bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serial Profiling of SARS-CoV-2 Antigens and Antibodies in COVID-19 Patient Plasma
Authors: Ogata Alana F. , Maley Adam M. , Wu Connie , Gilboa Tal , Norman Maia , Lazarovits Roey , Mao Chih-Ping , Newton Gail , Chang Matthew , Nguyen Katrina , Kamkaew Maliwan , Zhu Quan , Gibson Travis E. , Ryan Edward T. , Charles Richelle C. , Marasco Wayne A. , Walt David R. 
Published: July 2020

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worldwide. PCR tests are currently the gold standard for diagnosis of the current coronavirus disease (COVID-19) and serology tests are used to detect seroconversion in infected patients. However, there is a lack of quantitative and ultra-sensitive viral antigen tests for COVID-19. Here we show that Single Molecule Array (Simoa) assays can quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of COVID-19 patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we show correlation between production of antibodies and clearance of viral antigens from serial plasma samples from COVID-19 patients. Furthermore, we demonstrate the presence of viral antigens in blood correlates with disease severity in hospitalized COVID-19 patients. These data suggest that SARS-CoV-2 viral antigens in the blood could be a marker for severe COVID-19 cases.One Sentence SummarySARS-CoV-2 antigens S1, spike, and nucleocapsid and anti-SARS-Cov-2 antibodies were measured in longitudinal plasma samples from COVID-19 patients using Single Molecule Array (Simoa) assays.
INDEPENDENT ASSOCIATION OF METEOROLOGICAL CHARACTERISTICS WITH INITIAL SPREAD OF COVID-19 IN INDIA
Authors: Kulkarni Hemant , Khandait Harshwardhan V. , Narlawar Uday W. , Rathod Pragati G. , Mamtani Manju 
Published: July 2020

AbstractWhether weather plays a part in the transmissibility of the novel COronaVIrus Disease-19 (COVID-19) is still not established. We tested the hypothesis that meteorological factors (air temperature, relative humidity, air pressure, wind speed and rainfall) are independently associated with transmissibility of COVID-19 quantified using the basic reproduction rate (R0). We used publicly available datasets on daily COVID-19 case counts (total n = 108,308), three-hourly meteorological data and community mobility data over a three-month period. Estimated R0 varied between 1.15-1.28. Mean daily air temperature (inversely) and wind speed (positively) were significantly associated with time dependent R0, but the contribution of countrywide lockdown to variability in R0 was over three times stronger as compared to that of temperature and wind speed combined. Thus, abating temperatures and easing lockdown may concur with increased transmissibility of COVID-19.
Mild cognitive impairment is associated with skeletal muscle mitochondrial deficits
Authors: Morris Jill K. , McCoin Colin S. , Fuller Kelly N. , John Casey S. , Wilkins Heather M. , Wang Xiaowan , Sharma Palash , Burns Jeffrey M. , Vidoni Eric D. , Mahnken Jonathan D. , Swerdlow Russell H. , Thyfault John P. 
Published: July 2020

