bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung biopsy cells transcriptional landscape from COVID-19 patient stratified lung injury in SARS-CoV-2 infection through impaired pulmonary surfactant metabolism
Authors: Islam Abul Bashar Mir Md. Khademul , Khan Md. Abdullah-Al-Kamran 
Published: May 2020

AbstractClinical management of COVID-19 is still complicated due to the lack of therapeutic interventions to reduce the breathing problems, respiratory complications and acute lung injury – which are the major complications of most of the mild to critically affected patients and the molecular mechanisms behind these clinical features are still largely unknown. In this study, we have used the RNA-seq gene expression pattern in the COVID-19 affected lung biopsy cells and compared it with the effects observed in typical cell lines infected with SARS-CoV-2 and SARS-CoV. We performed functional overrepresentation analyses using these differentially expressed genes to signify the processes/pathways which could be deregulated during SARS-CoV-2 infection resulting in the symptomatic impairments observed in COVID-19. Our results showed that the significantly altered processes include inflammatory responses, antiviral cytokine signaling, interferon responses, and interleukin signaling etc. along with downmodulated processes related to lung’s functionality like-responses to hypoxia, lung development, respiratory processes, cholesterol biosynthesis and surfactant metabolism. We also found that the viral protein interacting host’s proteins involved in similar pathways like: respiratory failure, lung diseases, asthma, and hypoxia responses etc., suggesting viral proteins might be deregulating the processes related to acute lung injury/breathing complications in COVID-19 patients. Protein-protein interaction networks of these processes and map of gene expression of deregulated genes revealed that several viral proteins can directly or indirectly modulate the host genes/proteins of those lung related processes along with several host transcription factors and miRNAs. Surfactant proteins and their regulators SPD, SPC, TTF1 etc. which maintains the stability of the pulmonary tissue are found to be downregulated through viral NSP5, NSP12 that could lead to deficient gaseous exchange by the surface films. Mitochondrial dysfunction owing to the aberration of NDUFA10, NDUFAF5, SAMM50 etc. by NSP12; abnormal thrombosis in lungs through atypical PLAT, EGR1 functions by viral ORF8, NSP12; dulled hypoxia responses due to unusual shift in HIF-1 downstream signaling might be the causative elements behind the acute lung injury in COVID-19 patients. Our study put forward a distinct mechanism of probable virus induced lung damage apart from cytokine storm and advocate the need of further research for alternate therapy in this direction.
A low-cost pipeline for soil microbiome profiling
Authors: Bollmann-Giolai Anita , Giolai Michael , Heavens Darren , Macaulay Iain , Malone Jacob , Clark Matthew D. 
Published: May 2020

AbstractBackgroundCommon bottlenecks in environmental microbiome studies are the consumable and personnel costs necessary for genomic DNA extraction and sequencing library construction. This is harder for challenging environmental samples such as soil, which is rich in PCR inhibitors. To address this, we have established a low-cost genomic DNA extraction method for inhibitor rich samples alongside an Illumina-compatible 16S and ITS rRNA gene amplicon library preparation workflow that uses common laboratory equipment. We evaluated the performance of our genomic DNA extraction method against two leading commercial soil genomic DNA kits (MoBio PowerSoil® and MP Biomedicals™ FastDNA™ SPIN) and a recently published non-commercial extraction method by Zou et al. (2017). Our benchmarking experiment used four different soil types (coniferous, broad leafed, and mixed forest plus a standardised cereal crop compost mix) assessing the quality and quantity of the extracted genomic DNA by analysing sequence variants of 16S V4 and ITS rRNA amplicons.ResultsWe found that our genomic DNA extraction method compares well to both commercially available genomic DNA extraction kits in DNA quality and quantity. The MoBio PowerSoil® kit, which relies on silica column-based DNA extraction with extensive washing delivered the cleanest genomic DNA e.g. best A260:A280 and A260:A230 absorbance ratios. The MP Biomedicals™ FastDNA™ SPIN kit, which uses a large amount of binding material, yielded the most genomic DNA. Our method fits between the two commercial kits, producing both good yields and clean genomic DNA with fragment sizes of approximately 10 kb. Comparative analysis of detected amplicon sequence variants shows that our method correlates well with the two commercial kits.ConclusionHere we present a low-cost genomic DNA extraction method for inhibitor rich sample types such as soil that can be coupled to an Illumina-compatible simple two step amplicon library construction workflow for 16S V4 and ITS marker genes. Our method delivers high quality genomic DNA at a fraction of the cost of commercial kits and enables cost-effective, large scale amplicon sequencing projects. Notably our extracted gDNA molecules are long enough to be suitable for downstream techniques such as full gene sequencing or even metagenomics shotgun approaches using long reads (PacBio or Nanopore), 10x Genomics linked reads, Dovetail genomics etc.
Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T
Authors: Wang Chaoyue , Foxley Sean , Ansorge Olaf , Bangerter-Christensen Sarah , Chiew Mark , Leonte Anna , Menke Ricarda AL , Mollink Jeroen , Pallebage-Gamarallage Menuka , Turner Martin R , Miller Karla L , Tendler Benjamin C. 
Published: May 2020

AbstractSusceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology.Twelve post-mortem brains were scanned with a multi-echo gradient echo sequence at 7T, from which susceptibility and R2* maps were generated. Semi-quantitative histological analysis for ferritin (the principal iron storage protein) and myelin proteolipid protein was performed in the primary motor, anterior cingulate and visual cortices.Magnetic susceptibility and R2* values in primary motor cortex were higher in ALS compared to control brains. Magnetic susceptibility and R2* showed positive correlations with both myelin and ferritin estimates from histology. Four out of nine ALS brains exhibited clearly visible hyperintense susceptibility and R2* values in the primary motor cortex.Our results demonstrate the potential for MRI-histology studies in whole, fixed post-mortem brains to investigate the biophysical source of susceptibility weighted MRI signals in neurodegenerative diseases like ALS.
3D Additive Manufactured Composite Scaffolds with Antibiotic-loaded Lamellar Fillers for Bone Infection Prevention and Tissue Regeneration
Authors: Cámara-Torres María , Duarte Stacy , Sinha Ravi , Egizabal Ainhoa , Álvarez Noelia , Bastianini Maria , Sisani Michele , Scopece Paolo , Scatto Marco , Bonetto Alessandro , Marcomini Antonio , Sanchez Alberto , Patelli Alessandro , Mota Carlos , Moroni Lorenzo 
Published: May 2020

AbstractBone infections following open bone fracture or implant surgery remain a challenge in the orthopedics field. In order to avoid high doses of systemic drug administration, optimized local antibiotic release from scaffolds is required. 3D additive manufactured (AM) scaffolds made with biodegradable polymers are ideal to support bone healing in non-union scenarios and can be given antimicrobial properties by the incorporation of antibiotics. In this study, ciprofloxacin and gentamicin intercalated in the interlamellar spaces of magnesium aluminum layered double hydroxides (MgAl) and α-zirconium phosphates (ZrP), respectively, are dispersed within a thermoplastic polymer by melt compounding and subsequently processed via high temperature melt extrusion AM (∼190 °C) into 3D scaffolds. The inorganic fillers enable a sustained antibiotics release through the polymer matrix, controlled by antibiotics counterions exchange or pH conditions. Importantly, both antibiotics retain their functionality after the manufacturing process at high temperatures, as verified by their activity against both Gram + and Gram − bacterial strains. Moreover, scaffolds loaded with filler-antibiotic do not impair human mesenchymal stromal cells osteogenic differentiation, allowing matrix mineralization and the expression of relevant osteogenic markers. Overall, these results suggest the possibility of fabricating dual functionality 3D scaffolds via high temperature melt extrusion for bone regeneration and infection prevention.
Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates
Authors: Fei Xue , Bell Tristan A , Barkow Sarah R , Baker Tania A , Sauer Robert T 
Published: May 2020

