bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical evaluation of the Abbott Alinity SARS-CoV-2 spike-specific quantitative IgG and IgM assays in infected, recovered, and vaccinated groups
Authors: Narasimhan Madhusudhanan , Mahimainathan Lenin , Araj Ellen , Clark Andrew E. , Markantonis John , Green Allen , Xu Jing , SoRelle Jeffrey A. , Alexis Charles , Fankhauser Kimberly , Parikh Hiren , Wilkinson Kathleen , Reczek Annika , Kopplin Noa , Yekkaluri Sruthi , Balani Jyoti , Thomas Abey , Singal Amit , Sarode Ravi , Muthukumar Alagarraju 
Published: February 2021

AbstractThe COVID-19 pandemic continues to impose a significant burden on global health infrastructure. While identification and containment of new cases remains important, laboratories must now pivot and consider assessment of SARS-CoV-2 immunity in the setting of the recent availability of multiple COVID-19 vaccines. Here we have utilized the latest Abbott Alinity semi-quantitative IgM and quantitative IgG spike protein (SP) serology assays (IgMSP and IgGSP) in combination with Abbott Alinity IgG nucleocapsid (NC) antibody test (IgGNC) to assess antibody responses in a cohort of 1236 unique participants comprised of naïve, SARS-CoV-2 infected, and vaccinated (including both naïve and recovered) individuals. The IgMSP and IgGSP assays were highly specific (100%) with no cross-reactivity to archived samples recovered prior to the emergence of SARS-CoV-2, including those from individuals with seasonal coronavirus infections. Clinical sensitivity was 96% after 15 days for both IgMSP and IgGSP assays individually. When considered together, the sensitivity was 100%. A combination of NC- and SP-specific serologic assays clearly differentiated naïve, SARS-CoV-2-infected, and vaccine-related immune responses. Vaccination resulted in a significant increase in IgGSP and IgMSP titers, with a major rise in IgGSP following the booster (second) dose in the naïve group. In contrast, SARS-CoV-2 recovered individuals had several fold higher IgGSP responses than naïve following the primary dose, with a comparatively dampened response following the booster. This work illustrates the strong clinical performance of these new serological assays and their utility in evaluating and distinguishing serological responses to infection and vaccination.
Systematic Phenotyping and Characterization of the 5xFAD mouse model of Alzheimer’s Disease
Authors: Forner Stefania , Kawauchi Shimako , Balderrama-Gutierrez Gabriela , Kramár Enikö A. , Matheos Dina P. , Phan Jimmy , Javonillo Dominic I. , Tran Kristine Minh , Hingco Edna , da Cunha Celia , Rezaie Narges , Alcantara Joshua Andrei , Baglietto-Vargas David , Jansen Camden , Neumann Jonathan , Wood Marcelo A. , MacGregor Grant R. , Mortazavi Ali , Tenner Andrea J. , LaFerla Frank M. , Green Kim N. 
Published: February 2021

AbstractMouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions and therapeutics. For disorders such as Alzheimer’s disease in which numerous models are being generated, a challenging first step is to identify the most appropriate model and age to effectively evaluate new therapeutic approaches. Here we conducted a detailed phenotypic characterization of the 5xFAD model on a congenic C57BL/6J strain background, across its lifespan – including a seldomly analyzed 18-month old time point to provide temporally correlated phenotyping of this model and a template for characterization of new models of LOAD as they are generated. This comprehensive analysis included quantification of plaque burden, Aβ biochemical levels, and neuropathology, neurophysiological measurements and behavioral and cognitive assessments, and evaluation of microglia, astrocytes, and neurons. Analysis of transcriptional changes was conducted using bulk-tissue generated RNA-seq data from microdissected cortices and hippocampi as a function of aging, which can be explored at the UCI Mouse Explorer and AD Knowledge Portal. This deep-phenotyping pipeline identified novel aspects of age-related pathology in the 5xFAD model.
PEAK3 pseudokinase represents a pro-migratory and -invasive signalling scaffold
Authors: Hou Jianmei , Nguyen Elizabeth V , Surudoi Minglyanna , Roy Michael J , Patel Onisha , Lucet Isabelle S , Ma Xiuquan , Daly Roger J 
Published: February 2021

