bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel computational approach to reconstruct SARS-CoV-2 infection dynamics through the inference of unsampled sources of infection
Authors: Perera Deshan , Perks Ben , Potemkin Michael , Gordon Paul , Gill John , van Marle Guido , Long Quan 
Published: January 2021

ABSTRACTInfectious diseases such as the COVID19 pandemic cemented the importance of disease tracking. The role of asymptomatic, undiagnosed individuals in driving infection has become evident. Their unaccountability results in ineffective prevention. We developed a pipeline using genomic data to accurately predict a population’s transmission network complete with the inference of unsampled sources. The system utilises Bayesian phylogenetics to capture evolutionary and infection dynamics of SARS-CoV-2. It identified the effectiveness of preventive measures in Canada’s Atlantic bubble and mobile populations such as New York State. Its robustness extends to the prediction of cross-species disease transmission as we inferred SARS-CoV-2 transmission from humans to lions and tigers in New York City’s Bronx Zoo. The proposed method’s ability to generate such complete transmission networks, provides a more detailed insight into the transmission dynamics within a population. This potential frontline tool will be of direct help in “the battle to bend the curve”.
Tumor-Antagonizing Fibroblasts Secrete Prolargin as Tumor Suppressor in Hepatocellular Carcinoma
Authors: Chiavarina Barbara , Ronca Roberto , Otaka Yukihiro , Sutton Roger Bryan , Rezzola Sara , Yokobori Takehiko , Chiodelli Paola , Souche Regis , Maraver Antonio , Faa Gavino , Oyama Tetsunari , Gofflot Stephanie , Bellahcène Akeila , Detry Olivier , Delvenne Philippe , Castronovo Vincent , Nishiyama Masahiko , Turtoi Andrei 
Published: January 2021

AbstractSystemic treatment of hepatocellular carcinoma (HCC) targets the tumor microenvironment (TME) by combining immunotherapy with angiogenesis inhibitors. Cancer-associated fibroblasts (CAF) are important components of the TME, however their targeting in clinics remains challenging. To this end, the existence of tumor supressing CAF and their poor characterisation is a major conundrum. Starting from proteomics and single cell analysis, we outline CAF heterogeneity in HCC and describe a subtype of CAF that express a novel tumor-related protein prolargin. Upon secretion prolargin is deposited in the TME where its levels positively correlate with patient outcome (HR=0.37; p=0.01).In vivo, tumors with lower prolargin expression display faster progression (5-fold; p=0.01) and stronger angiogenesis. Mechanistically, aggressive HCC cells degrade prolargin using matrix metalloprotease 3 (MMP3). We show that prolargin binds and inhibits several growth factors, key to tumor progression. Inhibiting prolargin degradation combined with sorafenib, demonstrated superior tumor control compared to sorafenib treatment alone. In conclusion, prolargin-expressing CAF have tumor-antagonizing properties. Stabilizing prolargin tumoral levels should be considered for systemic therapy of HCC, involving CAF in existing TME targeting.
Amino acids targeted based metabolomics study in non-segmental Vitiligo: a pilot study
Authors: Marzabani Rezvan , Rezadoost Hassan , Chopanian Peyman , Mozafari Nikoo , Jafari Mohieddin , Mirzaie Mehdi , Karimi Mehrdad 
Published: January 2021

