bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a quantum-dot lateral flow immunoassay strip based portable fluorescence smart-phone system for ultrasensitive detection of IgM/IgG to SARS-CoV-2
Authors: Liu Bochao , Li Jinfeng , Tang Xi , Wu Ze , Lu Jinhui , Liang Chaolan , Hou Shuiping , Zhang Ling , Li Tingting , Zhao Wei , Fu Yongshui , Ke Yuebin , Li Chengyao 
Published: July 2020

ABSTRACTBackgroundSince December 2019, the outbreak of coronavirus disease (COVID-19) has been occurred by novel coronavirus (SARS-CoV-2). The rapid and sensitive immunoassays are urgently demanded for detecting specific antibodies as assistant diagnosis for primary screening of asymptomatic individuals, close contacts, suspected or recovered patients of COIVD-19 during the pandemic period.MethodsThe recombinant receptor binding domain of SARS-CoV-2 spike protein (S-RBD) was used as the antigen to detect specific IgM and the mixture of recombinant nucleocapsid phosphoprotein (NP) and S-RBD were used to detect specific IgG by the newly designed quantum-dot lateral flow immunoassay strip (QD-LFIA), respectively.ResultsA rapid and sensitive QD-LFIA based portable fluorescence smart-phone system was developed for detecting specific IgM/IgG to SARS-CoV-2 from 100 serum samples of COVID-19 patients and 450 plasma samples from healthy blood donors. Among 100 COVID-19 patients diagnosed with NAT previously, 3 were severe, 35 mild and 62 recovered cases. By using QD-LFIA, 78 (78%) and 99 (99%) samples from 100 COVID-19 patients’ serum were detected positive for anti-SARS-CoV-2 IgM or IgG, respectively, but only one sample (0.22%) was cross-reactive with S-RBD from 450 healthy blood donor plasmas that were collected from different areas of China.ConclusionAn ultrasensitive and specific QD-LFIA based portable fluorescence smart-phone system was developed fo r detection of specific IgM and IgG to SARS-CoV-2 infection, which could be used for investigating the prevalence or assistant diagnosis of COVID-19 in humans.
Nitrapyrin has far reaching effects on the soil microbial community structure, composition, diversity and functions
Authors: Schmidt Ruth , Wang Xiao-Bo , Garbeva Paolina , Yergeau Étienne 
Published: July 2020

AbstractNitrapyrin is one of the most common nitrification inhibitors that are used to retain N in the ammonia form in soil to improve crop yields and quality. Whereas the inhibitory effect of nitrapyrin is supposedly specific to ammonia oxidizers, in view of the keystone role of this group in soils, nitrapyrin could have far-reaching impacts. Here, we tested the hypothesis that nitrapyrin leads to large shifts in soil microbial community structure, composition, diversity and functions, beyond its effect on ammonia-oxidizers. To test this hypothesis, we set-up a field experiment where wheat (Triticum aestivumcv. AC Walton) was fertilized with ammonium nitrate (NH4NO3) and supplemented or not with nitrapyrin. Rhizosphere and bulk soils were sampled twice, DNA was extracted, the 16S rRNA gene and ITS region were amplified and sequenced to follow shifts in archaeal, bacterial and fungal community structure, composition and diversity. To assess microbial functions, several genes involved in the nitrogen cycle were quantified by real-time qPCR and volatile organic compounds (VOCs) were trapped in the rhizosphere at the moment of sampling. As expected, sampling date and plant compartment had overwhelming effects on the microbial communities. However, within these strong effects, we found statistically significant effects of nitrapyrin on the relative abundance of Thaumarchaeota, Proteobacteria, Nitrospirae and Basidiomycota, and on several genera. Nitrapyrin also significantly affected bacterial and fungal community structure, and the abundance of all the N-cycle gene tested, but always in interaction with sampling date. In contrast, nitrapyrin had no significant effect on the emission of VOCs, where only sampling date significantly influenced the profiles observed. Our results point out far-reaching effects of nitrapyrin on soil and plant associated microbial communities, well beyond its predicted direct effect on ammonia-oxidizers. In the longer term, these shifts might counteract the positive effect of nitrapyrin on crop nutrition and greenhouse gas emissions.
Molecular determinants of vascular transport of dexamethasone in COVID-19 therapy
Authors: Shabalin Ivan G. , Czub Mateusz P. , Majorek Karolina A. , Brzezinski Dariusz , Grabowski Marek , Cooper David R. , Panasiuk Mateusz , Chruszcz Maksymilian , Minor Wladek 
Published: July 2020

