bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible transmission flow of SARS-CoV-2 based on ACE2 features
Authors: Hassan Sk. Sarif , Ghosh Shinjini , Attrish Diksha , Choudhury Pabitra Pal , Uversky Vladimir N. , Uhal Bruce D. , Lundstrom Kenneth , Rezaei Nima , Aljabali Alaa A. A. , Seyran Murat , Pizzol Damiano , Adadi Parise , Soares Antonio , El-Aziz Tarek Mohamed Abd , Kandimalla Ramesh , Tambuwala Murtaza , Azad Gajendra Kumar , Sherchan Samendra P. , Baetas-da-Cruz Wagner , Takayama Kazuo , Serrano-Aroca Ángel , Chauhan Gaurav , Palu Giorgio , Brufsky Adam M. 
Published: October 2020

AbstractAngiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.
Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant
Authors: Lee Cheryl Yi-Pin , Amrun Siti Naqiah , Chee Rhonda Sin-Ling , Goh Yun Shan , Mak Tze-Minn , Octavia Sophie , Yeo Nicholas Kim-Wah , Chang Zi Wei , Tay Matthew Zirui , Torres-Ruesta Anthony , Carissimo Guillaume , Poh Chek Meng , Fong Siew-Wai , Bei Wang , Lee Sandy , Young Barnaby Edward , Tan Seow-Yen , Leo Yee-Sin , Lye David C. , Lin Raymond T. P. , Maurer-Stroh Sebastien , Lee Bernett , Cheng-I Wang , Renia Laurent , Ng Lisa F.P. 
Published: October 2020

ABSTRACTThe emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions.IMPORTANCERandom mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant.
Reliability of retinal pathology quantification in age-related macular degeneration: Implications for clinical trials and machine learning applications
Authors: Müller Philipp L. , Liefers Bart , Treis Tim , Rodrigues Filipa Gomes , Olvera-Barrios Abraham , Paul Bobby , Dhingra Narendra , Lotery Andrew , Bailey Clare , Taylor Paul , Sánchez Clarisa I. , Tufail Adnan 
Published: October 2020

ABSTRACTPurposeTo investigate the inter-reader agreement for grading of retinal alterations in age-related macular degeneration (AMD) using a reading center setting.MethodsIn this cross-sectional case series, spectral domain optical coherence tomography (OCT, Topcon 3D OCT, Tokyo, Japan) scans of 112 eyes of 112 patients with neovascular AMD (56 treatment-naive, 56 after three anti-vascular endothelial growth factor injections) were analyzed by four independent readers. Imaging features specific for AMD were annotated using a novel custom-built annotation platform. Dice score, Bland-Altman plots, coefficients of repeatability (CR), coefficients of variation (CV), and intraclass correlation coefficients (ICC) were assessed.ResultsLoss of ellipsoid zone, pigment epithelium detachment, subretinal fluid, and Drusen were the most abundant features in our cohort. The features subretinal fluid, intraretinal fluid, hypertransmission, descent of the outer plexiform layer, and pigment epithelium detachment showed highest inter-reader agreement, while detection and measures of loss of ellipsoid zone and retinal pigment epithelium were more variable. The agreement on the size and location of the respective annotation was more consistent throughout all features.ConclusionsThe inter-reader agreement depended on the respective OCT-based feature. A selection of reliable features might provide suitable surrogate markers for disease progression and possible treatment effects focusing on different disease stages.Translational RelevanceThis might give opportunities to a more time- and cost-effective patient assessment and improved decision-making as well as have implications for clinical trials and training machine learning algorithms.
Expanding the Galaxy’s reference data
Authors: VijayKrishna Nagampalli , Joshi Jayadev , Coraor Nate , Hillman-Jackson Jennifer , Bouvier Dave , van den Beek Marius , Eguinoa Ignacio , Coppens Frederik , Golitsynskiy Sergey , Stolarczyk Michał , Sheffield Nathan C. , Gladman Simon , Cuccuru Gianmauro , Grüning Björn , Soranzo Nicola , Rasche Helena , Langhorst Bradley W. , Bernt Matthias , Fornika Dan , de Lima Morais David Anderson , Barrette Michel , van Heusden Peter , Petrillo Mauro , Puertas-Gallardo Antonio , Patak Alex , Hotz Hans-Rudolf , Blankenberg Daniel 
Published: October 2020