AbstractAlzheimer’s Disease (AD) is associated with insulin resistance and low cardiorespiratory fitness, suggestive of impaired skeletal muscle mitochondrial function. We examined if individuals with Mild Cognitive Impairment (MCI), the earliest phase of AD-related cognitive decline, exhibit reduced skeletal muscle mitochondrial function, and if AD medication impacted outcomes. We present data from 50 individuals, including cognitively healthy older adults (CH; n=24) 60+ years of age and clinically diagnosed MCI subjects (n=26). MCI subjects were sub-divided into two groups; no AD medication (MCI; n=11), or AD medication treated (MCI+med; n=15). A skeletal muscle biopsy (vastus lateralis) was obtained and mitochondrial respiratory kinetics was measured in permeabilized muscle fibers. MCI subjects exhibited lower lipid-stimulated skeletal muscle mitochondrial respiration (State 3, ADP-stimulated) than both CH individuals (p=0.043) and medication-treated MCI subjects (p=0.006). MCI also exhibited poorer mitochondrial coupling control compared to CH subjects (p=0.014), while MCI+med and CH subjects did not differ. Compared to CH individuals, skeletal muscle mitochondrial leak control ratio was lower for the MCI+med group (p=0.008) and trended lower for non-medicated MCI (p=0.06), which suggests greater mitochondrial uncoupling in MCI. Skeletal muscle mitochondrial respiration is impaired in untreated MCI but normalized in medication-treated MCI participants while mitochondrial leak control is impaired regardless of medication status. These results provide further evidence that systemic mitochondrial deficits occur in the very early stages of AD, and that mitochondrial function is partially influenced by AD medication. Further analysis for a role of muscle mitochondria in the progression of early AD is warranted.
Viral RNA level, serum antibody responses, and transmission risk in discharged COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study
Authors: Yang Chao , Jiang Min , Wang Xiaohui , Tang Xiujuan , Fang Shisong , Li Hao , Zuo Le , Jiang Yixiang , Zhong Yifan , Chen Qiongcheng , Zheng Chenli , Wang Lei , Wu Shuang , Wu Weihua , Liu Hui , Yuan Jing , Liao Xuejiao , Zhang Zhen , Lin Yiman , Geng Yijie , Zhang Huan , Zheng Huanying , Wan Min , Lu Linying , Ren Xiaohu , Cui Yujun , Zou Xuan , Feng Tiejian , Xia Junjie , Yang Ruifu , Liu Yingxia , Mei Shujiang , Li Baisheng , Yang Zhengrong , Hu Qinghua 
Published: July 2020

SummaryBackgroundManaging discharged COVID-19 (DC) patients with recurrent positive (RP) SARS-CoV-2 RNA test results is challenging. We aimed to comprehensively characterize the viral RNA level and serum antibody responses in RP-DC patients and evaluate their viral transmission risk.MethodsA population-based observational cohort study was performed on 479 DC patients discharged from February 1 to May 5, 2020 in Shenzhen, China. We conducted RT-qPCR, antibody assays, neutralisation assays, virus isolation, whole genome sequencing (WGS), and epidemiological investigation of close contacts.FindingsOf 479 DC patients, the 93 (19%) RP individuals, including 36 with multiple RP results, were characterised by young age (median age: 34 years, 95% confidence interval [CI]: 29–38 years). The median discharge-to-RP length was 8 days (95% CI: 7–14 days; maximum: 90 days). After readmission, RP-DC patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in RP-DC patients ranged from 1·9–5·7 log10copies/mL (median: 3·2, 95% CI: 3·1–3·5). At RP detection, the IgM, IgG, IgA, total antibody, and neutralising antibody (NAb) seropositivity rates in RP-DC patients were 38% (18/48), 98% (47/48), 63% (30/48), 100% (48/48), and 91% (39/43), respectively. Regarding antibody levels, there was no significant difference between RP-DC and non-RP-DC patients. The antibody level remained constant in RP-DC patients pre- and post-RP detection. Virus isolation of nine representative specimens returned negative results. WGS of six specimens yielded only genomic fragments. No clinical symptoms were exhibited by 96 close contacts of 23 RP-DC patients; their viral RNA (96/96) and antibody (20/20) test results were negative. After full recovery, 60% of patients (n=162, 78 no longer RP RP-DC and 84 non-RP-DC) had NAb titres of ≥1:32.InterpretationRP may occur in DC patients following intermittent and non-stable excretion of low viral RNA levels. RP-DC patients pose a low risk of transmitting SARS-CoV-2. An NAb titre of ≥ 1:32 may provide a reference indicator for evaluating humoral responses in COVID-19 vaccine clinical trials.FundingSanming Project of Medicine in Shenzhen, China National Science and Technology Major Projects Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province of China, and Shenzhen Committee of Scientific and Technical Innovation grants.
Biophysical and dynamic characterization of a fine-tuned binding of the human Respiratory Syncytial Virus M2-1 core domain to long RNAs
Authors: Caruso Icaro P. , Guimarães Giovana C. , Machado Vitor B. , Fossey Marcelo A. , Willbold Dieter , Almeida Fabio C. L. , Souza Fátima P. 
Published: July 2020

