposed previously to be causal and the result of effector cell decline. In this work, we directly tested whether interruption of thymic activity in adult mice affects Foxp3 expressing Treg composition and function, and alters tumor immune surveillance. Young adult mice, on two different genetic backgrounds, were surgically thymectomized (TxT) and analyzed or challenged 2 months later. Cellular analysis revealed a 10-fold decrease in both Tconv and Treg numbers and a bias for activated cells. The persisting Treg displayed reduced stability of Foxp3 expression and, as a population, showed compromised return to homeostasis upon induced perturbations. We next tested the growth of three tumor models from different origin and presenting distinct degrees of spontaneous immunogenicity. In none of these conditions adult TxT facilitated tumor growth. Rather TxT enhanced the efficacy of anti-tumor immunotherapies targeting Treg and/or the checkpoint CTLA4, as evidenced by increased frequency of responder mice and decreased intra-tumoral Treg to CD8+IFNγ+cell ratio. Together, our findings point to a scenario where abrogation of thymic activities affects preferentially the regulatory over the ridding arm of the immune activities elicited by tumors, and argues that higher incidence of tumors with age cannot be solely attributed to thymic output decline.
RAD sequencing data reveal a radiation of willow species (SalixL., Salicaceae) in the Hengduan Mountains and adjacent areas
Authors: He Li , Wagner Natascha Dorothea , Hörandl Elvira 
Published: January 2020

AbstractThe Hengduan Mountains (HDM) in South West China are an important hotspot of plant diversity and endemism and considered to be a secondary diversification center for the woody plant genusSalix(Salicaceae). This study aimed to reconstruct the spatio-temporal evolution of theSalix Chamaetia-Vetrixclade in the HDM and to test for the occurrence of a radiation. We inferred phylogenetic relationships based on more than 34,000 RAD loci of 27 species. Phylogenetic analyses recovered a well-resolved tree topology with two major clades, the Eurasian and the HDM clade and a divergence time of c. 23.9 Ma. The HDM clade comprises two subclades. The species of the HDM clade originated in north HDM and adjacent areas and then dispersed into the south HDM, westwards to the Himalayas and eastwards to the Qinling Mountains. Niche modelling analyses revealed that during the last glacial maximum, range contractions were observed in the northern areas, while southward expansions resulted in range overlaps. The reconstruction of putative adaptive character evolution of plant height, inflorescence and flower morphology indicate that adaptations to altitudinal distribution contributed to the diversification of the HDM willows. Our data indicate that a radiation occurred in HDM within theSalix Chamaetia-Vetrixclade. Dispersal within the mountain system and to adjacent regions as well as survival in glacial refugia have shaped the biogeographical history of the clade. Differentiation along altitudinal zonation concomitant to morphological adaptations to colder climates may be important ecological factors for the high species diversity ofSalixin this area.
Drug repurposing for mitochondrial diseases using a pharmacological model of complex I deficiency in the yeastYarrowia lipolytica
Authors: Perlstein Ethan O. 
Published: January 2020

AbstractMitochondrial diseases affect 1 in 5,000 live births around the world. They are caused by inherited orde novomutations in over 350 nuclear-encoded and mtDNA-encoded genes. There is no approved treatment to stop the progression of any mitochondrial disease despite the enormous global unmet need. Affected families often self-compound cocktails of over-the-counter vitamins and generally recognized as safe nutritional supplements that have not received regulatory approval for efficacy. Finding a new use for an approved drug is called repurposing, an attractive path for mitochondrial diseases because of the reduced safety risks, low costs and fast timelines to a clinic-ready therapy or combination of therapies. Here I describe the first-ever drug repurposing screen for mitochondrial diseases involving complex I deficiency, e.g., Leigh syndrome, using the yeastYarrowia lipolyticaas a model system. Unlike the more commonly used yeastSaccharomyces cerevisiaebut like humans,Yarrowia lipolyticahas a functional and metabolically integrated respiratory complex I and is an obligate aerobe. In 384-well-plate liquid culture format without shaking,Yarrowia lipolyticacells grown in either glucose-containing media or acetate-containing media were treated with a half-maximal inhibitory concentration (3µM and 6μM, respectively) of the natural product and complex I inhibitor piericidin A. Out of 2,560 compounds in the Microsource Spectrum collection, 24 suppressors of piercidin A reached statistical significance in one or both media conditions. The suppressors include calcium channel blockers nisoldipine, amiodarone and tetrandrine as well as the farnesol-like sesquiterpenoids parthenolide, nerolidol and bisabolol, which may all be modulating mitochondrial calcium homeostasis. Estradiols and synthetic estrogen receptor agonists are the largest class of suppressors that rescue growth of piericidin-A-treatedYarrowia lipolyticacells in both glucose-containing and acetate-containing media. Analysis of structure-activity relationships suggests that estrogens may enhance bioenergetics by evolutionarily conserved interactions with mitochondrial membranes that promote mitochondrial filamentation and mitochondrial DNA replication.
Virtual screening of MAP-Tauprotein inhibitors fromSemecarpus anacardiumLinn. leaf extract for cancer prevention
Authors: Singh Rajesh Kumar , Singh Anil Kumar , Ranjan Amit , Srivastava Akhileshwar Kumar , Singh Monika , Kumar Abhishek , Dwivedi Kamal Nayan 
Published: January 2020