AbstractThe PEAK family of pseudokinases comprises PEAK1 and PEAK2 as well as the recently-identified PEAK3. PEAK1/2 play fundamental roles in regulating tyrosine kinase signal output and oncogenesis, while PEAK3 remains poorly-characterized. Here, we demonstrate that PEAK3 undergoes homotypic association as well as heterotypic interaction with PEAK1/2. PEAK3 also recruits ASAP1/2, Cbl and PYK2 and the adaptors Grb2 and CrkII, with binding dependent on PEAK3 dimerization. PEAK3 tyrosine phosphorylation on Y24 is also dependent on dimerization as well as Src family kinase activity, and interestingly, is decreased via PTPN12 in response to EGF treatment. Y24 phosphorylation is required for binding of Grb2 and ASAP1. Overexpression of PEAK3 in MDA-MB-231 breast cancer cells enhanced cell elongation and cell motility, while knockdown of endogenous PEAK3 decreased cell migration. In addition, overexpression of PEAK3 in PEAK1/2 compound knock-out MCF-10A breast epithelial cells enhanced acinar growth and invasion in 3D culture, with the latter phenotype dependent on PEAK3 tyrosine phosphorylation and binding of Grb2 and ASAP1. These findings characterize PEAK3 as an integral member of the PEAK family with scaffolding roles that promote cell proliferation, migration and invasion.
SARS-CoV-2 nucleocapsid protein dually regulates innate immune responses
Authors: Zhao Yinghua , Sui Liyan , Wu Ping , Wang Wenfang , Tan Guangyun , Wang Zedong , Yu Yang , Hou Zhijun , Wang Guoqing , Liu Quan 
Published: February 2021

ABSTRACTThe recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and a cytokine storm in the late stage of infection, however, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein interacted with the tripartite motif protein 25 (TRIM25), thereby dually regulating the phosphorylation and nuclear translocation of IRF3, STAT1 and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress retinoic acid-inducible gene I (RIG-I) ubiquitination and activation. Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.
Mechanical Mapping of Bioprinted Hydrogel Models by Brillouin Microscopy
Authors: Mahmodi Hadi , Piloni Alberto , Utama Robert , Kabakova Irina 
Published: February 2021

AbstractThree-dimensional (3D) bioprinting has revolutionised the field of biofabrication by delivering precise, cost-effective and a relatively simple way of engineeringin vitroliving systems in high volume for use in tissue regeneration, biological modelling, drug testing and cell-based diagnostics. The complexity of modern bioprinted systems requires quality control assessment to ensure the resulting product meets the desired criteria of structural design, micromechanical performance and long-term durability. Brillouin microscopy could be an excellent solution for micromechanical assessment of the bioprinted models during or post-fabrication since this technology is non-destructive, label-free and is capable of microscale 3D imaging. In this work, we demonstrate the application of Brillouin microscopy to 3D imaging of hydrogel microstructures created through drop-on-demand bioprinting. In addition, we show that this technology can resolve variations between mechanical properties of the gels with slightly different polymer fractions. This work confirms that Brillouin microscopy can be seen as a characterisation technology complementary to bioprinting, and in the future can be combined within the printer design to achieve simultaneous real-time fabrication and micromechanical characterisation ofin vitrobiological systems.
Grasp Aperture Corrections in Reach-to-Grasp Movements Do Not Alter Size Perception
Authors: van Polanen Vonne 
Published: February 2021