ABSTRACTThe human Respiratory Syncytial Virus (hRSV) M2-1 protein functions as a processivity and antitermination factor of the viral polymerase complex. Here it is presented the first evidence that hRSV M2-1 core domain (cdM2-1) alone has an unfolding activity for long RNAs, as well as a biophysical and dynamic characterization of the cdM2-1/RNA complex. The main contact region of cdM2-1 with RNA was the α1–α2–α5–α6 helix bundle, which suffered local conformational changes and promoted the RNA unfolding activity. This activity may be triggered by base-pairing recognition. RNA molecules wrap around the whole cdM2-1, protruding their terminals over the domain. The α2–α3 and α3–α4 loops of cdM2-1 were marked by an increase in picosecond internal motions upon RNA binding even though they are not directly involved in the interaction. The results revealed that the cdM2-1/RNA complex originates from a fine-tuned binding, contributing to unraveling interaction aspects necessary to M2-1 activity.IMPORTANCEThe main outcome is the molecular description of a fine-tuned binding of the cdM2-1/RNA complex and the evidence that the domain alone has an unfolding activity for long RNAs. This binding mode is essential in the understanding of the function in the full-length protein. Orthopneumovirus, as the human Respiratory Syncytial Virus (hRSV), stands out for the unique role of M2-1 as a transcriptional antitermination factor able to increase the RNA polymerase processivity.
TRANsCre-DIONE transdifferentiates scar-forming reactive astrocytes into functional motor neurons
Authors: An Heeyoung , Lee Hye-Lan , Cho Doo-Wan , Hong Jinpyo , Lee Hye Yeong , Lee Jung Moo , Woo Junsung , Lee Jaekwang , Park MinGu , Yang Young-Su , Han Su-Cheol , Ha Yoon , Lee C. Justin 
Published: July 2020

SUMMARYIn spinal cord injury (SCI), the scar-forming reactive astrocytes with upregulated GFAP proliferate aberrantly near the injury site, allowing themselves as a prime target for transdifferentiation into neurons to replenish dead neurons. However, the conventional use ofGFAPpromoter to target reactive astrocytes has two inherent problems: inadvertent conversion of normal astrocytes and low efficiency due to progressive weakening of promoter activity during transdifferentiation. Here, we report that the scar-forming reactive astrocytes are selectively transdifferentiated into neurons with 87% efficiency and 96% specificity via TRANsCre-DIONE, a combination of the split-Cre system under two different promoters ofGFAPandLcn2and a Cre-loxP-dependent inversion and expression ofNeurog2under the strongEF1αpromoter. After SCI, TRANsCre-DIONE caused transdifferentiation into Isl1-positive motor neurons, reduced astrogliosis, enhanced regeneration in surrounding cells, and a significant motor recovery. Our study proposes TRANsCre-DIONE as the next-generation therapeutic approach for patients suffering from SCI.HighlightsTRANsCre-DIONE converts reactive astrocyte into neuron by over-expression ofNeurog2Reactive astrocytes are targeted using split-Cre under two promoters,GFAPandLcn2TRANsCre-DIONE reduces reactivity, replaces dead neurons and alleviates symptom of SCI Transdifferentiated-neurons are GABA+ in the striatum and Isl1+ in the spinal cord
Host genotype and stable differences in algal symbiont communities explain patterns of thermal stress response ofMontipora capitatafollowing thermal pre-exposure and across multiple bleaching events
Authors: Dilworth Jenna , Caruso Carlo , Kahkejian Valerie A. , Baker Andrew C. , Drury Crawford 
Published: July 2020

