bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in SARS-CoV-2 seroprevalence in Massachusetts estimated from newborn screening specimens
Authors: Ma Kevin C. , Hale Jaime E. , Grad Yonatan H. , Alter Galit , Luzuriaga Katherine , Eaton Roger B. , Fischinger Stephanie , Kaur Devinder , Brody Robin , Siddiqui Sameed M. , Leach Dylan , Brown Catherine M. , Klevens R. Monina , Madoff Lawrence , Comeau Anne Marie 
Published: October 2021

AbstractBackgroundEstimating the cumulative incidence of SARS-CoV-2 is essential for setting public health policies. We leveraged de-identified Massachusetts newborn screening specimens to generate an accessible, retrospective source of maternal antibodies for estimating statewide SARS-CoV-2 seroprevalence in a non-test-seeking population.MethodsWe analyzed 72,117 newborn dried blood spots collected from November 2019 through December 2020, representing 337 towns and cities across Massachusetts. Seroprevalence was estimated for the general Massachusetts population after correcting for imperfect test specificity and nonrepresentative sampling using Bayesian multilevel regression and poststratification.ResultsStatewide seroprevalence was estimated to be 0.03% (90% credible interval (CI) [0.00, 0.11]) in November 2019 and rose to 1.47% (90% CI [1.00, 2.13]) by May 2020, following sustained SARS-CoV-2 transmission in the spring. Seroprevalence plateaued from May onwards, reaching 2.15% (90% CI [1.56, 2.98]) in December 2020. Seroprevalence varied substantially by community and was particularly associated with community percent non-Hispanic Black (β = 0.024, 90% CI [0.004, 0.044]); i.e., a 10% increase in community percent non-Hispanic Black was associated with a 27% higher odds of seropositivity. Seroprevalence estimates had good concordance with reported case counts and wastewater surveillance for most of 2020, prior to the resurgence of transmission in winter.ConclusionsCumulative incidence of SARS-CoV-2 protective antibody in Massachusetts was low as of December 2020, indicating that a substantial fraction of the population was still susceptible. Maternal seroprevalence data from newborn screening can inform longitudinal trends and identify cities and towns at highest risk, particularly in settings where widespread diagnostic testing is unavailable.SummaryThe measurement of maternal antibodies in dried blood spots collected for newborn screening offers a statewide source of SARS-CoV-2 seroprevalence data independent of case testing limitations. We analyzed 72,117 Massachusetts spots collected November 2019 – December 2020 and estimated longitudinal trends.
Label-Free SARS-CoV-2 Detection on Flexible Substrates
Authors: Paria Debadrita , Kwok Kam Sang , Raj Piyush , Zheng Peng , Gracias David H. , Barman Ishan 
Published: October 2021

AbstractOne of the most important strategies for mitigation and managing pandemics is widespread, rapid and inexpensive testing and isolation of infected patients. In this study, we demonstrate large area, label-free, and rapid testing sensor platforms fabricated on both rigid and flexible substrates for fast and accurate detection of SARS-CoV-2. SERS enhancing metal insulator metal (MIM) nanostructures are modeled using finite element simulations and then fabricated using nanoimprint lithography (NIL) and transfer printing. The SERS signal of various viral samples, including spiked saliva, was analyzed using machine learning classifiers. We observe that our approach can obtain the test results typically within 25 minutes with a detection accuracy of at least 83% for the viral samples. We envision that this approach which features large area nanopatterning, fabrication in both rigid and flexible formats for wearables, SERS spectroscopy and machine learning can enable new types of rapid, label-free biosensors for screening pathogens and managing current and future pandemics.
Multi-ethnic Investigation of Risk and Immune Determinants of COVID-19 Outcomes
Authors: Jun Tomi , Mathew Divij , Sharma Navya , Nirenberg Sharon , Huang Hsin-Hui , Kovatch Patricia , Wherry E. John , Huang Kuan-lin 
Published: October 2021

