bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying and characterizing a novel Sindbis virus capsid and IRAK1 interaction
Authors: Landers V , Sokoloski Kevin 
Published: July 2020

Alphaviruses are arthropod-borne positive-sense RNA viruses that have the capacity to cause large scale outbreaks of severe disease. As of now, there are no effective therapeutic strategies with which alphaviral disease may be treated. Thus, there is a need for research that defines the mechanism(s) by which the alphaviruses establish infection and cause pathogenesis. Our previous work identified non-assembly interactions between the SINV Capsid protein and the viral genomic RNA that were important for viral RNA stabilization early during infection. These efforts led us to evaluate the Protein:Protein interactions of the SINV Capsid protein using the BioID2 discovery approach to define the mechanism of action underlying the SINV Capsid-mediated genome stability.
To our surprise, these efforts indicated that the SINV CP protein interacts with the host IRAK1 protein in tissue culture models of infection. To validate the interface we utilized a Bimolecular Fluorescence Complementation approach to confirm the SINV Capsid-IRAK1 interaction. After confirming the novel Capsid Protein:Protein interaction we hypothesized that the SINV Capsid protein may interfere with IRAK1-dependent signaling during infection. To this end, we assessed the dose-responsiveness of several IRAK1-dependent signaling pathways, including TLRs 4 and 7 in the presence of the SINV Capsid protein. We found that the TLR-agonist response, was significantly decreased in the presence of the SINV Capsid protein. Collectively, these data are highly suggestive that the SINV Capsid protein interferes with TLR signaling during viral infection contributing to the evasion of the host innate immune response.
How environment shapes horizontal gene transfer
Authors: Bhatia Rama , Kirit Hande , Bollback Jonathan 
Published: July 2020

The evolutionary fate of a horizontal gene transfer (HGT) event is determined by its fitness on the recipient cell, i.e., whether it is beneficial, neutral or deleterious. The distribution of fitness effects (DFE), thus is a fundamental predictor of the outcome of an HGT event.
The environment plays a considerable role in determining the fitness cost of a horizontally transferred gene. We have studied the fitness effects of genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli in six environments, that potentially represent the conditions experienced by the two species. The data suggests high variability of genes in different environments. Genes, whose fitness varies substantially between environments, may be able to persist in populations while being deleterious in one environment, they may be neutral or even beneficial in another environment, suggesting that environmental fluctuations may increase the likelihood of HGT.
In addition to the in vitro environments, we are also looking at, how changes in the intrinsic environment of a cell, after an HGT event, could affect fitness. An increase in protein dosage due to functional similarity of the horizontally transferred gene to the endogenous gene can cause an imbalance in the cell, thereby leading to a negative fitness effect. By comparing the growth rates of each ortholog gene with the wild type strain, we can elucidate when gene dosage acts as a barrier to HGT.
Synthrophic interactions between Bacteroides and Bifidobacterium on yeast beta-glucan
Authors: Fernandez-Julia Pedro , Munoz Jose 
Published: July 2020