ABSTRACTWhen grasping an object, the opening between the fingertips (grip aperture) scales with the size of the object. If an object changes in size, the grip aperture has to be corrected. In this study, it was investigated whether such corrections would influence the perceived size of objects. The grasping plan was manipulated with a preview of the object, after which participants initiated their reaching movement without vision. In a minority of the grasps, the object changed in size after the preview and participants had to adjust their grasping movement. Visual feedback was manipulated in two experiments. In experiment 1, vision was restored during reach and both visual and haptic information was available to correct the grasp and lift the object. In experiment 2, no visual information was provided during the movement and grasps could only be corrected using haptic information. Participants made reach-to-grasp movements towards two objects and compared these in size. Results showed that participants adjusted their grasp to a change in object size from preview to grasped object in both experiments. However, a change in object size did not bias the perception of object size or alter discrimination performance. In experiment 2, a small perceptual bias was found when objects changed from large to small. However, this bias was much smaller than the difference that could be discriminated and could not be considered meaningful. Therefore, it can be concluded that the planning and execution of reach-to-grasp movements do not affect the perception of object size.
Engineering the Immune Adaptor Protein STING as a Biologic
Authors: Sun Xin , Ni Yun , He Yanpu , Yang Mengdi , Tani Tetsuo , Kitajima Shunsuke , Barbie David A. , Li Jiahe 
Published: February 2021

ABSTRACTActivation of the stimulator of interferon genes (STING) pathway through cyclic dinucleotides (CDNs) has been explored extensively as potent vaccine adjuvants against infectious diseases as well as to increase tumor immunogenicity towards cancer immunotherapy in solid tumors. Over the last decade, a myriad of synthetic vehicles, including liposomes, polymers, and other nanoparticle platforms, have been developed to improve the bioavailability and therapeutic efficacy of STING agonists in preclinical mouse models. In comparison to synthetic materials, protein-based carriers represent an attractive delivery platform owing to their biocompatibility, amenability to genetic engineering, and intrinsic capacity to form well-defined structures. In the present work, we have engineered the immune adaptor STING as a protein-based delivery system for efficient encapsulation and intracellular delivery of CDNs. Through genetic fusion with a protein transduction domain, the recombinant STING can spontaneously penetrate cells to markedly enhance the delivery of CDNs in a mouse vaccination model and a syngeneic mouse melanoma model. Moreover, motivated by recent findings that certain tumor cells can evade immune surveillance via loss of STING expression, we further unveiled that our STING platform can serve as a functional vehicle to restore the STING signaling in a panel of lung and melanoma cell lines with impaired STING expression. Taken together, our STING-based protein delivery platform may offer a unique direction towards targeting STING-silenced tumors as well as augmenting the efficacy of STING-based vaccine adjuvants.
Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples
Authors: Biji Abhijith , Khatun Oyahida , Swaraj Shachee , Narayan Rohan , Rajmani Raju , Sardar Rahila , Satish Deepshikha , Mehta Simran , Bindhu Hima , Jeevan Madhumol , Saini Deepak K , Singh Amit , Gupta Dinesh , Tripathi Shashank 
Published: February 2021

SUMMARYWhile our battle with the COVID-19 pandemic continues, a multitude of Omics data has been generated from patient samples in various studies, which remains to be translated. We conducted a meta-analysis of published transcriptome and proteome profiles of nasal swab and bronchioalveolar lavage fluid (BALF) samples of COVID-19 patients, to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swab/BALF samples from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Analysis of these data revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of COVID-19 disease. Furthermore, Thioredoxin gene (TXN) was identified as a significant upregulated host factor in our overlap analysis. An FDA-approved drug Auranofin, which inhibits Thioredoxin reduction, was found to mitigate SARS-CoV-2 replicationin vitroandin vivoin the hamster challenge model. Overall, this study translates COVID-19 host response Big Data into potential clinical interventions.
YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation
Authors: He Lizhi , Pratt Henry , Wei Fengxiang , Gao Mingshi , Weng Zhiping , Struhl Kevin 
Published: February 2021

ABSTRACTThe YAP and TAZ paralogues are transcriptional co-activators recruited to target sites, primarily by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB and STAT3, key factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, co-occupy many target sitesin vivovia AP-1 and (to a lesser extent) STAT3 sequence motifs, and stimulate transcriptional activation by AP-1 proteins. A few target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes. YAP/TAZ, JUNB, and STAT3 directly regulate a common set of target genes that overlap, but are distinct from, those regulated by YAP/TAZ and TEADs. The set of genes regulated by YAP/TAZ, STAT3, and JUNB is associated with poor survival in breast cancer patients with the triple-negative form of the disease.
Rotavirus as an Expression Platform of the SARS-CoV-2 Spike Protein
Authors: Philip Asha A. , Patton John T. 
Published: February 2021