AbstractSemecarpus anacardiumis a well known Indian medicinal plant with various medicinal properties like hypoglycemic, antioxidant, anticancer, anti-inflammatory, anti-geriatric, antimicrobial and hair growth promoter, etc. The molecular mechanism of metabolites from fruiting bodies ofS. anacardiumagainst cancer has been described but anticancerous properties in its leaves are still unknown. The leaves were extracted in petroleum ether, ethyl acetate and methanol and assayed for anticancer activity using MTT assay. The active extract was evaluated for mode of cell death induction using EtBr-AO double staining and analyzed for phytochemical constituents using GC-MS, followed by molecular docking studies for exploration of possibility for anticancer agents and Drugability. In this study, ethyl acetate extract of leaf was found potent cytotoxic in MCF-7 cells and also induced apoptosis. It has also found the SLE is safe for normal cells. The molecular docking studies were done to explore the probable mechanism of action of the extract which showed 9 compounds are targeting the microtubule-associated protein tau (MAPT). MAPT promotes assembling and prevents disassembling to arrest the cell cycle. The overexpression of MAPT induces chemoresistance to cancerous cells against conventional drugs like paclitaxel. We have identified 17 compounds from ethyl acetate extract ofS. anacardiumleaves and drawn its chemical structure by using chembiodraw software to transform into pdb format. Further, the compounds have been subjected for molecular docking study to investigate its interactive efficiency with MAPT protein. The compound 13 had higher interactive potential to MAPT with binding energy −31.75 kcal/mol and lowest binding energy (−15.44 kcal/mol) was observed in compound 6. The present study suggested that the compounds from leaves ofS. anacardiumcould be alternative approach of conventional drug for cancer treatment with cost effective and less side effect.
Protein S-nitrosylation of Human Cytomegalovirus pp71 inhibits its ability to limit STING antiviral responses
Authors: Nukui Masatoshi , Roche Kathryn L. , Jia Jie , Fox Paul L. , Murphy Eain A. 
Published: January 2020

ABSTRACTHuman Cytomegalovirus (HCMV) is a ubiquitous pathogen that has co-evolved with its host and in doing so, is highly efficient in undermining antiviral responses that limit successful infections. As a result, HCMV infections are highly problematic in individuals with weakened or underdeveloped immune systems including transplant recipients and newborns. Understanding how HCMV controls the microenvironment of an infected cell so as to favor productive replication is of critical importance. To this end, we took an unbiased proteomics approach to identify the highly reversible, stress induced, post-translational modification (PTM), protein S-nitrosylation, on viral proteins to determine the biological impact on viral replication.We identified protein S-nitrosylation of 13 viral proteins during infection of highly permissive fibroblasts. One of these proteins, pp71, is critical for efficient viral replication, as it undermines host antiviral responses, including STING activation. By exploiting site-directed mutagenesis of the specific amino acids we identified in pp71 as protein S-nitrosylated, we found this pp71 PTM diminishes its ability to undermine antiviral responses induced by the STING pathway. Our results suggest a model in which protein S-nitrosylation may function as a host response to viral infection that limits viral spread.IMPORTANCEIn order for a pathogen to establish a successful infection, it must undermine the host cell responses inhibitory to the pathogen. As such, herpesviruses encode multiple viral proteins that antagonize each host antiviral response, thereby allowing for efficient viral replication. Human Cytomegalovirus encodes several factors that limit host countermeasures to infection, including pp71. We identified a previously unreported modification of pp71 residues within the protein are protein S-nitrosylated. Using site-directed mutagenesis, we mutated the specific sites of this modification thereby blocking this pp71 post-translational modification. In contexts where pp71 is not protein S-nitrosylated, host antiviral response was inhibited. The net result of this post-translational modification is to render a viral protein with diminished abilities to block host responses to infection. This novel work supports a model in which protein S-nitrosylation may be an additional mechanism in which a cell inhibits a pathogen during the course of infection.