The Human Gut Microbiota (HGM) comprises two major phyla, the Bacteroidetes and Firmicutes, although important members of the Actinobacteria (Bifidobacterium) and Verrucomicrobia (Akkemansia) also make an important contribution to this ecosystem.
Accumulating datasupport the notionthat the HGM can be modulated by probiotics and prebiotics to prevent or revert common diseases of the gastrointestinal tract (GIT) such as Inflammatory Bowel Disease. Because it is believed that these GIT diseases are linked to the fact that current Western populations follow a more fat-based diet, significant efforts have been made to search for novel prebiotics/probiotics in order to restore and improve gut health.
So far, no publications have described probiotic properties of Bacteroidetes. Nonetheless, a case can be made that certain Bacteroides species present primary glycan degraders that interact in a syntrophic manner with other members of the microbiota, such as bifidobacteria, which are considered beneficial members of the microbiota.
In this study, we present the simbiotic interactions between Bacteroides and Bifidobacterium spp. acting on yeast beta-glucan (1,3/1,6 mixed linkage beta-glucan). Bacteroides cellulosilyticus and Bacteroides ovatus act as keystone organism to share beta-1,3/1,6-glucooligosaccharides with other members of the HGM, including Bifidobacterium breve UCC2003 and Bifidobacterium bifidum. We show in these Bifidobacterium spp. a specific beta-1,3-glucosidase, which degrade some of these sharing oligosaccharides. Also, we have identified the specific sugar symporter, which incorporate these oligosaccharides into the cytoplasm of B. breve UCC2003. With the help of RT-qPCR, we have quantified and monitored how these two members of the HGM are able to symbioticly use this dietary glycan.
Spectral analysis of the daily evolution of deaths due to Covid-19 in France and in the world shows a weekend effect: myth or reality?
Authors: Constantinesco André , Israel-Jost Vincent , Choquet Philippe 
Published: July 2020

ABSTRACTBackgroundThe weekend effect has been extensively observed for different diseases and countries and recognized as a fact but without obvious causes.ObjectivesIn this paper we first aimed at investigating the existence of a periodicity in the death count due to Covid-19, and second, at opening the discussion concerning the reality of this effect in this particular context.MethodsDaily statistics of deaths due to the Covid-19 pandemic were subjected to a discrete Fourier transform spectral analysis for France and the world, over the periods from March 29 to May 16, 2020 and from January 22 to May 18, 2020 respectively.ResultsIn both cases, a frequency peak of one harmonic corresponding to a period of 7.11 days was observed for France and the world. In France, this weekly frequency corresponds to a decrease in deaths every Sunday, whereas for the world the systematic decrease is shifted on average by 1.5 days and corresponds to Saturday or Friday.ConclusionAt the world scale and for the epidemic period we confirm the existence of a consecutive weekend effect in the context of the Covid-19 pandemic.
Clinical and epidemiological characteristics of children with SARS-CoV-2 infection: case series in Sinaloa
Authors: Pérez Gaxiola Giordano , Rocha Rosalino Flores , Valadez Vidarte Julio César , Alcaraz Melissa Hernández , Mendoza Gilberto Herrera , Del Real Lugo Miguel Alejandro 
Published: July 2020

AbstractBackgroundThe SARS-CoV-2 virus may affect both adults and children. Although the disease, named COVID-19, has a lower prevalence in infancy and has been described as mild, the clinical characteristics may vary and there is a possibility of complications.ObjectivesTo describe the clinical and epidemiological characteristics of pediatric cases confirmed in the state of Sinaloa, Mexico, during the first three months of the pandemic, and of children admitted with COVID-19 to a secondary hospital.MethodsThis case series includes all patients with SARS-CoV-2 infection confirmed by PCR testing, identified in the state epidemiological surveillance system between March 1 and May 31, 2020. Confirmed patients admitted to the Sinaloa Pediatric Hospital (HPS) during the same dates are also described.ResultsFifty one children with SARS-CoV-2 were included, 10 of the admitted to HPS. The median age was 10 years. The more frequent symptoms were fever (78%), cough (67%) and headache (57%). Most cases were mild or asymptomatic. Three patients with comorbidities died. Only 4 of 10 patients identified in HPS had been admitted with the diagnosis of possible COVID-19.ConclusionsSARS-CoV-2 infection in children was mostly mild or asymptomatic, but with a wide range of clinical presentations.
Creating Red Light-Controlled Protein Dimerization Systems as Genetically Encoded Actuators with High Specificity
Authors: Huang Zhimin , Li Zengpeng , Zhang Xiao , Dong Runze , Kang Shoukai , Sun Li , Fu Xiaonan , Vaisar David , Watanabe Kurumi , Gu Liangcai 
Published: July 2020