AbstractObjectivesTo compare risk factors for COVID-19 mortality among hospitalized Hispanic, Non-Hispanic Black, and White patients.DesignRetrospecitve cohort studySettingFive hosptials within a single academic health systemParticipants3,086 adult patients with self-reported race/ethnicity information presenting to the emergency department and hospitalized with COVID-19 up to April 13, 2020.Main outcome measuresIn-hospital mortalityResultsWhile older age (multivariable OR 1.06, 95% CI 1.05-1.07) and baseline hypoxia (multivariable OR 2.71, 95% CI 2.17-3.36) were associated with increased mortality overall and across all races/ethnicities, Non-Hispanic Black (median age 67, IQR 58-76) and Hispanic (median age 63, IQR 50-74) patients were younger and had different comorbidity profiles compared to Non-Hispanic White patients (median age 73, IQR 62-84; p<0.05 for both comparisons). Among inflammatory markers associated with COVID-19 mortality, there was a significant interaction between the Non-Hispanic Black population and interleukin-1-beta (interaction p-value 0.04).ConclusionsThis analysis of a multi-ethnic cohort highlights the need for inclusion and consideration of diverse popualtions in ongoing COVID-19 trials targeting inflammatory cytokines.
Assessment of the fatality rate and transmissibility taking account of undetected cases during an unprecedented COVID-19 surge in Taiwan
Authors: Yuan Hsiang-Yu , Hossain M. Pear , Wen Tzai-Hung , Wang Ming-Jiuh 
Published: October 2021

AbstractBackgroundDuring the COVID-19 outbreak in Taiwan between May 11 and June 20, 2021, the observed fatality rate (FR) was 5.3%, higher than the global average at 2.1%. The high number of reported deaths suggests that hospital capacity was insufficient. However, many unexplained deaths were subsequently identified as cases, indicating that there were a few undetected cases, hence resulting in a higher estimate of FR. Estimating the number of total infected cases or knowing how to reduce the undetected cases can allow an accurate estimation of the fatality rate (FR) and effective reproduction number (Rt).MethodsAfter adjusting for reporting delays, we estimated the number of undetected cases using reported deaths that were and were not previously detected. The daily FR and Rt were calculated using the number of total cases (i.e. including undetected cases). A logistic regression model was developed to predict the detection ratio among deaths using selected predictors from daily testing and tracing data.ResultsThe estimated true daily case number at the peak of the outbreak on May 22 was 897, which was 24.3% higher than the reported number, but the difference became less than 4% on June 9 and afterward. After taking account of undetected cases, our estimated mean FR (4.7%) was still high but the daily rate showed a large decrease from 6.5% on May 19 to 2.8% on June 6. Rt reached a maximum value of 6.4 on May 11, compared to 6.0 estimated using the reported case number. The decreasing proportion of undetected cases was associated with the increases in the ratio of the number of tests conducted to reported cases, and the proportion of cases that are contact-traced before symptom onset.ConclusionsIncreasing testing capacity and tracing efficiency can lead to a reduction of hidden cases and hence improvement in epidemiological parameter estimation.
Mispatterned motile cilia beating causes flow blockage in the epileptic brain
Authors: Faubel Regina J. , Santos Canellas Veronica S. , Gaesser Jenna , Beluk Nancy H. , Feinstein Tim N. , Wang Yong , Yankova Maya , Bindu Kalyani , King Stephen M. , Ganapathiraju Madhavi K. , Lo Cecilia W. 
Published: October 2021

AbstractBeating of motile cilia at the brain ventricular surface generates rapid flow in an evolutionary conserved pattern mediating the transport of cerebrospinal fluid, but its functional importance has yet to be demonstrated. Here we show disturbance of this transport may contribute to seizure susceptibility. Mice haploinsufficient for FoxJ1, transcription factor regulating motile cilia exhibited cilia-driven flow blockage and increased seizure susceptibility. Mutations in two epilepsy-associated kinases, Cdkl5 and Yes1, in mice resulted in similar cilia-driven flow blockage and increased seizure susceptibility. We showed this arises from disorganized cilia polarity associated with disruption in the highly organized basal body anchoring meshwork. Together these findings suggest mispatterning of cilia-generated flow may contribute to epilepsy and thus might account for seizures unresponsive to current seizure medications.One sentence summaryEpilepsy is associated with disturbance of cilia motion and mispatterning of fluid transport in the brain ventricles.
Dual Recognition of Multiple Signals in Bacterial Outer Membrane Proteins Enhance Assembly and Maintain Membrane Integrity
Authors: Germany Edward M. , Thewasano Nakajohn , Imai Kenichiro , Maruno Yuki , Bamert Rebecca S. , Stubenrauch Christopher J. , Dunstan Rhys A. , Ding Yue , Nakajima Yukari , Lai XiangFeng , Webb Chaille T. , Hidaka Kentaro , Tan Kher Shing , Shen Hsin-Hui , Lithgow Trevor , Shiota Takuya 
Published: October 2021