AbstractDexamethasone, a widely used corticosteroid, has recently been reported as the first drug to increase the survival chances of patients with severe COVID-19. Therapeutic agents, including dexamethasone, are mostly transported through the body by binding to serum albumin. Herein, we report the first structure of serum albumin in complex with dexamethasone. We show that it binds to Drug Site 7, which is also the binding site for commonly used nonsteroidal anti-inflammatory drugs and testosterone, suggesting potentially problematic binding competition. This study bridges structural findings with our analysis of publicly available clinical data from Wuhan and suggests that an adjustment of dexamethasone regimen should be considered for patients affected by two major COVID-19 risk-factors: low albumin levels and diabetes.One Sentence SummaryStructure of serum albumin with dexamethasone reveals why the drug may not always help COVID-19 patients.
Increased isoDGR motifs in plasma fibronectin are associated with atherosclerosis through facilitation of vascular fibrosis
Authors: Park Jung Eun , Guo Xue , Liou Ken Cheng Kang , Lynn Soe EinSi , Ng Ser Sue , Meng Wei , Lim Su Chi , Leow Melvin Khee-Shing , Richards A Mark , Pennington Daniel J , McCarthy Neil E. , de Kleijn Dominique P.V. , Sorokin Vitaly , Ho Hee Hwa , Sze Siu Kwan 
Published: July 2020

AbstractAbnormal matrix deposition on vessels and recruitment of inflammatory cells into the arterial wall are critical events in atherosclerotic plaque formation. Fibronectin protein is a key matrix component that exhibits high levels of deamidation in atherosclerotic plaques and blood plasma, but it is unclear how this structural change impacts on endothelial function or modifies interactions with recruited leukocytes. This study aimed to determine how deamidation-induced isoDGR motifs in fibronectin influence extracellular matrix accumulation on endothelial cells, and to investigate possible effects on integrin ‘outside-in’ signalling in matrix-bound monocytes which are key mediators of human atherosclerosis.Blood plasma fibrinogen and fibronectin displayed marked accumulation of isoDGR motifs in ischemic heart disease (IHD) as determined by ELISA analysis of patients undergoing coronary artery bypass grafting compared with age-matched healthy controls. Biochemical and functional assays confirmed that isoDGR-containing fibronectin promoted activation of integrin β1 in monocytes and facilitated protein deposition and fibrillogenesis on endothelial cell layers. In addition, isoDGR interactions with integrins on the monocyte cell surface triggered an ERK:AP-1 signalling cascade that induced potent secretion of chemotactic mediators (including CCL2, CCL4, IL-8, and TNFα), that promoted further leukocyte recruitment to the assembling plaque.Fibronectin deamidation forms isoDGR motifs that increase binding to β1 integrins on the surface of endothelial cells and monocytes. Subsequent activation of integrin ‘outside-in’ signalling pathways elicits a range of potent cytokines and chemokines that drive additional leukocyte recruitment to the developing atherosclerotic matrix and likely constitutes a key early event in progression to IHD.
Obstructive Sleep Apnea destabilizes myocardial repolarization homogeneity
Authors: Jarecka-Dobroń Aleksandra , Braksator Wojciech , Chrom Paweł 
Published: July 2020