AbstractProtein dimerization systems that can be controlled by red light with increased tissue penetration depth are a highly needed optogenetic tool for clinical applications such as cell and gene therapies. However, existing red light-induced dimerization systems are all based on phytochrome photoreceptors and naturally occurring binding partners with complex structures and suboptimalin vivoperformance, limiting mammalian applications. Here, we introduce an efficient, generalizable method (COMBINES-LID) for creating highly specific light-induced dimerization systems. Proof-of-principle was provided by creatingnanobody-based,red light-induceddimerization (nanoReD) systems comprising a truncated bacterial phytochrome sensory module using a mammalian endogenous chromophore, biliverdin, and light-form specific nanobodies. Selected nanoReD systems were biochemically characterized and exhibited low dark activity and high induction specificity forin vivoactivation of gene expression. Overall, COMBINES-LID opens new opportunities for creating genetically encoded actuators for the optical manipulation of biological processes.
Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection
Authors: Seow Jeffrey , Graham Carl , Merrick Blair , Acors Sam , Steel Kathyrn J.A. , Hemmings Oliver , O’Bryne Aoife , Kouphou Neophytos , Pickering Suzanne , Galao Rui Pedro , Betancor Gilberto , Wilson Harry D. , Signell Adrian W. , Winstone Helena , Kerridge Claire , Temperton Nigel , Snell Luke , Bisnauthsing Karen , Moore Amelia , Green Adrian , Martinez Lauren , Stokes Brielle , Honey Johanna , Izquierdo-Barras Alba , Arbane Gill , Patel Amita , O’Connell Lorcan , O’Hara Geraldine , MacMahon Eithne , Douthwaite Sam , Nebbia Gaia , Batra Rahul , Martinez-Nunez Rocio , Edgeworth Jonathan D. , Neil Stuart J.D. , Malim Michael H. , Doores Katie J 
Published: July 2020

AbstractAntibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy’s and St Thomas’ Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.
Genome-wide association study in 8,956 German individuals identifies influence of ABO histo-blood groups on gut microbiome
Authors: Rühlemann Malte Christoph , Hermes Britt Marie , Bang Corinna , Doms Shauni , Moitinho-Silva Lucas , Thingholm Louise Bruun , Frost Fabian , Degenhardt Frauke , Wittig Michael , Kässens Jan , Weiss Frank Ulrich , Peters Annette , Neuhaus Klaus , Völker Uwe , Völzke Henry , Homuth Georg , Weiss Stefan , Laudes Matthias , Lieb Wolfgang , Haller Dirk , Lerch Markus M. , Baines John F. , Franke Andre 
Published: July 2020

AbstractThe intestinal microbiome is implicated as an important modulating factor in multiple inflammatory,1,2 neurologic,3 and neoplastic diseases.4 Recent genome-wide association studies yielded inconsistent, underpowered and rarely replicated results such that the role of human host genetics as a contributing factor to microbiome assembly and structure remains uncertain.5–11 Nevertheless, twin-studies clearly suggest host-genetics as driver of microbiome composition.11 In a genome-wide association analysis of 8,956 German individuals, we identified 32 genetic loci to be associated with single bacteria and overall microbiome composition. Further analyses confirm the identified associations of ABO histo-blood groups and FUT2 secretor status with Bacteroides and Faecalibacterium. Mendelian randomization analysis suggests causative and protective effects of gut microbes, with clade-specific effects on inflammatory bowel disease. This holistic investigative approach of the host, its genetics, and its associated microbial communities as a ‘metaorganism’ broadens our understanding of disease aetiology and emphasizes the potential for implementing microbiota in disease treatment and management.
Non contrast-enhanced imaging as a replacement for contrast-enhanced imaging for MRI automatic delineation of nasopharyngeal carcinoma
Authors: Wong Lun M. , Ai Qi-yong H. , Mo Frankie K.F. , Poon Darren M.C. , King Ann D. 
Published: July 2020