ABSTRACTOuter membrane proteins (OMPs) are essential components of the outer membrane of Gram-negative bacteria. In terms of protein targeting and assembly, the current dogma holds that a “β-signal” imprinted in the final β-strand of the OMP engages the β-barrel assembly machinery (BAM complex) to initiate membrane insertion and assembly of the OMP into the outer membrane. Here, we revealed an additional rule, that signals equivalent to the β-signal are repeated in other, internal β-strands within bacterial OMPs, by peptidomimetic and mutational analysis. The internal signal is needed to promote the efficiency of the assembly reaction of these OMPs. BamD, an essential subunit of the BAM complex, recognizes the internal signal and the β-signal, arranging several β-strands and partial folding for rapid OMP assembly. The internal signal-BamD ordering system is not essential for bacterial viability but is necessary to retain the integrity of the outer membrane against antibiotics and other environmental insults.TEASERBacterial outer membrane proteins are recognized and bound by BamD at specific signals located in multiple β-strands at the C-terminus of these proteins.
Orb-dependent polyadenylation contributes to PLP expression and centrosome scaffold assembly
Authors: Fang Junnan , Lerit Dorothy A. 
Published: October 2021

AbstractAs the microtubule-organizing centers (MTOCs) of most cells, centrosomes engineer the bipolar mitotic spindle required for error-free mitosis.DrosophilaPericentrin (PCNT)-like protein (PLP) is a key centrosome component that directs formation of a pericentriolar material (PCM) scaffold required for PCM organization and MTOC function. Here, we investigate the post-transcriptional regulation ofplpmRNA. We identify conserved binding sites for cytoplasmic polyadenylation element binding (CPEB) proteins within theplp3’-untranslated region and examine the role of the CPEB ortholog, oo18 RNA-binding protein (Orb), inplpmRNA regulation. Our data show Orb biochemically interacts withplpmRNA and promotes PLP protein expression. Loss oforb, but notorb2, diminishes PLP levels in embryonic extracts. Consequently, PLP localization to centrosomes and function in PCM scaffolding is compromised inorbmutant embryos, resulting in genome instability and embryonic lethality. Moreover, we find PLP over-expression can restore centrosome scaffolding and rescue the cell division defects caused byorbdepletion. Our data suggest Orb modulates PLP expression at the level ofplpmRNA polyadenylation and showcases the post-transcriptional regulation of core, conserved centrosomal mRNAs as critical for centrosome function.
Blocking chondrocyte hypertrophy in conditional Evc knockout mice does not modify osteoarthritis progression
Authors: Lamuedra Ana , Gratal Paula , Calatrava Lucía , Ruiz-Perez Víctor Luis , Palencia-Campos Adrián , Portal-Núñez Sergio , Mediero Aránzazu , Herrero-Beaumont Gabriel , Largo Raquel 
Published: October 2021

ABSTRACTBackgroundChondrocytes in osteoarthritic (OA) cartilage acquire a hypertrophic-like phenotype, where Hedgehog (Hh) signaling is pivotal. Hh overexpression causes OA-like cartilage lesions, whereas its downregulation prevents articular destruction in mouse models. Mutations in EVC and EVC2 genes disrupt Hh signaling, and are responsible for the Ellis-van Creveld syndrome skeletal dysplasia. Since Ellis-van Creveld syndrome protein (Evc) deletion is expected to hamper Hh target gene expression we hypothesized that it would also prevent OA progression avoiding chondrocyte hypertrophy. Our aim was to study Evc as a new therapeutic target in OA, and whether Evc deletion restrains chondrocyte hypertrophy and prevents joint damage in an Evc tamoxifen induced knockout (EvccKO) model of OA.MethodsOA was induced by surgical knee destabilization in wild-type (WT) and EvccKO adult mice, and healthy WT mice were used as controls (n=10 knees/group). Hypertrophic markers and Hh genes were measured by qRT-PCR, and metalloproteinases (MMP) levels assessed by western blot. Human OA chondrocytes and cartilage samples were obtained from patients undergoing knee joint replacement surgery. Cyclopamine (CPA) was used for Hh pharmacological inhibition and IL-1β as an inflammatory insult.ResultsTamoxifen induced inactivation of Evc inhibited Hh overexpression and partially prevented chondrocyte hypertrophy during OA, although it did not ameliorate cartilage damage in DMM-EvccKO mice. Hh pathway inhibition did not modify the expression of proinflammatory mediators induced by IL-1 beta in human OA chondrocytes in culture. Hypertrophic – IHH – and inflammatory – COX-2 – markers co-localized in OA cartilage samples.ConclusionsTamoxifen induced inactivation of Evc partially prevented chondrocyte hypertrophy in DMM-EvccKO mice, but it did not ameliorate cartilage damage. Our results suggest that chondrocyte hypertrophy per se is not a pathogenic event in the progression of OA.
Nuclear-injuries by aberrant dynein-forces defeat proteostatic purposes of Lewy Body Inclusions
Authors: Mansuri Shemin , Jain Aanchal , Singh Richa , Rawat Shivali , Mondal Debodyuti , Raychaudhuri Swasti 
Published: October 2021