AbstractIntroductionVitiligo is an asymptomatic disorder that results from the loss of pigments (melanin), causing skin or mucosal depigmentation and impairs beauty.ObjectiveDue to the complexity of the pathogenesis of this disease and various theories including self-safety theory, oxidative stress, neurological theory and internal defects of melanocytes behind it, and finally, the vast role of amino acids in body metabolism and various activities of the body, amino acids targeted based metabolomics was set up to follow any fluctuation inside this disease.MethodologyThe study of amino acid profiles in plasma of people with non-segmental vitiligo using a liquid chromatography equipped with fluorescent detector was performed to find remarkable biomarkers for the diagnosis and evaluation of disease severity of patients with vitiligo. Twenty-two amino acids derivatized witho-phthalaldehyde (OPA) and fluorylmethyloxycarbonyl chloride (FMOC), were precisely determined. Next, the concentrations of these twenty-two amino acids and their corresponding molar ratios were calculated in 37 patients (including 18 females and 19 males) and corresponding 34 healthy individuals (18 females and 16 males). Using R programing, the data were completely analyzed between the two groups of patients and healthy to find suitable and reliable biomarkers.ResultsInterestingly, comparing the two groups, in the patient group, tyrosine, cysteine, the ratio of tyrosine to lysine and the ratio of cysteine to ornithine were increased while, arginine, lysine, ornithine and glycine ratios to cysteine have been decreased. These amino acids were selected for identification of patients with accuracy of detection of approximately 0.95 using the assessment of logistic regression.ConclusionThese results indicate a disruption of the production of melanin, increased immune activity and oxidative stress, which are also involved in the effects of vitiligo. Therefore, these amino acids can be used as biomarker for the evaluation of risk, prevention of complications in individuals at risk and monitoring of treatment process.
Multi-Spatial Scale Dynamic Interactions between Functional Sources Reveal Sex-Specific Changes in Schizophrenia
Authors: Iraji A. , Faghiri A. , Fu Z. , Rachakonda S. , Kochunov P. , Belger A. , Ford J.M. , McEwen S. , Mathalon D.H. , Mueller B.A. , Pearlson G.D. , Potkin S.G. , Preda A. , Turner J.A. , van Erp T.G.M. , Calhoun V.D. 
Published: January 2021

AbstractWe introduce an extension of independent component analysis (ICA), called multiscale ICA (msICA), and design an approach to capture dynamic functional source interactions within and between multiple spatial scales. msICA estimates functional sources at multiple spatial scales without imposing direct constraints on the size of functional sources, overcomes the limitation of using fixed anatomical locations, and eliminates the need for model-order selection in ICA analysis. We leveraged this approach to study sex-specific and -common connectivity patterns in schizophrenia.Results show dynamic reconfiguration and interaction within and between multi-spatial scales. Sex-specific differences occur (1) within the subcortical domain, (2) between the somatomotor and cerebellum domains, and (3) between the temporal domain and several others, including the subcortical, visual, and default mode domains. Most of the sex-specific differences belong to between-spatial scale functional interactions and are associated with a dynamic state with strong functional interactions between the visual, somatomotor, and temporal domains and their anticorrelation patterns with the rest of the brain. We observed significant correlations between multi-spatial scale functional interactions and symptom scores, highlighting the importance of multiscale analyses to identify potential biomarkers for schizophrenia. As such, we recommend such analyses as an important option for future functional connectivity studies.
A relative-motion method for parsing spatio-temporal behaviour of dyads using GPS relocation data
Authors: Vissat Ludovica Luisa , Blackburn Jason K. , Getz Wayne M. 
Published: January 2021

AbstractIn this paper, we introduce a novel method for classifying and computing the frequencies of movement modes of intra and interspecific dyads, focusing in particular on distance-mediated approach, retreat, following and side by side movement modes.Besides distance, the method includes factors such as sex, age, time of day, or season that cause frequencies of movement modes to deviate from random.We demonstrate and validate our method using both simulated and empirical data. Our simulated data were obtained from a relative-motion, biased random-walk (RM-BRW) model with attraction and repulsion circumferences. Our empirical data were GPS relocation time series collected from African elephants in Etosha National Park, Namibia. The simulated data were primarily used to validate our method while the empirical data analysis were used to illustrate the types of behavioral assessment that our methodology reveals.Our methodology facilitates automated, observer-bias-free analysis of the locomotive interactions of dyads using GPS relocation data, which is becoming increasingly ubiquitous as telemetry and related technologies improve. Our method should open up a whole new vista of behavioral-interaction type analyses to movement and behavioral ecologists.
Rapid fabrication of hydrogel micropatterns by projection stereolithography for studying self-organized developmental patterning
Authors: Zhu Ye , Sazer Daniel , Miller Jordan , Warmflash Aryeh 
Published: January 2021