AbstractConvolutional neural networks (CNNs) show potential for delineating cancers on contrast-enhanced MRI. However, there is world-wide interest in reducing the administration of MRI contrast agents. We aim to determine if CNNs can automatically delineate primary nasopharyngeal carcinoma (NPC) using the non contrast-enhanced (NE) T2-weighted fat-suppressed T1-weighted (CE-T1W) sequence. We retrospectively analyzed primary tumors in 201 patients with NPC. Six patients were randomly sampled as the training-validation group to avoid over-fitting, and the remaining 195 patients underwent validation analysis. We trained and tested a well-established two-dimensional CNN, U-Net, for tumor delineation on CE-T1W and T2W-FS sequences. CNN-derived delineations on CE-T1W and T2W-FS were compared with manual delineation using the dice similarity coefficient (DSC) and average surface distance (ASD). Differences in DSC and ASD of CNN-derived delineations between CE-T1W and T2W-FS sequences were compared using the Wilcoxon rank test. CNN-derived primary tumor volumes (PTVs) on CE-T1W and T2W-FS were also compared with manual delineation using the Wilcoxon rank test. The CNN’s tumor delineation performance on CE-T1W and T2W-FS showed no differences in DSC (0.71±0.09 vs. 0.71±0.09, p=0.50) and ASD (0.21±0.48cm vs. 0.17±0.19cm, p=0.34). The CNN-derived PTVs were larger than those from manual delineation on both CE-T1W (26.3±25.5cm3 vs. 23.5±26.6cm3, p<0.001) and T2W-FS (24.2±23.7cm3 vs. 23.2 ± 26.2 cm3, p<0.001). In conclusion, CNN can automatically delineate primary NPC using the NE T2W-FS sequence which has the potential to be a substitute for the CE-T1W sequence. (T2W-FS) sequence and compare the performance with that from the contrast-enhanced
In vivodemonstration of microvascular thrombosis in severe Covid-19
Authors: do Espírito Santo Douglas Alexandre , Lemos Anna Cristina Bertoldi , Miranda Carlos Henrique 
Published: July 2020

AbstractSeveral autopsies studies showed the presence of microthrombi in the pulmonary circulation of the severe COVID-19. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation (DIC) observed as the final common pathway of the multisystem organ failure exhibited in the critical patient. We report the preliminary results of an invivoevaluation of the sublingual microcirculation in thirteen patients with severe COVID-19 requiring mechanical ventilation at the beginning of the hospitalization. They did not have any laboratorial DIC evidence. We observed multiple filling defects moving within the sublingual microvessels indicative of microthrombi in 11 (85%) patients. This is the first imaging documentation of microvascular thrombosis in living patients with severe COVID-19. The clinical relevance of microvascular thrombosis in this disease requires further research.HighlightsThe presence of microthrombi in the pulmonary circulation is a common finding in autopsies of severe COVID-19.In vivo evaluation of the sublingual microcirculation of severe COVID-19 showed multiple filling defects moving within the microvessels indicative of thrombi in most of these patients.This is the first imaging documentation of microvascular thrombosis in living patients with severe COVID-19.The clinical relevance of microvascular thrombosis in COVID-19 requires further research.
Entrainment of network activity by closed-loop microstimulation in healthy ambulatory rats
Authors: Averna Alberto , Hayley Page , Murphy Maxwell D , Nguyen Jimmy , Buccelli Stefano , Barban Federico , Nudo Randolph J. , Chiappalone Michela , Guggenmos David J. 
Published: July 2020