AbstractBackgroundLiterature shows that patients with obesity and Obstructive Sleep Apnea (OSA), both occurring independently, are more likely to develop cardiovascular diseases and sudden cardiac death (SCD). Assuming that ventricular depolarization is more stable than repolarization then QT interval parameters may be used for heart muscle repolarization assessment for those groups of patients.MethodsThere were 121 patients included in the study, both – women and men, aging from 35-65 with visceral obesity. Only healthy patients were included – the ones who were not treated for any chronic disease, taking QT elongating drugs, or were not treated with Continuous Positive Airway Pressure (CPAP) therapy at that time.ResultsOSA was diagnosed in 70 patients (including 41 male). A statistically significant difference for QT interval parameters between OSA positive and negative patients was found (p<0.001 for all variables). No difference for QTc max or for QT interval parameters between groups of patients with different OSA severity degrees was found. A correlation between QTVi2 and QTVi3 (p=0.008) and between polygraphy specific parameters and QTc max, QTVi2 and QTVi3 was found.ConclusionsOSA has a negative influence on heart muscle repolarization processes by increasing QTV and QTVi values, without such an impact on QTc max interval among patients with visceral obesity. A temporary intensification of OSA causes additional increase of QTVi value. OSA severity degree expressed by specific parameters taken from polygraphic examination prolongs QTc max and increases QTV and QTVi values.What is the key question?Does Obstructive Sleep Apnea destabilize heart muscle repolarization time heterogeneity expressed by QT interval assessment parameters (QTc, QTV, QTVi)?What is the bottom line?Obstructive Sleep Apnea occurrence presents an essential negative influence on heart muscle repolarization time, as heterogeneity by QTV and QTVi values increase, while QTc max interval remains unaffected among patients with visceral obesity.Why to read on?Knowing that obesity and Obstructive Sleep Apnea (occurring separately) increase the risk of sudden cardiac death, cardiovascular risk evaluation becomes an important point for obese, OSA positive patient’s care.
Is Kambô psychoactive? Acute and subacute effects of the secretion of the Giant Maki Frog (Phyllomedusa bicolor) on human consciousness
Authors: Schmidt Timo Torsten , Reiche Simon , Hage Caroline L. C. , Bermpohl Felix , Majić Tomislav 
Published: July 2020

ABSTRACTKambô is the name for the secretion of the Giant Leaf Frog (Phyllomedusa bicolor) containing a plethora of bioactive peptides. Originally, it is ritually used by different ethnicities from the Amazon basin as a remedy against bad luck in hunting. In the last twenty years, Kambô has spread to Western urban centers, often associated with the use of ayahuasca. Anecdotal reports claim beneficial effects on wellbeing and different medical and mental health conditions. However, to date it has been controversial if Kambô elicits altered states of consciousness. Here we retrospectively investigated acute and subacute psychological effects of Kambô in a sample of n = 22 anonymous users (n = 22, mean age: 39 years, ± 8.5; 45.5% female), administering standardized questionnaires for the assessment of psychoactive effects. Acutely, participants reported psychological effects which remained on a mild to moderate level, but no psychedelic-type distortions of perception or thinking. In contrast, persisting effects were predominantly described as positive and pleasant, revealing surprisingly high measures of personal and spiritual significance. Subacute and long-term effects showed some overlap with the “afterglow” phenomena that follow the use of serotonergic psychedelics.
Portable real-time colorimetric LAMP-device for rapid quantitative detection of nucleic acids in crude samples
Authors: Papadakis G. , Pantazis A. K. , Fikas N. , Chatziioannidou S. , Tsiakalou V. , Michaelidou K. , Pogka V. , Megariti M. , Vardaki M. , Giarentis K. , Heaney J. , Nastouli E. , Karamitros T. , Mentis A. , Zafiropoulos A. , Sourvinos G. , Agelaki S. , Gizeli E. 
Published: July 2020