AbstractSelf-organized patterning of mammalian embryonic stem cells on micropatterned surfaces has previously been established as an in vitro platform for early mammalian developmental studies, complimentary toin vivostudies. Traditional micropatterning methods, such as micro-contact printing (μCP), involve relatively complicated fabrication procedures, which restricts widespread adoption by biologists. Here, we demonstrate a rapid method of micropatterning by printing hydrogel micro-features onto a glass-bottomed culture vessel. The micro-features are printed using a projection stereolithography bioprinter yielding hydrogel structures that geometrically restrict the attachment of cells or protein. Compared to traditional, physical photomasks, a digitally tunable virtual photomask is used in the projector to generate blue light patterns that enable rapid iteration with minimal cost and effort. We show that a protocol that makes use of this method together with LN521 coating creates a surface suitable for human embryonic stem cell (hESC) attachment and growth with minimal non-specific adhesion. We further demonstrate that self-patterning of hESCs following previously published gastrulation and ectodermal induction protocols achieves results comparable with those obtained with commercially available plates (CYTOO).
Milk losses linked to udder health treatments at dairy farms with automatic milking systems
Authors: Adriaens Ines , Van Den Brulle Igor , Aernouts Ben 
Published: January 2021

AbstractMilk losses caused by intramammary infections (IMI) have a massive impact on farm profitability and sustainability. In this study, we analyzed milk losses from 4 553 treated IMI cases at 41 AMS dairy farms. Milk losses were estimated based on the difference between the expected and the true production. To estimate the unperturbed lactation curve, we applied an iterative procedure using the Wood model and a variance-dependent threshold on the milk yield residuals. We calculated milk losses both in a fixed window around the first treatment day of each IMI case and in the perturbations corresponding to this day, at cow level as well as at quarter level. In a fixed time window of day -5 to 30 around the first treatment, the absolute median milk losses per case were 101.5 kg, highly dependent on the parity and the lactation stage with absolute milk losses highest in multiparous cows and at peak lactation. Relative milk losses expressed in percentage were highest on the treatment day, and full recovery was often not reached within 30 days from treatment onset. In 62% of the cases, we found a perturbation in milk yield at cow level at the time of treatment. On average, perturbations started 8.7 days before the first treatment and median absolute milk losses increased to 128 kg milk per perturbation. Mastitis is not expected to have equal effects on the four quarters so this study additionally investigated losses in the individual udder quarters. We used a data-based method leveraging milk yield and electrical conductivity to project the presumably infected quarter and compared losses with the average of presumably non-infected quarters. Median absolute losses in a fixed 36-day window around treatment varied between 50.2 kg for front and 59.3 kg for hind infected quarters compared to respectively 24.7 and 26.3 kg for the median losses in the non-infected quarters. Also here, these losses depended on lactation stage and parity. Expressed proportionally to expected yield, the relative median milk losses in infected quarters on the treatment day were 20% higher in infected quarters with a higher variability and slower recovery. In 86% of the treated IMI cases, at least one perturbation was found at the quarter level. This analysis confirms the high impact of IMI on milk production, and the large variation between quarter losses illustrates the potential of quarter analysis for on-farm monitoring at farms with an automated milking system.HighlightsMilk losses were estimated for treated cases of intramammary infectionsMilk losses were highly variable across cases with a median of 101 kgWe found large differences between infected and non-infected quartersQuantification of milk losses can be the basis for better udder health management
Single Cell RNA-seq and Mass Cytometry Reveals a Novel and a Targetable Population of Macrophages in Idiopathic Pulmonary Fibrosis
Authors: Ayaub EA , Poli S , Ng J , Adams T , Schupp J , Quesada-Arias L , Poli F , Cosme C , Robertson M , Martinez-Manzano J , Liang X , Villalba J , Lederer J , Chu SG , Raby BA , Washko G , Coarfa C , Perrella MA , El-Chemaly S , Kaminski N , Rosas IO 
Published: January 2021