AbstractSummaryProperly and effectively managing reference datasets is an important task for many bioinformatics analyses. Refgenie is a reference asset management system that allows to easily organize, retrieve, and share such datasets. Here, we describe the integration of refgenie into the Galaxy platform. Server administrators are able to configure Galaxy to make use of reference datasets made available on a refgenie instance. Additionally, a Galaxy Data Manager tool has been developed to provide a graphical interface to refgenie’s remote reference retrieval functionality. A large collection of reference datasets has also been made available using the CVMFS repository from GalaxyProject.org, with mirrors across the United States, Canada, Europe, and Australia, enabling easy use outside of Galaxy.Availability and implementationThe ability of Galaxy to use refgenie assets was added to the core Galaxy framework in version 20.05, which is available fromhttps://github.com/galaxyproject/galaxyunder the Academic Free License version 3.0. The refgenie Data Manager tool can be installed via the Galaxy ToolShed, with source code managed athttps://github.com/BlankenbergLab/galaxy-tools-blankenberg/tree/main/data_managers/data_manager_refgenie_pulland released using an MIT license.
A mobile genetic element increases bacterial host fitness by manipulating development
Authors: Jones Joshua M. , Grinberg Ilana , Eldar Avigdor , Grossman Alan D. 
Published: October 2020

AbstractHorizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element ofBacillus subtilis, provides to its host cells. Activation of ICEBs1conferred a frequency-dependent selective advantage to host cells during two different developmental processes: biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1gene,devI(formerlyydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1to increase host fitness, thereby increasing propagation of the element.
A red fluorescent protein with improved monomericity enables ratiometric voltage imaging with ASAP3
Authors: Kim Benjamin B. , Wu Haodi , Hao Yukun A. , Pan Michael , Chavarha Mariya , Westberg Michael , St-Pierre Francois , Wu Joseph C. , Lin Michael Z. 
Published: October 2020

AbstractA ratiometric genetically encoded voltage indicator (GEVI) would be desirable for tracking transmembrane voltage changes in cells that are undergoing motion. To create a high-performance ratiometric GEVI, we explored the possibility of adding a voltage-independent red fluorophore to ASAP3, a high-gain green fluorescent GEVI. We performed combinatorial multi-site mutagenesis on the cyan-excitable red fluorescent protein mCyRFP1 to enhance brightness and monomericity, creating mCyRFP3. Among red fluorescent proteins tested, mCyRFP3 proved to be the least perturbing when fused to ASAP3. We demonstrate that the red fluorescence of ASAP3-mCyRFP3 (ASAP3-R3) provides an effective reference channel to remove motion artifacts from voltage-induced changes in green fluorescence. Finally we use ASAP3-R3 to visualize membrane voltage changes throughout the cell cycle of motile cells.
Phenotypic and molecular evolution across 10,000 generations in laboratory budding yeast populations
Authors: Johnson Milo S. , Gopalakrishnan Shreyas , Goyal Juhee , Dillingham Megan E. , Bakerlee Christopher W. , Humphrey Parris T. , Jagdish Tanush , Jerison Elizabeth R. , Kosheleva Katya , Lawrence Katherine R. , Min Jiseon , Moulana Alief , Phillips Angela M. , Piper Julia C. , Purkanti Ramya , Rego-Costa Artur , McDonald Michael J. , Ba Alex N. Nguyen , Desai Michael M. 
Published: October 2020