ABSTRACTWhen ribosomes fail to complete normal translation, all cells have mechanisms to ensure degradation of the resulting partial proteins to safeguard proteome integrity. InE. coliand other eubacteria, the tmRNA system rescues stalled ribosomes and adds an ssrA tag or degron to the C-terminus of the incomplete protein, which directs degradation by the AAA+ ClpXP protease. Here, we present cryo-EM structures of ClpXP bound to the ssrA degron. C-terminal residues of the ssrA degron initially bind in the top of an otherwise closed ClpX axial channel and subsequently move deeper into an open channel. For short-degron protein substrates, we show that unfolding can occur directly from the initial closed-channel complex. For longer-degron substrates, our studies illuminate how ClpXP transitions from specific recognition into a nonspecific unfolding and translocation machine. Many AAA+ proteases and protein-remodeling motors are likely to employ similar multistep recognition and engagement strategies.
Mobility and infectiousness in the spatial spread of an emerging fungal pathogen
Authors: Langwig Kate E. , White J. Paul , Parise Katy L. , Kaarakka Heather M. , Redell Jennifer A. , DePue John E. , Scullon William H. , Foster Jeffrey T. , Kilpatrick A. Marm , Hoyt Joseph R. 
Published: May 2020

AbstractEmerging infectious diseases can have devastating effects on host communities, causing population collapse and species extinctions. The timing of novel pathogen arrival into naïve species communities can have consequential effects that shape the trajectory of epidemics through populations. Pathogen introductions are often presumed to occur when hosts are highly mobile. However, spread patterns can be influenced by a multitude of other factors including host body condition and infectiousness.White-nose syndrome (WNS) is a seasonal emerging infectious disease of bats, which is caused by the fungal pathogenPseudogymnoascus destructans. Within-site transmission ofP. destructansprimarily occurs over winter, however the influence of bat mobility and infectiousness on the seasonal timing of pathogen spread to new populations is unknown. We combined data on host population dynamics and pathogen transmission from 22 bat communities to investigate the timing of pathogen arrival and the consequences of varying pathogen arrival times on disease impacts.We found that midwinter arrival of the fungus predominated spread patterns, suggesting that bats were most likely to spreadP. destructanswhen they are highly infectious, but have reduced mobility. In communities whereP. destructanswas detected in early winter, one species suffered higher fungal burdens and experienced more severe declines than at sites where the pathogen was detected later in the winter, suggesting that the timing of pathogen introduction had consequential effects for some bat communities. We also found evidence of source-sink population dynamics over winter, suggesting some movement among sites occurs during hibernation, even though bats at northern latitudes were thought to be fairly immobile during this period. Winter emergence behavior symptomatic of white-nose syndrome may further exacerbate these winter bat movements to uninfected areas.Our results suggest that low infectiousness during host migration may have reduced the rate of expansion of this deadly pathogen, and that elevated infectiousness during winter plays a key role in seasonal transmission. Furthermore, our results highlight the importance of both accurate estimation of the timing of pathogen spread and the consequences of varying arrival times to prevent and mitigate the effects of infectious diseases.
Comparative severity analysis of colitis in C57BL/6 than BALB/c mice: A novel and rapid model of DSS induced colitis
Authors: Mukhopadhyay Sohini , Aich Palok 
Published: May 2020

AbstractColitis is a complex and multifactorial disease with unknown etiology. To understand colitis, a number of models were developed in mouse. Colitis, in these models, was induced using either chemicals or select bacteria. Dextran sulfate sodium (DSS) induced colitis model was used widely, over other models, because of the simpler properties of DSS and similarities of the model with colitis in humans. The available models of DSS induced colitis require either longer time to understand the chronic stages of the disease or a shorter time period to study the acute phase. Currently, no composite models exist that can be used to study the acute, chronic and recovery stages of colitis within a reasonably shorter period of time. In the current study, we have developed a newer model system in two differently immune biased (Th-1 and Th-2) mice strains using DSS. We have developed the DSS model to compare the response in C57BL/6 (Th1 biased) and BALB/c (Th2 biased) mice models. We have standardized the dosage for both C57BL/6 and BALB/c mice with zero mortality rates. Using the model developed we studied the acute, chronic and recovery phases of colitis. The differential responses of C57BL/6 and BALB/c revealed that the disease was more severe in C57Bl/6. BALB/c, on the contrary, recovered from the diseased condition more quickly. The current report will further help to unravel the disease etiology based on immunological background of the host.
Werewolf, there wolf: variants inHairlessassociated with hypotrichia and roaning in the lykoi cat breed
Authors: Buckley Reuben M. , Gandolfi Barbara , Creighton Erica K. , Pyne Connor A. , LeRoy Michelle L. , Senter David A. , Bouhan Delia M. , Gobble Johnny R. , Abitbol Marie , Lyons Leslie A. ,   99 Lives Consortium
Published: May 2020