AbstractIn this study, we leveraged a combination of single cell RNAseq, cytometry by time of flight (CyTOF), and flow cytometry to study the biology of a unique macrophage population in pulmonary fibrosis. Using the profiling data from 312,928 cells derived from 32 idiopathic pulmonary fibrosis (IPF), 29 healthy control and 18 chronic obstructive pulmonary disease (COPD) lungs, we identified an expanded population of macrophages in IPF that have a unique transcriptional profile associated with pro-fibrotic signature. These macrophages attain a hybrid transitional state between alveolar and interstitial macrophages, are enriched with biological processes of pro-fibrotic immune cells, and express novel surface markers and genes that have not been previously reported. We then applied single cell CyTOF to simultaneously measure 37 markers to precisely phenotype the uniquely expanded macrophage subset in IPF lungs. The SPADE algorithm independently identified an expanded macrophage cluster, and validated CD84 and CD36 as novel surface markers that highly label this cluster. Using a separate validation cohort, we confirmed an increase in CD84++CD36++macrophage population in IPF compared to control and COPD lungs by flow cytometry. Further, using the signature from the IPF-specific macrophages and the LINCS drug database, we predicted small molecules that could reverse the signature of IPF-specific macrophages, and validated two molecules, CRT and Cucur, using THP-1 derived human macrophages and precision-cut lung slices (PCLS) from IPF patients. Utilizing a multi-dimensional translational approach, our work identified a novel and targetable population of macrophages found in end-stage pulmonary fibrosis.One Sentence SummarySingle cell RNAseq, CyTOF, and flow cytometry reveal the presence of an aberrant macrophage population in pulmonary fibrosis
Lipid distributions and transleaflet cholesterol migration near heterogeneous surfaces in asymmetric bilayers
Authors: Cino Elio A. , Borbuliak Mariia , Hu Shangnong , Tieleman D. Peter 
Published: January 2021

AbstractSpecific and nonspecific protein-lipid interactions in cell membranes have important roles in an abundance of biological functions. We have used coarse-grained (CG) molecular dynamics (MD) simulations to assess lipid distributions and cholesterol flipping dynamics around surfaces in a model asymmetric plasma membrane containing one of six structurally distinct entities: aquaporin-1 (AQP1), the bacterial β-barrel outer membrane proteins OmpF and OmpX, KcsA potassium channel, WALP23 peptide, and a carbon nanotube (CNT). Our findings revealed varied lipid partitioning and cholesterol flipping times around the different solutes, and putative cholesterol binding sites in AQP1 and KcsA. The results suggest that protein-lipid interactions can be highly variable, and that surface-dependant lipid profiles are effectively manifested in CG simulations with the Martini force field.
Naturally occurring combinations of receptors from single cell transcriptomics in endothelial cells
Authors: Domanskyi Sergii , Hakansson Alex , Meng Michelle , Pham Benjamin K , Graff Zivin Joshua S. , Piermarocchi Carlo , Paternostro Giovanni , Ferrara Napoleone 
Published: January 2021

ABSTRACTVEGF inhibitor drugs have been successful, especially in ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for more effective therapies of angiogenesis-related diseases. In this paper we describe naturally occurring combinations of receptors in endothelial cells that might help to understand how cells communicate and to identify targets for drug combinations. We also develop and share a new software tool called DECNEO to identify them.Single-cell gene expression data are used to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and humans) and enriched, within a network, of connections to up-regulated genes. This set includes several receptors previously shown to play a role in angiogenesis. Multiple statistical tests from large datasets, including an independent validation set, support the reproducibility, evolutionary conservation and role in angiogenesis of these naturally occurring combinations of receptors. We also show tissue-specific combinations and, in the case of choroid endothelial cells, consistency with both well-established and recent experimental findings, presented in a separate paper.The results and methods presented here advance the understanding of signaling to endothelial cells. The methods are generally applicable to the decoding of intercellular combinations of signals.
SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses
Authors: Wang Li , Fan Xiaoyu , Bonenfant Gaston , Cui Dan , Hossain Jaber , Jiang Nannan , Larson Gloria , Currier Michael , Liddell Jimma , Wilson Malania , Tamin Azaibi , Harcourt Jennifer , Ciomperlik-Patton Jessica , Pang Hong , Dybdahl-Sissoko Naomi , Campagnoli Ray , Shi Pei-Yong , Barnes John , Thornburg Natalie J. , Wentworth David E. , Zhou Bin 
Published: January 2021

AbstractCoinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses is inevitable as the COVID-19 pandemic continues. This study aimed to evaluate cell lines commonly used in virus diagnosis and isolation for their susceptibility to SARS-CoV-2. While multiple kidney cell lines from monkeys were susceptible and permissive to SARS-CoV-2, many cell types derived from human, dog, mink, cat, mouse, or chicken were not. Analysis of MDCK cells, which are most commonly used for surveillance and study of influenza viruses, demonstrated that they were insusceptible to SARS-CoV-2 and that the cellular barrier to productive infection was due to low expression level of the angiotensin converting enzyme 2 (ACE2) receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by over-expression of canine ACE2 in trans. Moreover, SARS-CoV-2 cell tropism did not appear to be affected by a D614G mutation in the spike protein.
Indole-3-glycerolphosphate synthase, a branchpoint for the biosynthesis of tryptophan, indole, and benzoxazinoids in maize
Authors: Richter Annett , Powell Adrian F. , Mirzaei Mahdieh , Wang Lucy J. , Movahed Navid , Miller Julia K. , Piñeros Miguel A. , Jander Georg 
Published: January 2021

AbstractThe maize (Zea mays) genome encodes three indole-3-glycerolphosphate synthase enzymes (IGPS1, 2, and 3) catalyzing the conversion of 1-(2-carboxyphenylamino)-l-deoxyribulose-5-phosphate to indole-3-glycerolphosphate. Three further maize enzymes (BX1, benzoxazinoneless 1; TSA, tryptophan synthase α subunit; and IGL, indole glycerolphosphate lyase) convert indole-3-glycerolphosphate to indole, which is released as a volatile defense signaling compound and also serves as a precursor for the biosynthesis of tryptophan and defense-related benzoxazinoids. Phylogenetic analyses showed that IGPS2 is similar to enzymes found in both monocots and dicots, whereas maize IGPS1 and IGPS3 are in monocot-specific clades. Fusions of yellow fluorescent protein (YFP) with maize IGPS enzymes and indole-3-glycerolphosphate lyases were all localized in chloroplasts. In bimolecular fluorescence complementation assays, IGPS1 interacted strongly with BX1 and IGL, IGPS2 interacted primarily with TSA, and IGPS3 interacted equally with all three indole-3-glycerolphosphate lyases. WhereasIGPS1andIGPS3expression was induced by insect feeding,IGPS2expression was not. Transposon insertions inIGPS1andIGPS3reduced the abundance of both benzoxazinoids and free indole.Spodoptera exigua(beet armyworm) larvae show improved growth onigps1mutant maize plants. Together, these results suggest that IGPS1 and IGPS3 function mainly in the biosynthesis of defensive metabolites, whereas IGPS2 may be involved in the biosynthesis of tryptophan. This metabolic channeling is similar, though less exclusive than that proposed for the three maize indole-3-glycerolphosphate lyases.
Distinct roles and actions of PDI family enzymes in catalysis of nascent-chain disulfide formation
Authors: Hirayama Chihiro , Machida Kodai , Noi Kentaro , Murakawa Tadayoshi , Okumura Masaki , Ogura Teru , Imataka Hiroaki , Inaba Kenji 
Published: January 2021

AbstractThe mammalian endoplasmic reticulum (ER) harbors more than 20 members of the protein disulfide isomerase (PDI) family that act to maintain proteostasis. Herein, we developed anin vitrosystem for directly monitoring PDI- or ERp46-catalyzed disulfide bond formation in ribosome-associated nascent chains (RNC) of human serum albumin. The results indicated that ERp46 more efficiently introduced disulfide bonds into nascent chains with short segments exposed outside the ribosome exit site than PDI. Single-molecule analysis by high-speed atomic force microscopy further revealed that PDI binds nascent chains persistently, forming a stable face-to-face homodimer, whereas ERp46 binds for a shorter time in monomeric form, indicating their different mechanisms for substrate recognition and disulfide bond introduction. Similarly to ERp46, a PDI mutant with an occluded substrate-binding pocket displayed shorter-time RNC binding and higher efficiency in disulfide introduction than wild-type PDI. Altogether, ERp46 serves as a more potent disulfide introducer especially during the early stages of translation, whereas PDI can catalyze disulfide formation in RNC when longer nascent chains emerge out from ribosome.