AbstractRotavirus, a segmented double-stranded RNA virus, is a major cause of acute gastroenteritis in young children. The introduction of live oral rotavirus vaccines has reduced the incidence of rotavirus disease in many countries. To explore the possibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotaviruses with modified segment 7 RNAs that contained coding sequences for NSP3 and FLAG-tagged portions of the SARS-CoV-2 spike (S) protein. A 2A translational element was used to drive separate expression of NSP3 and the S product. rSA11 viruses were recovered that encoded the S-protein S1 fragment, N-terminal domain (NTD), receptor-binding domain (RBD), extended receptor-binding domain (ExRBD), and S2 core (CR) domain (rSA11/NSP3-fS1, -fNTD, -fRBD, -fExRBD, and -fCR, respectively). Generation of rSA11/fS1 required a foreign-sequence insertion of 2.2-kbp, the largest such insertion yet made into the rotavirus genome. Based on isopycnic centrifugation, rSA11 containing S sequences were denser than wildtype virus, confirming the capacity of the rotavirus to accommodate larger genomes. Immunoblotting showed that rSA11/-fNTD, -fRBD, -fExRBD, and -fCR viruses expressed S products of expected size, with fExRBD expressed at highest levels. These rSA11 viruses were genetically stable during serial passage. In contrast, rSA11/NSP3-fS1 failed to express its expected 80-kDa fS1 product, for unexplained reasons. Moreover, rSA11/NSP3-fS1 was genetically unstable, with variants lacking the S1 insertion appearing during serial passage. Nonetheless, these results emphasize the potential usefulness of rotavirus vaccines as expression vectors of portions of the SARS-CoV-2 S protein (e.g., NTD, RBD, ExRBD, and CR) with sizes smaller than the S1 fragment.ImportanceAmong the vaccines administered to children in the US and many other countries are those targeting rotavirus, a segmented double-stranded RNA virus that is a major cause of severe gastroenteritis. In this study, we have examined the feasibility of modifying the rotavirus genome by reverse genetics, such that the virus could serve as an expression vector of the SARS-CoV-2 spike protein. Results were obtained showing that recombinant rotaviruses can be generated that express domains of the SARS CoV-2 spike protein, including the receptor-binding domain (RBD), a common target of neutralizing antibodies produced in individuals infected by the virus. Our findings raise the possibility of creating a combined rotavirus-COVID-19 vaccine that could be used in place of current rotavirus vaccines.
Induction of specific antibodies, IgG-secreting plasmablasts and memory B cells following BCG vaccination
Authors: Bitencourt Julia , Wilkie Morven , Alvarez Marco Polo Peralta , Jacobs Ashley , Wright Daniel , Harris Stephanie A. , Smith Steven G. , Elias Sean , White Andrew , Sharpe Sally , O’Shea Matthew K. , McShane Helen , Tanner Rachel 
Published: February 2021

AbstractMany tuberculosis (TB) vaccine candidates are designed as a boost to BCG; an understanding of the BCG-induced immune response is therefore critical, and the opportunity to relate this to circumstances where BCG does protect may direct the design of more efficacious vaccines. While the T cell response to BCG vaccination has been well-characterised, little is known about the B cell and antibody response. We demonstrate BCG vaccine-mediated induction of specific antibodies in different human populations and macaque species which represent important preclinical models for TB vaccine development. We observe a strong correlation between antibody titres in serum versus plasma with modestly higher titres in serum. We also report for the first time the rapid and transient induction of antibody-secreting plasmablasts following BCG vaccination, together with a robust and durable memory B cell response in humans. Finally, we demonstrate a potential contribution of the antibody response to BCG vaccine-mediated control of mycobacterial growthin vitro. Taken together, our findings indicate that the humoral immune response in the context of BCG vaccination merits further attention to determine whether TB vaccine candidates could benefit from the induction of humoral as well as cellular immunity.
Macromolecular Regulators Have Matching Effects on the Phase Equilibrium and Interfacial Tension of Biomolecular Condensates
Authors: Mazarakos Konstantinos , Zhou Huan-Xiang 
Published: February 2021