AbstractA variety of cat breeds have been developed via novelty selection on aesthetic, dermatological traits, such as coat colors and fur types. A recently developed breed, the lykoi, was bred from cats with a sparse hair coat with roaning, implying full color and all white hairs. The lykoi phenotype is a form of hypotrichia, presenting as significant reduction in the average numbers of follicles per hair follicle group as compared to domestic shorthair cats, a mild to severe perifollicular to mural lymphocytic infiltration in 77% of observed hair follicle groups, and the follicles are often miniaturized, dilated, and dysplastic. Whole genome sequencing was conducted on a single lykoi cat that was a cross between two independently ascertained lineages. Comparison to the 99 Lives dataset of 194 non-lykoi cats suggested two variants in the cat homolog forHairless(HR:lysine demethylase and nuclear receptor corepressor) as candidate causal variants. The lykoi cat was a compound heterozygote for two loss of function variants inHR, an exon 3 c.1255_1256dupGT (chrB1:36040783), which should produce a stop codon at amino acid 420 (p.Gln420Serfs*100) and, an exon 18 c.3389insGACA (chrB1:36051555), which should produce a stop codon at amino acid position 1130 (p.Ser1130Argfs*29). Ascertainment of 14 additional cats from founder lineages from Canada, France and different areas of the USA identified four additional loss of functionHRvariants likely causing the highly similar phenotypic hair coat across the diverse cats. The novel variants inHRfor cat hypotrichia can now be established between minor differences in the phenotypic presentations.
Oxytocin signals via Gi and Gq to drive persistent CA2 pyramidal cell firing and strengthen CA3-CA1 neurotransmission
Authors: Eyring Katherine W. , Liu Jingjing , König Gabriele M. , Hidema Shizu , Nishimori Katsuhiko , Kostenis Evi , Tsien Richard W. 
Published: May 2020

AbstractThe oxytocin receptor (OXTR) is concentrated in specific brain regions, exemplified by hippocampal subregion CA2, that support social information processing. Oxytocinergic modulation of CA2 directly affects social behavior, yet how oxytocin regulates activity in CA2 remains incompletely understood. We found that OXTR stimulation acts via closure of M-current potassium channels in all OXT-sensitive CA2 neurons. M-current inhibition was persistent in CA2 pyramidal cells, whose prolonged burst firing required functional coupling of the OXTR to both Gαq and Gαi proteins. Other neuromodulators acted via distinct patterns of G-protein signaling to induce CA2 pyramidal neuron burst firing, underscoring its likely importance. CA2 burst firing impacted hippocampal subregion CA1 wherestratum oriens-resident CA1 interneurons were targeted more strongly than CA1 pyramidal cells. Oxytocinergic modulation of interneurons, via CA2 pyramidal cell input and directly, triggered a long-lasting enhancement of CA3-CA1 transmission. Thus, transient activation of oxytocinergic inputs may initiate long-lasting recording of social information.
Diverse deep neural networks all predict human IT well, after training and fitting
Authors: Storrs Katherine R. , Kietzmann Tim C. , Walther Alexander , Mehrer Johannes , Kriegeskorte Nikolaus 
Published: May 2020