AbstractLaboratory experimental evolution provides a window into the details of the evolutionary process. To investigate the consequences of long-term adaptation, we evolved 205 S. cerevisiae populations (124 haploid and 81 diploid) for ∼10,000 generations in three environments. We measured the dynamics of fitness changes over time, finding repeatable patterns of declining adaptability. Sequencing revealed that this phenotypic adaptation is coupled with a steady accumulation of mutations, widespread genetic parallelism, and historical contingency. In contrast to long-term evolution in E. coli, we do not observe long-term coexistence or populations with highly elevated mutation rates. We find that evolution in diploid populations involves both fixation of heterozygous mutations and frequent loss-of-heterozygosity events. Together, these results help distinguish aspects of evolutionary dynamics that are likely to be general features of adaptation across many systems from those that are specific to individual organisms and environmental conditions.
Rapid profiling of drug-resistant bacteria using DNA-binding dyes and a nanopore-based DNA sequencer
Authors: Ohno Ayumu , Umezawa Kazuo , Asai Satomi , Kryukov Kirill , Nakagawa So , Miyachi Hayato , Imanishi Tadashi 
Published: October 2020

AbstractSpread of drug-resistant bacteria is a serious problem worldwide. We thus designed a new sequence-based protocol that can quickly identify bacterial compositions of clinical samples and their drug-resistance profiles simultaneously. Here we utilized propidium monoazide (PMA) that prohibits DNA amplifications from dead bacteria, and subjected the original and antibiotics-treated samples to 16S rRNA metagenome sequencing. We tested our protocol on bacterial mixtures, and observed that sequencing reads derived from drug-resistant bacteria were significantly increased compared with those from drug-sensitive bacteria when samples were treated by antibiotics. Our protocol is scalable and will be useful for quickly profiling drug-resistant bacteria.
Calcium signaling through a Transient Receptor Channel is important forToxoplasma gondiigrowth
Authors: Márquez-Nogueras Karla M. , Chasen Nathan M. , Hortua Triana Myriam A. , Kuo Ivana Y. , Moreno Silvia N.J. 
Published: October 2020

ABSTRACTTransient Receptor Potential (TRP) channels participate in ion calcium (Ca2+) influx and intracellular Ca2+release. TRP channels have not been studied inToxoplasma gondiior any other Apicomplexan parasite. We characterized a protein predicted to possess a TRP domain (TgTRPPL-2) and determined its role in Ca2+signaling inT. gondii, the causative agent of toxoplasmosis. TgTRPPL-2 localized to the plasma membrane and the endoplasmic reticulum ofT. gondii. TheΔTgTRPPL-2mutant was defective in growth and Ca2+influx. Heterologous expression of TgTRPPL-2 in HEK-3KO cells allowed its functional characterization. Patching of ER-nuclear membranes demonstrated that TgTRPPL-2 is a non-selective cation channel that conducts Ca2+. Pharmacological blockers of TgTRPPL-2 inhibited Ca2+influx and parasite growth. This is the first report of an Apicomplexan channel that conducts Ca2+and initiates the Ca2+signaling cascade that culminates in the stimulation of motility, invasion and egress. TgTRPPL-2 is a potential target for combating toxoplasmosis.
Transcriptome Analysis of the Eggplant Fruits Overexpressing a Gene of Chlorogenic Acid Pathway
Authors: Kaushik Prashant 
Published: October 2020

AbstractChlorogenic acid is the primary phenolic acids present in Eggplant fruits. For the generation of chlorogenic acid in the eggplant hydroxycinnamoyl CoA-quinate transferase (SmHQT), is a central enzyme that catalyzes the reaction to the chlorogenic acid production. Although a precise function of SmHQT is not well defined in the eggplant fruit. In this study, the overexpression of SmHQT in the eggplant fruit’s flesh was studied using the agroinfiltration technique. Furthermore, to determine the differences at the genomic level RNA-seq analysis was performed, and its results showed that 415 genes of the phenylpropanoid pathway were upregulated in the transgenic fruit. Also, it was determined that the differentially expressed genes were dominantly related to phenylpropanoid pathway along with cell expansion, and cytokinin. The agroinfiltrated fruit exhibited more than twice the chlorogenic content in the normal fruit. Overall, the result provides new insight into the eggplant chlorogenic content increment at the molecular level and unseal the opportunities to design new strategies for the improvement of chlorogenic content as nutrition in eggplant.
Cross-Linking of T cell to B cell lymphoma by the T cell bispecific antibody CD20-TCB induces IFNγ/CXCL10-dependent peripheral T cell recruitment in humanized murine model
Authors: Cremasco Floriana , Menietti Elena , Speziale Dario , Sam Johannes , Sammicheli Stefano , Richard Marine , Varol Ahmet , Klein Christian , Umana Pablo , Bacac Marina , Colombetti Sara , Perro Mario 
Published: October 2020