AbstractLoop-mediated isothermal amplification is known for its high sensitivity, specificity and tolerance to inhibiting-substances. We developed a device for performing real-time colorimetric LAMP combining the accuracy of lab-based quantitative molecular diagnosis with the simplicity of point-of-care testing. This handheld device employs a single reaction-pot for amplification and a mini-camera for detection. Competitive features are the rapid analysis (<30min), quantification over 9 log-units, crude sample-compatibility (saliva, tissue, swabs), low detection limit (<5copies/reaction), smartphone-operation and fast prototyping (3D-printing). The device’s clinical utility is demonstrated in cancer-mutations and COVID-19 testing. Excellent performance includes: detection of 0.01% ofBRAF-V600E-to-wild-type molecules; 97% sensitivity to SARS-CoV-2 RNA detection (89 samples); 83% (Ct<34), 98% (Ct<30) and 100% (Ct<25) to 163 nasopharyngeal-swabs; 100% specificity in all cases. The device high technology-readiness-level makes it a suitable platform for performing any colorimetric LAMP assay; moreover, its simple and inexpensive fabrication holds promise for fast deployment and application in global diagnostics.
Repeated horizontal gene transfer ofGALactose metabolism genes violates Dollo’s law of irreversible loss
Authors: Haase Max A. B. , Kominek Jacek , Opulente Dana A. , Shen Xing-Xing , LaBella Abigail L. , Zhou Xiaofan , DeVirgilio Jeremy , Hulfachor Amanda Beth , Kurtzman Cletus P. , Rokas Antonis , Hittinger Chris Todd 
Published: July 2020

AbstractDollo’s law posits that evolutionary losses are irreversible, thereby narrowing the potential paths of evolutionary change. While phenotypic reversals to ancestral states have been observed, little is known about their underlying genetic causes. The genomes of budding yeasts have been shaped by extensive reductive evolution, such as reduced genome sizes and the losses of metabolic capabilities. However, the extent and mechanisms of trait reacquisition after gene loss in yeasts have not been thoroughly studied. Here, through phylogenomic analyses, we reconstructed the evolutionary history of the yeast galactose utilization pathway and observed widespread and repeated losses of the ability to utilize galactose, which occurred concurrently with the losses ofGALactose (GAL) utilization genes. Unexpectedly, we detected three galactose-utilizing lineages that were deeply embedded within clades that underwent ancient losses of galactose utilization. We show that at least two, and possibly three, lineages reacquired theGALpathway via yeast-to-yeast horizontal gene transfer. Our results show how trait reacquisition can occur tens of millions of years after an initial loss via horizontal gene transfer from distant relatives. These findings demonstrate that the losses of complex traits and even whole pathways are not always evolutionary dead-ends, highlighting how reversals to ancestral states can occur.
Spatiotemporal dynamics between interictal epileptiform discharges and ripples during associative memory processing
Authors: Henin Simon , Shankar Anita , Borges Helen , Flinker Adeen , Doyle Werner , Friedman Daniel , Devinsky Orrin , Buzsáki György , Liu Anli 
Published: July 2020

ABSTRACTWe describe the spatiotemporal course of cortical high-gamma activity (HGA), hippocampal ripple activity and interictal epileptiform discharges (IEDs) during an associative memory task in 15 epilepsy patients undergoing invasive electroencephalography. Successful encoding trials manifested significantly greater HGA in hippocampus and frontal regions. Successful cued recall trials manifested sustained HGA in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. IEDs during encoding were associated with 15% decreased odds of remembering in hippocampus (95% CI 6-23%). Hippocampal IEDs during retrieval predicted 25% decreased odds of remembering (15-33%). Odds of remembering were reduced by 25-52% if IEDs occurred during the 500-2000 ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal IEDs were followed by a transient decrease in ripple rate. We hypothesize that IEDs impair associative memory in a regionally and temporally specific manner by decreasing physiologic hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological IED events competing with physiological ripples, IEDs represent a promising therapeutic target for memory remediation in patients with epilepsy.SummaryHippocampal interictal epileptiform discharges in hippocampus acutely impair declarative memory, potentially by hijacking physiological processes essential for encoding and recall.
Machine intelligence identifies soluble TNFa as a therapeutic target for spinal cord injury
Authors: Huie JR , Ferguson AR , Kyritsis N , Pan J Z , Irvine K-A , Nielson JL , Schupp PG , Oldham MC , Gensel JC , Lin A , Segal MR , Ratan RR , Bresnahan JC , Beattie MS 
Published: July 2020

SUMMARYTraumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair1,2. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining 5 different blinded, fully counter-balanced treatment trials for different acute anti-inflammatory treatments for cervical spinal cord injury in rats. Multi-dimensional discovery, using topological data analysis3(TDA) and principal components analysis (PCA) revealed that only one showed consistent multidimensional syndromic benefit: intrathecal application of recombinant soluble TNFα receptor 1 (sTNFR1), which showed an inverse-U dose response efficacy. Using the optimal acute dose, we showed that clinically-relevant 90 min delayed treatment profoundly affected multiple biological indices of NI in the first 48 hrs after injury, including reduction in pro-inflammatory cytokines and gene expression of a coherent complex of acute inflammatory mediators and receptors. Further, a 90 min delayed bolus dose of sTNFR1 reduced the expression of NI markers in the chronic perilesional spinal cord, and consistently improved neurological function over 6 weeks post SCI. These results provide validation of a novel strategy for precision preclinical drug discovery that is likely to improve translation in the difficult landscape of CNS trauma, and confirm the importance of TNFα signaling as a therapeutic target.
Beneficial contribution of iPSC-progeny to connexin 47 dynamics during demyelination-remyelination
Authors: Mozafari Sabah , Deboux Cyrille , Laterza Cecilia , Ehrlich Marc , Kuhlmann Tanja , Martino Gianvito , Baron-Van Evercooren Anne 
Published: July 2020

AbstractOligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of CNS myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination-remyelination. Here, we took advantage of LPC-induced demyelination to investigate the expression dynamics of the oligodendrocyte specific connexin 47 (Cx47) and whether this dynamic could be modulated by grafted iPSC-neural progeny. Our data show that deconstruction of the panglial network following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPS-derived oligodendrocytes express Cx47, which co-labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.
Meiotic sister chromatid exchanges are rare inC. elegans
Authors: Almanzar David E. , Gordon Spencer G. , Rog Ofer 
Published: July 2020

AbstractSexual reproduction shuffles the parental genomes to generate new genetic combinations. To achieve that, the genome is subjected to numerous double-strand breaks, the repair of which involves two crucial decisions: repair pathway and repair template. Use of crossover pathways with the homologous chromosome as template exchanges genetic information and directs chromosome segregation. Crossover repair, however, can compromise the integrity of the repair template and is therefore tightly regulated. The extent to which crossover pathways are used during sister-directed repair is unclear, because the identical sister chromatids are difficult to distinguish. Nonetheless, indirect assays have led to the suggestion that inter-sister crossovers, or sister chromatid exchanges (SCEs), are quite common. Here we devised a technique to directly score physiological SCEs in theC. elegansgermline using selective sister chromatid labeling with the thymidine analog 5-ethynyl-2’-deoxyuridine (EdU). Surprisingly, we find SCEs to be rare in meiosis, accounting for <2% of repair events. SCEs remain rare even when the homologous chromosome is unavailable, indicating that almost all sister-directed repair is channeled into noncrossover pathways. We identify two mechanisms that limit SCEs. First, sister-directed repair intermediates are efficiently inhibited by the RecQ helicase BLMHIM-6. Second, the Synaptonemal Complex–a conserved interface that promotes crossover repair– localizes between the homologous chromosomes and not the sister chromatids. Our data suggest that inC. eleganscrossover pathways are only used to generate the single necessary link between the homologous chromosomes. Almost all other breaks, regardless of which repair template they use, are repaired by noncrossover pathways.
Predicting cognitive abilities across individuals using sparse EEG connectivity
Authors: Hakim Nicole , Awh Edward , Vogel Edward K , Rosenberg Monica D 
Published: July 2020

ABSTRACTHuman brains share a broadly similar functional organization with consequential individual variation. This duality in brain function has primarily been observed when using techniques that consider the spatial organization of the brain, such as MRI. Here, we ask whether these common and unique signals of cognition are also present in temporally sensitive, but spatially insensitive, neural signals. To address this question, we compiled EEG data from individuals performing multiple working memory tasks at two different data-collection sites (ns= 171 and 165). Results revealed that EEG connectivity patterns were stable within individuals and unique across individuals. Furthermore, models based on these connectivity patterns generalized across datasets to predict participants’ working memory capacity and general fluid intelligence. Thus, EEG connectivity provides a signature of working memory and fluid intelligence in humans and a new framework for characterizing individual differences in cognitive abilities.