AbstractBiogenesis of inclusion bodies (IBs) facilitates protein quality control (PQC). Canonical aggresomes execute degradation of misfolded proteins while non-degradable amyloids quarantine into Insoluble Protein Deposits. Lewy Bodies (LBs) are well-known neurodegenerative IBs of α-Synuclein associated diseases like Dementia with Lewy bodies (DLB) and Parkinson’s disease. Intriguingly, the PQC benefits and drawbacks associated with LBs remain underexplored. Here, we report that the crosstalk between LBs and aggresome-like IBs of α-Synuclein (Syn-aggresomes) buffers amyloidogenic α-Synuclein load in primary neurons and mitotic cell models. Using cellular biochemistry, genetic knockdown, and microscopy tools we find that LBs possess unorthodox PQC-capacities of self-quarantining the Syn-amyloids, and being degradable upon receding fresh amyloidogenesis. Syn-aggresomes equilibrate biogenesis of LBs by facilitating spontaneous and opportunistic turnover of soluble α-Synuclein and Syn-amyloids, respectively. However, LBs overgrow at the perinucleus once amyloidogenesis sets in and are misidentified by cytosolic BICD2 as cargos for motor-protein dynein. Simultaneously, microtubules surrounding the perinuclear LBs are distorted, misbalancing the dynein motor-force on nucleoskeleton leading to lamina injuries. Like typical Laminopathies, nucleocytoplasmic mixing, DNA-damage, and deregulated transcription of stress chaperones defeat the proteostatic purposes of LBs. We confirmed the lamina disintegrities in brain sections of Parkinson’s disease patients. Together, our study provides insights into the intricate complexities of proteostatic possibilities associated with α-Synuclein inclusions and offers understanding on the proteostasis-sensitivity of LB-containing aging neurons via lamina-injuries.Significance statementAmyloid inclusions of α-Synuclein called Lewy Bodies (LBs) are hallmark of multiple neurodegenerative diseases like Dementia with Lewy Bodies and Parkinson’s disease. A significant reason for the degeneration of LB-containing aging neurons in these diseases is their sensitivity to proteostasis stresses. We find two distinct inclusions of α-Synuclein in the same neurons/cells. First, the Syn-aggresomes titrate the biogenesis of the other i.e., the LBs, by facilitating degradation of soluble α-Synuclein. Syn-amyloids deposited in LBs remain degradable but LBs overgrow at the perinucleus once the kinetics of amyloid-biogenesis exceeds aggresome-assisted degradation of α-Synuclein. Perinuclear LBs destabilize local tubulin-meshwork and are misidentified as cargo for cytosolic motor dynein. Aberrant cytoskeleton-nucleoskeleton tension disintegrates lamina, deregulates stress-responsive transcription, and triggers proteostasis-sensitivity in LB-containing neurons.
In vitro reconstituted quorum sensing pathways enable rapid evaluation of quorum sensing inhibitors
Authors: Yu Dingchen 
Published: October 2021