AbstractDiffuse large B cell lymphomas (DLBCL) are a highly heterogeneous subtype of Non Hodgkin Lymphoma (NHL), accounting for about 25% of NHL [1]. Despite an increased progression-free survival upon therapy, 40-50% of patients develop relapse/refractory disease, therefore there remains an important medical need [2]. T cell recruiting therapies, such as the CD20xCD3 T cell bi-specific antibody CD20-TCB (RG6026 or glofitamab), represent a novel approach to target all stages of DLBCL, especially those that fail to respond to multiple lines of treatment [3, 4]. We aimed for a better understanding of the molecular features related to the mode of action (MoA) of CD20-TCB in inducing Target/T cell synapse formation and human T cell recruitment to the tumor. To directly evaluate the correlation between synapse, cytokine production and anti-tumor efficacy using CD20-TCB, we developed an innovative preclinical human DLBCLin vivomodel that allowed trackingin vivohuman T cell dynamics by multiphoton intravital microscopy (MP-IVM). Byex vivoandin vivoapproaches, we revealed that CD20-TCB is inducing strong and stable synapses between human T cell and tumor cells, which are dependent on the dose of CD20-TCB and on LFA-1 activity but not on FAS-L. Moreover, despite CD20-TCB being a large molecule (194.342 kDa), we observed that intra-tumor CD20-TCB-mediated human T cell-tumor cell synapses occur within 1 hour upon CD20-TCB administration. These tight interactions, observed for at least 72 hours post TCB administration, result in tumor cell cytotoxicity, resident T cell proliferation and peripheral blood T cell recruitment into tumor. By blocking the IFNγ-CXCL10 axis, the recruitment of peripheral T cells was abrogated, partially affecting the efficacy of CD20-TCB treatment which rely only on resident T cell proliferation. Altogether these data reveal that CD20-TCB’s anti-tumor activity relies on a triple effect: i) fast formation of stable T cell-tumor cell synapses which induce tumor cytotoxicity and cytokine production, ii) resident T cell proliferation and iii) recruitment of fresh peripheral T cells to the tumor core to allow a positive enhancement of the anti-tumor effect.
Natural Oil Blend Formulation (NOBF) as an anti- African Swine Fever Virus (ASFV) agent in Primary Porcine Alveolar Macrophases (PAM) cells of Swine
Authors: Babikian Haig Yousef , Jha Rajeev Kumar , Truong Quang Lam , Nguyen Lan Thi , Nguyen Hoa Thi , To Thanh Long 
Published: October 2020

ABSTRACTAfrican swine fever is one of the severe pathogens of swine. It has a significant impact on production and on economics. So far, there are no known remedies, such as vaccines or drugs, reported. The natural oil blend formulation (NOBF) successfully tested against the African swine fever virus (ASFV) inin vitroconditions. The natural oil blend formulation (NOBF) combinesEucalyptus globulus,Pinus sylvestris, andLavandula latifolia. We used a two-fold serial dilution to test the NOBF formulation dose. Thein vitrotrial results demonstrated that NOBF up to dilution 13 or 0.000625 ml deactivates the lethal dose 105HAD50 of ASFV. There was no hemadsorption (Rosetta formation) up to dilution 12 or 0.00125 ml of NOBF. The Ct value of the NOBF group at 96 hours post-infection was the same as the initial value or lower (25), whereas the Ct value of positive controls increased several folds (17.84). Thein vitrotrial demonstrated that NOBF can deactivate the African swine fever virus.HIGHLIGHTSThe natural oil blend formulation (NOBF) was formulated using three natural oils, i.e.,Eucalyptus globulus,Pinus sylvestris, andLavandula latifolia.The in vitro trial was conducted using porcine alveolar macrophages (PAMs) and further passaged in the PAMs; the stock used in the present study was that obtained after the 15th passage.The natural oil blend formulation (NOBF) showed protection against ASF virus up to a dilution of 13 or 0.000625 of a dilution of 16 or 0.000078 ml that was tried.The real-time PCR analysis showed that the virus did not replicate in the NOBF group, which implies that either ASFV growth was inhibited in the presence of NOBF or that it was inactivated.Thein vitrotrial outcome showed that NOBF has anti-ASFV properties.
Mendelian randomization identifies the potential causal impact of dietary patterns on circulating blood metabolites
Authors: Taba Nele , Valge Hanna-Kristel , Metspalu Andres , Esko Tõnu , Wilson James F. , Fischer Krista , Pirastu Nicola 
Published: October 2020