AbstractAs our understanding of how motor output is generated increases, it is clear that there is a need to understand the interactions of multiple distinct regions rather than just the output properties of primary motor cortex. This becomes even more imperative when trying to understand how different regions may contribute to recovery following injury. In this study we used a technique that promotes functional motor recovery after injury, activity-dependent stimulation (ADS), to determine the short- and long-term effects on network activity and neuroplasticity of intracortical connections. ADS uses recorded neural activity to trigger stimulation of the brain and may be utilized to manipulate neuronal connectivityin vivo, representing a novel technique to shape intrinsic neuroplasticity. The aim of this work was to compare the effect of ADS to randomly-generated stimulation (RS) of the somatosensory area (S1) on the single units’ patterns of activity taking place in the premotor cortex (RFA) and to investigate whether synaptic plasticity changes occur in S1 as a consequence of 21 consecutive days of stimulation. In particular, we examined both firing rate changes and correlation between spiking activity and stimuli in chronically-implanted healthy ambulatory rats during both spontaneous and evoked activity, resulting from the two stimulation paradigms. Finally, we evaluated changes in expression of synaptophysin at the end of the treatment. This experimental procedure demonstrated the ability of ADS to modulate firing properties of RFA within daily recording sessions and to promote synaptogenesis in S1, further strengthening the idea that this Hebbian-inspired protocol can be used to effectively modulate cortical connectivity and thus suggesting its translational potential for promoting recovery after brain injury.
Modelling cell guidance and curvature control in evolving biological tissues
Authors: Hegarty-Cremer Solene G.D. , Simpson Matthew J. , Andersen Thomas L. , Buenzli Pascal R. 
Published: July 2020

AbstractTissue geometry is an important influence on the evolution of many biological tissues. The local curvature of an evolving tissue induces tissue crowding or spreading, which leads to differential tissue growth rates, and to changes in cellular tension, which can influence cell behaviour. Here, we investigate how directed cell motion interacts with curvature control in evolving biological tissues. Directed cell motion is involved in the generation of angled tissue growth and anisotropic tissue material properties, such as tissue fibre orientation. We develop a new cell-based mathematical model of tissue growth that includes both curvature control and cell guidance mechanisms to investigate their interplay. The model is based on conservation principles applied to the density of tissue synthesising cells at or near the tissue’s moving boundary. The resulting mathematical model is a partial differential equation for cell density on a moving boundary, which is solved numerically using a hybrid front-tracking method called the cell-based particle method. The inclusion of directed cell motion allows us to model new types of biological growth, where tangential cell motion is important for the evolution of the interface, or for the generation of anisotropic tissue properties. We illustrate such situations by applying the model to simulate both the resorption and infilling components of the bone remodelling process, and to simulate root hair growth. We also provide user-friendly MATLAB code to implement the algorithms.
Structure-informed functional connectivity driven by identifiable and state-specific control regions
Authors: Chiêm Benjamin , Crevecoeur Frédéric , Delvenne Jean-Charles 
Published: July 2020

AbstractA challenge in neuroscience is to describe the contribution of the brain anatomical wiring to the emergence of coordinated neural activity underlying complex behavior. Indeed, patterns of remote coactivations that adjust with the ongoing task-demand do not systematically match direct, static anatomical links. Here, we propose that observed coactivation patterns, known as Functional Connectivity (FC), can be explained by a linear diffusion dynamics defined on the brain architecture and driven by control regions. Our model, termedstructure-informedFC, is based on a novel interpretation of functional connectivity according to which different sets of brain regions controlling the information flow on a fixed anatomical wiring enable the emergence of state-specific FC. This observation leads us to introduce a framework for the identification of potential control centers in the brain. We find that well-defined, sparse and robust sets of control regions, which partially overlap across several task conditions and resting-state, produce FC patterns comparable to empirical ones. In conclusion, this work introduces a principled method for identifying brain regions underlying the task-specific control of brain activity.Significance statementUnderstanding how brain anatomy promotes particular patterns of coactivations among neural regions is a key challenge in neuroscience. This challenge can be addressed using network science and systems theory. Here, we propose that coactivations result from the diffusion of information through the network of anatomical links connecting brain regions, with certain regions controlling the dynamics. We translate this hypothesis into a model calledstructure-informed functional connectivity, and we introduce a framework for identifying control regions based on empirical data. We find that our model produces coactivation patterns comparable to empirical ones, and that distinct sets of control regions are associated with different functional states. These findings suggest that controllability is an important feature allowing the brain to reach different states.