AbstractAs sea surface temperatures increase worldwide due to climate change, coral bleaching events are becoming more frequent and severe, resulting in reef degradation. Leveraging the inherent ability of reef-building corals to acclimatize to thermal stress via pre-exposure to protective temperature treatments may become an important tool in improving the resilience of coral reefs to rapid environmental change. We investigated whether historical bleaching phenotype, coral host genotype, and exposure to protective temperature treatments would affect the response of the Hawaiian coralMontipora capitatato natural thermal stress. Fragments were collected from colonies that demonstrated different bleaching responses during the 2014-2015 event in Kāne’ohe Bay (O’ahu, Hawai’i) and exposed to four different artificial temperature pre-treatments (and a control at ambient temperature). After recovery, fragments experienced a natural thermal stress event either in laboratory conditions or their native reef environment. Response to thermal stress was quantified by measuring changes in the algal symbionts’ photochemical efficiency, community composition, and relative density. Historical bleaching phenotype was reflected in stable differences in symbiont community composition, with historically bleached corals containing onlyCladocopiumsymbionts and historically non-bleached corals having mixed symbiont communities dominated byDurusdinium. Mixed-community corals lost moreCladocopiumthanCladocopium-only corals during the natural thermal stress event, and preferentially recovered withDurusdinium. Laboratory pre-treatments exposed corals to more thermal stress than anticipated, causing photochemical damage that varied significantly by genotype. While none of the treatments had a protective effect, temperature variation during treatments had a significant detrimental effect on photochemical efficiency during the thermal stress event. These results show that acclimatization potential is affected by fine-scale differences in temperature regime, host genotype, and relatively stable differences in symbiont community composition that underpin historical bleaching phenotypes inM. capitata.
In-SilicoAnalysis of Secondary Metabolites that Modulates Enzymes of Cholesterol Target
Authors: Marahatha Rishab , Basnet Saroj , Bhattarai Bibek Raj , Budhathoki Prakriti , Aryal Babita , Adhikari Bikash , Lamichhane Ganesh , Poudel Darbin Kumar , Parajuli Niranjan 
Published: July 2020

AbstractHypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generates atherosclerosis and cholesterol crystals. β-Hydroxy β-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced the cholesterol level, most of them have failed to meet the requirements of being apt drug candidates. Here, we have carried out anin-silicoanalysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR. Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were taken based on IC50values reportedin vitroassays. Further, receptor-based virtual screening was carried out against secondary metabolites usingGOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-SilicoADMET analysis was carried out to study their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. The molecular docking of amentoflavone(1)(GOLD score 70.54), and ganomycin I(9)(GOLD score 59.61) evinced that the drug has effectively bind at the competitive site of XO and HMGR, respectively. Besides, 6-paradol(3)and selgin(4)could be potential drug candidates to inhibit XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl(6’→1”)-O-α-D-glucopyranoside(10)could be potential drug candidates to maintain serum cholesterol.In-silicoADMET analysis showed that the sixteen metabolites were optimal within the categorical range in comparison to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through Protox-II revealed that 6-gingerol(2), ganoleucoin K(11), and ganoleucoin Z(12)are toxic for human use. This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.Graphical abstract
Hijacking of the host cell Golgi byPlasmodiumliver stage parasites
Authors: De Niz Mariana , Kaiser Gesine , Zuber Benoit , Do Heo Won , Heussler Volker T. , Agop-Nersesian Carolina 
Published: July 2020

AbstractThe intracellular lifestyle represents a challenge for the rapidly proliferating liver stagePlasmodiumparasite. In order to scavenge host resources,Plasmodiumhas evolved the ability to target and manipulate host cell organelles. Using dynamic fluorescence-based imaging, we show a direct interplay between the pre-erythrocytic stages ofPlasmodium bergheiand the host cell Golgi during the entire liver stage development. Liver stage schizonts fragment the host cell Golgi into miniaturized stacks, which increases surface interactions with the parasite’s parasitophorous vacuole membrane. Interference with the host cell Golgi-linked vesicular machinery using specific dominant-negative Arf and Rab GTPases results in developmental arrest and diminished survival of liver stage parasites. Moreover, functional Rab11a is critical for the parasites ability to induce Golgi fragmentation. Altogether, we demonstrate that the structural and functional integrity of the host cell Golgi is necessary for optimal pre-erythrocytic development ofP. berghei. The parasite hijacks the hepatocyte’s Golgi structure to optimize its own intracellular development.
LIN-10 can promote LET-23 EGFR signaling and trafficking independently of LIN-2 and LIN-7
Authors: Gauthier Kimberley D. , Rocheleau Christian E. 
Published: July 2020