ABSTRACTThe interfacial tension of phase-separated biomolecular condensates affects their fusion and multiphase organization, and yet how this important property depends on the composition and interactions of the constituent macromolecules is poorly understood. Here we use molecular dynamics simulations to determine the interfacial tension and phase equilibrium of model condensate-forming systems. The model systems consist of binary mixtures of Lennard-Jones particles or chains of such particles. We refer to the two components as drivers and regulators; the former has stronger self-interactions and hence a higher critical temperature (Tc) for phase separation. In previous work, we have shown that, depending on the relative strengths of driver-regulator interactions and driver-driver interactions, regulators can either promote or suppress phase separation (i.e., increase or decreaseTc). Here we find that the effects of regulators onTcquantitatively match the effects on interfacial tension (γ). This important finding means that, when a condensate-forming system experiences a change in macromolecular composition or a change in intermolecular interactions (e.g., by mutation or posttranslational modification, or by variation in solvent conditions such as temperature, pH, or salt), the resulting change inTccan be used to predict the change inγand vice versa. We also report initial results showing that disparity in intermolecular interactions drives multiphase coexistence. These findings provide much needed guidance for understanding how biomolecular condensates mediate cellular functions.
The effect of hydrophobic gases on the water fleaDaphnia magna
Authors: Robledo-Sánchez K. Carlo Martín , Ruiz-Suárez J. C. 
Published: February 2021

AbstractIt is well known that some hydrophobic atomic and molecular gases provoke anaesthetic effects in mammal animals. Depending on the gas, there is a Minimum Alveolar Concentration (MAC) to produce anaesthesia. The gas enters in the lungs, dissolve in the blood and reaches the brain. Where are the targets and which are the action mechanisms are subjects not fully understood yet. Very recently, we reported the effects of local anaesthetics on the swimming behaviour of the water fleaDaphnia magna(STOTEN691, 278-283, 2019). Our aim now is to report new studies on the behaviour of this aquatic invertebrate in the presence of three hydrophobic gases: xenon, nitrous oxide and krypton. However, if local anaesthetics easily dissolve in water, these gases do not. Therefore, we designed a chamber to dissolve the gases using pressures up to 50 atmospheres. Simultaneously, we were able to measure in real time the response of the animals through transparent windows able to support such high pressures. Xenon and nitrous oxide effectively induce lack of movement in the daphnids. The effective pressures EP50for xenon and nitrous oxide were and 5.2 atmospheres, respectively. Krypton does not present clear effects on the motile suppression, even after the exposure to 44 atmospheres. Our findings provide insight on the physiological effects important gases used in human medicine produce in aquatic invertebrate animals considered as potential models to study anesthesia.
Strongyloides RNA-seq Browser: a web-based software platform for on-demand bioinformatics analyses of Strongyloides species
Authors: Bryant Astra S. , DeMarco Stephanie F. , Hallem Elissa A. 
Published: February 2021

ABSTRACTSoil-transmitted gastrointestinal parasitic nematodes infect approximately 1 billion people worldwide, predominantly in low-resource communities. Skin-penetrating gastrointestinal nematodes in the genus Strongyloides are emerging as model systems for mechanistic studies of soil-transmitted helminths due to the growing availability of functional genomics tools for these species. To facilitate future genomics studies of Strongyloides species, we have designed a web-based application, the Strongyloides RNA-seq Browser, that provides an open source, user-friendly portal for accessing and analyzing Strongyloides genomic expression data. Specifically, the Strongyloides RNA-seq Browser takes advantage of alignment-free read mapping tools and R-based transcriptomics tools to re-analyze publicly available RNA sequencing datasets from four Strongyloides species: Strongyloides stercoralis, Strongyloides ratti, Strongyloides papillosus, and Strongyloides venezuelensis. This application permits on-demand exploration and quantification of gene expression across life stages without requiring previous coding experience. Here, we describe this interactive application and demonstrate how it may be used by nematode researchers to conduct a standard set of bioinformatics queries.