ABSTRACTDeep neural networks (DNNs) trained on object recognition provide the best current models of high-level visual areas in the brain. What remains unclear is how strongly network design choices, such as architecture, task training, and subsequent fitting to brain data contribute to the observed similarities. Here we compare a diverse set of nine DNN architectures on their ability to explain the representational geometry of 62 isolated object images in human inferior temporal (hIT) cortex, as measured with functional magnetic resonance imaging. We compare untrained networks to their task-trained counterparts, and assess the effect of fitting them to hIT using a cross-validation procedure. To best explain hIT, we fit a weighted combination of the principal components of the features within each layer, and subsequently a weighted combination of layers. We test all models across all stages of training and fitting for their correlation with the hIT representational dissimilarity matrix (RDM) using an independent set of images and subjects. We find that trained models significantly outperform untrained models (accounting for 57% more of the explainable variance), suggesting that features representing natural images are important for explaining hIT. Model fitting further improves the alignment of DNN and hIT representations (by 124%), suggesting that the relative prevalence of different features in hIT does not readily emerge from the particular ImageNet object-recognition task used to train the networks. Finally, all DNN architectures tested achieved equivalent high performance once trained and fitted. Similar ability to explain hIT representations appears to be shared among deep feedforward hierarchies of nonlinear features with spatially restricted receptive fields.
Robust decomposition of cell type mixtures in spatial transcriptomics
Authors: Cable Dylan M. , Murray Evan , Zou Luli S. , Goeva Aleksandrina , Macosko Evan Z. , Chen Fei , Irizarry Rafael A. 
Published: May 2020

AbstractSpatial transcriptomic technologies measure gene expression at increasing spatial resolution, approaching individual cells. However, a limitation of current technologies is that spatial measurements may contain contributions from multiple cells, hindering the discovery of cell type-specific spatial patterns of localization and expression. Here, we develop Robust Cell Type Decomposition (RCTD,https://github.com/dmcable/RCTD), a computational method that leverages cell type profiles learned from single-cell RNA sequencing data to decompose mixtures, such as those observed in spatial transcriptomic technologies. Our approach accounts for platform effects introduced by systematic technical variability inherent to different sequencing modalities. We demonstrate RCTD provides substantial improvement in cell type assignment in Slide-seq data by accurately reproducing known cell type and subtype localization patterns in the cerebellum and hippocampus. We further show the advantages of RCTD by its ability to detect mixtures and identify cell types on an assessment dataset. Finally, we show how RCTD’s recovery of cell type localization uniquely enables the discovery of genes within a cell type whose expression depends on spatial environment. Spatial mapping of cell types with RCTD has the potential to enable the definition of spatial components of cellular identity, uncovering new principles of cellular organization in biological tissue.
Screening for Potential Interaction Partners with Surface Plasmon Resonance Imaging Coupled to MALDI Mass Spectrometry
Authors: Anders Ulrike , Gulotti-Georgieva Maya , Zelger-Paulus Susann , Hibti Fatima-Ezzahra , Frydman Chiraz , Suckau Detlev , Sigel Roland K.O. , Zenobi Renato 
Published: May 2020

ABSTRACTWe coupled SPR imaging (SPRi) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) to identify new potential RNA binders. Here, we improve this powerful method, especially by optimizing the proteolytic digestion (type of reducing agent, its concentration, and incubation time), to work with complex mixtures, specifically a lysate of the rough mitochondrial fraction from yeast. The advantages of this hyphenated method compared to column-based or separate analyses are (i) rapid and direct visual readout from the SPRi array, (ii) possibility of high-throughput analysis of different interactions in parallel, (iii) high sensitivity, and (iv) no sample loss or contamination due to elution or micro-recovery procedures. The model system used is a catalytically active RNA (group IIB intron fromSaccharomyces cerevisiae, Sc.ai5γ) and its cofactor Mss116. The protein supports the RNA folding process and thereby the subsequent excision of the intronic RNA from the coding part. Using the novel approach of coupling SPR with MALDI MS, we report the identification of potential RNA-binding proteins from a crude yeast mitochondrial lysate in a non-targeted approach. Our results show that proteins other than the well-known cofactor Mss116 interact withSc.ai5γ (Dbp8, Prp8, Mrp13, and Cullin-3), suggesting that the intron folding and splicing are regulated by more than one cofactorin vivo.Graphical abstractAuthor contributionUlrike Anders and Maya Gulotti-Georgieva contributed equally to this work.