AbstractNutrition plays an important role in the development and progress of several health conditions, but the exact mechanism is often still unclear. Blood metabolites are likely candidates to be mediating these relationships, as their levels are strongly dependent on the frequency of consumption of several foods/drinks. Understanding the causal effect of food on metabolites is thus of extreme importance. To establish these effects we utilized Two-sample Mendelian randomization using the genetic variants associated with dietary traits as instrumental variables. The estimates of single-nucleotide polymorphisms’ effects on exposures were obtained from a recent genome-wide association study (GWAS) of 25 individual and 15 principal-component dietary traits, whereas the ones for outcomes were obtained from a GWAS of 123 blood metabolites measured by nuclear magnetic resonance spectroscopy. We identified 417 potentially causal links between food and metabolites, replicating previous findings, such as the association between increased oily fish consumption and higher DHA, and highlighting several novel associations. Most of the associations were related to very-low-density, intermediate-density (IDL) and low-density lipoproteins (LDL). For example, we found that constituents of IDL particles and large LDL particles were raised by coffee and alcohol while lowered by an overall healthier diet and fruit consumption. Our results represent one of the first examples of the estimates of long-term causal effects of diet on metabolites and start bridging the gap in the mechanistic understanding linking food consumption to its health consequences.
Sex-specific maturational trajectory of endocannabinoid plasticity in the rat prefrontal cortex
Authors: Bernabeu Axel , Bara Anissa , Manduca Antonia , Borsoi Milene , Lassalle Olivier , Pelissier-Alicot Anne-Laure , Manzoni Olivier JJ 
Published: October 2020

AbstractThe prefrontal cortex (PFC) develops until early adulthood in rodents and humans, but how synaptic plasticity evolves throughout postnatal development is not known. Here, we used a cross-sectional approach to establish the postnatal maturational trajectories of intrinsic properties and synaptic plasticity in the PFC of rats of both sexes. We found that while layer 5 PFC pyramidal neurons from rats of both sexes displayed similar current-voltage relationships, rheobases and resting potentials across all age groups, excitability was lower in female adults compared to the other developmental stages. NMDAR-dependent long-term potentiation and mGluR2/3-mediated long-term depression (LTD) were equally expressed at the juvenile, pubescent and adult developmental stages in animals of both sexes. However, the developmental course of endocannabinoid (eCB)-mediated LTD was sexually dimorphic. First, eCB-LTD emerged during the juvenile period in females. However, although CB1Rs were functional in both sexes at all developmental stages, eCB-LTD’s first emerged during pubescence in male. Second, eCB-LTD engaged distinct receptors in males and females depending on their developmental stages. Female rats employ both CB1R and TRPV1R to produce eCB-LTD at the juvenile stage but solely CB1R at pubescence followed by only TRPV1R at adulthood. In contrast, in pubescent and adult males eCB-LTD always and exclusively depended on CB1R. Pharmacological blockade of 2AG’s principal degrading enzyme allowed incompetent male juvenile synapses to express eCB-LTD. The data reveal different maturational trajectories in the PFC of male and female rats and provide new cellular substrates to the sex-specific behavioral and synaptic abnormalities caused by adolescent exposure to cannabinoids.