ABSTRACTQuorum sensing, as inner- or inter-species microbial communication process orchestrated by diffusible autoinducers, typically results in collective pathogenic behaviours, being recognized as a promising druggable target for anti-virulence. Here, we reconstituted las and rhl quorum sensing pathways of Pseudomonas aeruginosa, mediated by acyl-homoserine lactones (AHLs) and LuxI/LuxR-family proteins, with fluorescence output in Escherichia coli cell-free expression system, offering a platform to rapidly evaluate quorum sensing inhibitors (QSIs) in vitro. Previously reported small-molecule quorum sensing inhibitors for interfering with P. aeruginosa quorum sensing systems were tested and showed mild to high on-target inhibition as well as off-target toxicity. Of note, quercetin displayed potent on-target inhibition to quorum sensing pathways as well as acceptable off-target toxicity to cell-free expression machinery. Upon our work, cell-free platform is anticipated to further facilitate automated and high-throughput drug screening, bridge in silico and in vivo drug-screening methods, and accelerate the upgrading of antimicrobial arsenal.GRAPHICAL ABSTRACT
Assassination Tango: An NLR/NLR-ID immune receptors pair of rapeseed co-operates inside the nucleus to activate cell death
Authors: Mermigka Glykeria , Amartolou Argyro , Mentzelopoulou Adriani , Astropekaki Niki , Sarris Panagiotis F. 
Published: October 2021

AbstractPlant immunity relies on cell-surface receptors and intracellular NLR immune receptors. Some plant NLRs carry integrated domains (IDs) that that mimic authentic pathogens effector targets. We report here the identification in Brassica napus of the genetically linked NLR/NLR-ID pair, BnRPR1 and BnRPR2. The NLR-ID carries two ID fusions and their mode of action conforms to the proposed “integrated sensor/decoy” model. The two NLRs interact and the heterocomplex localizes in the plant-cell nucleus and nucleolus. However, the BnRPRs pair does not operate through a negative regulation as it was previously reported for other NLR-IDs. Cell death is induced only upon co-expression of the two proteins and it is dependent on the helper genes EDS1 and NRG1. Truncations of the IDs of BnRPR1 results in cytoplasmic localization and compromises cell death activation. Expression, using the native promoter in Nicotiana species, led to a conditional cell death induction. However, this was not the case for the transgenic Arabidopsis, where no cell death was observed. In summary, we describe a new pair of NLR-IDs with interesting features in relation to its regulation and the cell death activation.
Cytonemes coordinate asymmetric signaling and organization in the Drosophila muscle progenitor niche
Authors: Patel Akshay , Wu Yicong , Han Xiaofei , Su Yijun , Maugel Tim , Shroff Hari , Roy Sougata 
Published: October 2021

ABSTRACTAsymmetric signaling and organization in the stem-cell niche determine stem-cell fates. Here, we investigate the basis of asymmetric signaling and stem-cell organization using the Drosophila wing-disc that creates an adult muscle progenitor (AMP) niche. We show that AMPs extend polarized cytonemes to contact the disc epithelial junctions and adhere themselves to the disc/niche. Niche-adhering cytonemes localize FGF-receptor to selectively adhere to the FGF-producing disc and receive FGFs in a contact-dependent manner. Activation of FGF signaling in AMPs, in turn, reinforces disc-specific cytoneme polarity/adhesion, which maintains their disc-proximal positions. Loss of cytoneme-mediated adhesion promotes AMPs to lose niche occupancy and FGF signaling, occupy a disc-distal position, and acquire morphological hallmarks of differentiation. Discrete AMP organization and diversification patterns are determined by localized expression and presentation patterns of two different FGFs in the wing-disc and their polarized target-specific distribution through niche-adhering cytonemes. Thus, cytonemes are essential for asymmetric signaling and niche-specific AMP organization.
Reproducible Propagation of Species-Rich Soil Microbiomes Suggests Robust Underlying Deterministic Principles of Community Formation
Authors: Čaušević Senka , Tackmann Janko , Sentchilo Vladimir , von Mering Christian , van der Meer Jan Roelof 
Published: October 2021

ABSTRACTMicrobiomes are typically characterised by high species diversity but it is poorly understood how such system-level complexity can be generated and propagated. Here, we used soils as a relevant model to study microbiome development. Despite inherent stochastic variation in manipulating species-rich communities, both laboratory-mixed medium complexity (21 soil bacterial isolates in equal proportions) and high-diversity natural top-soil communities followed highly reproducible succession paths, maintaining distinct soil microbiome signatures. Development trajectories and compositional states were different for communities propagated in soils than in liquid suspension. Microbiome states were maintained over multiple renewed growth cycles but could be diverged by short-term pollutant exposure. The different but robust trajectories demonstrated that deterministic taxa-inherent characteristics underlie reproducible development and self-organized complexity of soil microbiomes within their environmental boundary conditions. Our findings also have direct implications for potential strategies to achieve controlled restoration of desertified land.TEASERSpecies-rich soil microbiomes grow and propagate reproducibly despite inherent stochastic complexity, paving the way for soil restoration.