AbstractDuringC. eleganslarval development, an inductive signal mediated by LET-23 EGFR (Epidermal Growth Factor Receptor) specifies three of six vulva precursor cells (VPCs) to adopt vulval cell fates. An evolutionarily conserved complex consisting of PDZ domain-containing scaffold proteins LIN-2 (CASK), LIN-7 (Lin7 or Veli), and LIN-10 (APBA1 or Mint1) (LIN-2/7/10) mediates basolateral LET-23 EGFR localization in the VPCs to permit signal transmission and development of the vulva. We recently found that the LIN-2/7/10 complex likely forms at Golgi ministacks or recycling endosomes; however, the mechanism through which the complex targets the receptor to the basolateral membrane remains unknown. Here we found that overexpression of LIN-10 or LIN-7 can compensate for loss of their complex components by promoting LET-23 EGFR signaling through previously unknown complex-independent and receptor-dependent pathways. In particular, LIN-10 can independently promote basolateral LET-23 EGFR localization, and its complex-independent function uniquely requires its PDZ domains that also regulate its localization to Golgi ministacks and recycling endosomes. These studies point to a novel complex-independent function for LIN-7 and LIN-10 that broadens our understanding of how this complex regulates targeted sorting of membrane proteins.
Electrophysiological foundations of the human default-mode network revealed by brain-wide intracranial-EEG recordings during resting-state and cognition
Authors: Das Anup , de los Angeles Carlo , Menon Vinod 
Published: July 2020

AbstractInvestigations using noninvasive functional magnetic resonance imaging (fMRI) have provided significant insights into the unique functional organization and profound importance of the human default mode network (DMN), yet these methods are limited in their ability to resolve network dynamics across multiple timescales. Electrophysiological techniques are critical to address these challenges, yet few studies have explored the neurophysiological underpinnings of the DMN. Here we investigate the brain-wide electrophysiological organization of the DMN in a common large-scale network framework consistent with prior fMRI studies. We used brain-wide intracranial EEG (iEEG) recordings, and evaluated intra- and cross-network interactions during the resting-state and cognition. Our analysis revealed significantly greater intra-DMN phase iEEG synchronization in the slow-wave (< 4 Hz) while DMN interactions with other brain networks was higher in all higher frequencies. Crucially, slow-wave intra-DMN synchronization was observed in the task-free resting-state and during verbal memory encoding and recall. Compared to resting-state, intra-DMN phase synchronization was significantly higher during both memory encoding and recall. Slow-wave intra-DMN phase synchronization increased during successful memory retrieval, highlighting its behavioral relevance. Finally, analysis of nonlinear dynamic causal interactions revealed that the DMN is a causal outflow network during both memory encoding and recall. Our findings identify dynamic spectro-temporal network features that allow the DMN to maintain a balance between stability and flexibility, intrinsically and during task-based cognition, provide novel insights into the neurophysiological foundations of the human DMN, and elucidate network mechanisms by which it supports cognition.
Genome-wide variation in DNA methylation linked to developmental stage and chromosomal suppression of recombination in white-throated sparrows
Authors: Sun Dan , Layman Thomas S. , Jeong Hyeonsoo , Chatterjee Paramita , Grogan Kathleen , Merritt Jennifer , Maney Donna L. , Yi Soojin V. 
Published: July 2020

ABSTRACTDNA methylation is known to play critical roles in key biological processes. Most of our knowledge on regulatory impacts of DNA methylation has come from laboratory-bred model organisms, which may not exhibit the full extent of variation found in wild populations. Here, we investigated naturally-occurring variation in DNA methylation in a wild avian species, the white-throated sparrow (Zonotrichia albicollis). This species offers exceptional opportunities for studying the link between genetic differentiation and phenotypic traits because of a non-recombining chromosome pair linked to both plumage and behavioral phenotypes. Using novel single-nucleotide resolution methylation maps and gene expression data, we show that DNA methylation and the expression of DNA methyltransferases are significantly higher in adults than in nestlings. Genes for which DNA methylation varied between nestlings and adults were implicated in development and cell differentiation and were located throughout the genome. In contrast, differential methylation between plumage morphs was localized to the non-recombining chromosome pair. One subset of CpGs on the non-recombining chromosome was extremely hypomethylated and localized to transposable elements. Changes in methylation predicted changes in gene expression for both chromosomes. In summary, we demonstrate changes in genome-wide DNA methylation that are associated with development and with specific functional categories of genes in white-throated sparrows. Moreover, we observe substantial DNA methylation reprogramming associated with the suppression of recombination, with implications for genome integrity and gene expression divergence. These results offer an unprecedented view of ongoing epigenetic reprogramming in a wild population.