bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical re-evaluation of the slope factor of the operational model of agonism: Do not exponentiate operational efficacy
Authors: Jakubík Jan 
Published: April 2021

AbstractAlthough being a relative term, agonist efficacy is a cornerstone in the proper assessment of agonist selectivity and signalling bias. The operational model of agonism (OMA) has become successful in the determination of agonist efficacies and ranking them. In 1983, Black and Leff introduced the slope factor to the OMA to make it more flexible and allow for fitting steep as well as flat concentration-response curves. Functional analysis of OMA demonstrates that the slope factor implemented by Black and Leff affects relationships among parameters of the OMA. Fitting of the OMA with Black & Leff slope factor to concentration-response curves theoretical model-based data resulted in wrong estimates of operational efficacy and affinity. In contrast, fitting the OMA modified by the Hill coefficient to the same data resulted in correct estimates of operational efficacy and affinity. Therefore, OMA modified by the Hill coefficient should be preferred over the Black & Leff equation for ranking of agonism and subsequent analysis, like quantification of signalling bias, when concentration-response curves differ in the slope factor and mechanism of action is known. Otherwise. Black & Leff equation should be used with extreme caution acknowledging potential pitfalls.
Genome archaeology of two laboratorySalmonella enterica entericasv Typhimurium
Authors: Zaworski Julie , Dagva Oyut , Kingston Anthony W , Fomenkov Alexey , Morgan Richard D. , Bossi Lionello , Raleigh Elisabeth A. 
Published: April 2021

AbstractThe Salmonella research community has used strains and bacteriophages over decades, exchanging useful new isolates among laboratories for study of cell surface antigens, metabolic pathways and restriction-modification studies. Here we present the sequences of two laboratorySalmonellastrains (STK005, an isolate of LB5000; and its descendant ER3625). In the ancestry of LB5000, segments of ~15 and ~42 kb were introduced fromSalmonella entericasv Abony 103 intoSalmonella entericasv Typhimurium LT2, forming strain SD14; this strain is thus a hybrid ofS. entericaisolates. Strains in the SD14 lineage were used to define flagellar antigens from the 1950s to the 1970s, and to define three restriction-modification systems from the 1960s to the 1980s. LB5000 was also used as host in phage typing systems used by epidemiologists. In the age of cheaper and easier sequencing, this resource will provide access to the sequence that underlies the extensive literature.
Diaphragm muscle fibrosis involves changes in collagen organization with mechanical implications in Duchenne Muscular Dystrophy
Authors: Sahani Ridhi , Wallace C. Hunter , Jones Brian K. , Blemker Silvia S. 
Published: April 2021

AbstractIn Duchenne muscular dystrophy (DMD), diaphragm muscle dysfunction results in respiratory insufficiency, a leading cause of death in patients. Increased muscle stiffness occurs with buildup of fibrotic tissue, characterized by excessive accumulation of extracellular matrix (ECM) components such as collagen. However, changes in mechanical properties are not explained by collagen amount alone and we must consider the complex structure and mechanics of fibrotic tissue. The goals of our study were to (1) determine if and how collagen organization changes with the progression of DMD in diaphragm muscle tissue, and (2) predict how collagen organization influences the mechanical properties of ECM. We first visualized collagen structure with scanning electron microscopy (SEM) images and then developed an analysis framework to quantify collagen organization and generate image-based finite-element models. The image analysis revealed significant age- and disease-dependent increases in collagen fiber straightness and alignment, ranging from 4.7 to 13.4%, but collagen fibers retained a transverse orientation relative to muscle fibers. The mechanical models predicted significant age- and disease-dependent increases in transverse effective stiffness and average stress, ranging from 8.8 to 12.4%. Additionally, both healthy and diseased models revealed an increase in transverse stiffness relative to longitudinal stiffness, with significant age- and disease-dependent increases in the ratio of transverse to longitudinal stiffness, ranging from 19.7 to 24.5%. This study revealed changes in diaphragm ECM structure and mechanics during the progression of disease in themdxmuscular dystrophy mouse phenotype, highlighting the need to consider the role of collagen organization on diaphragm muscle function.
An open source statistical and data processing toolbox for wide-field optical imaging in mice
Authors: Brier Lindsey M. , Culver Joseph P. 
Published: April 2021

AbstractWide-field optical imaging (WOI) produces concurrent hemodynamic and cell-specific calcium recordings across the entire cerebral cortex. There have been multiple studies using WOI to image mouse models with various environmental or genetic manipulations to understand various diseases. Despite the obvious utility of pursuing mouse WOI alongside human functional magnetic resonance imaging (fMRI), and the multitude of analysis toolboxes in the fMRI literature, there is not an available open-source, user-friendly data processing and statistical analysis toolbox for WOI data. Here, we present our MATLAB toolbox for pre-processing WOI data, as described and adapted to combine processing techniques from multiple WOI groups. Additionally, we provide multiple data analysis packages and translate two commonly used statistical approaches from the fMRI literature to the WOI data. To illustrate the utility, we demonstrate the ability of the processing and analysis framework to detect a well-established deficit in a mouse model of stroke. Additionally, we evaluate resting state data in healthy mice.
Drought resilience of long term dry-farmed grapevines(Vitis vinifera L.)
Authors: Pagay Vinay , Furlan Tarita S. , Kidman Catherine M. , Nagahatenna Dilrukshi 
Published: April 2021

AbstractWe explored the long-term drought resilience of field-grown unirrigated (or dry-grown) grapevines of pre-clonal origin from shallow (SR) and deep (DR) soils representing low and high soil water availability, respectively, in a warm, Mediterranean climate. Despite lower soil moisture available to SR vines, both deep and shallow-rooted vines had similar vine water status, based on measurements of midday stem water potential (Ψs), and leaf net photosynthesis (An). Due to the lower stomatal conductance (gs), SR had higher intrinsic water use efficiency (WUEi) than DR, however the carbon isotope ratio (δ13C) of the fruit at harvest was similar between the two groups. Our observations suggest a degree of drought adaptation in the SR vines resulting from multi-decadal cyclical droughts. Overall, we demonstrate that pre-clonal Cabernet Sauvignon grapevines dry-grown in shallow soils have an enhanced resilience to drought compared to dry-grown vines in deep soils. This study has implications for selection of crop genetic material in a changing climate.
me31Bregulates stem cell homeostasis by preventing excess dedifferentiation in theDrosophilamale germline
Authors: Jensen Lindy , Venkei Zsolt G. , Watase George J. , Bisai Bitarka , Pletcher Scott , Lee Cheng-Yu , Yamashita Yukiko M. 
Published: April 2021

AbstractTissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulatorme31Bplays a critical role in preventing excess dedifferentiation in theDrosophilamale germline: in the absence ofme31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation ofnos,a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.
Human pulmonary artery endothelial cells upregulate ACE2 expression in response to iron-regulatory elements: potential implications for SARS-CoV-2 infection of vascular endothelial cells
Authors: K Toe Quezia , Issitt Theo , S Mahomed Abdul , Panselinas Ioannis , Almaghlouth Fatma , Burke-Gaffney Anne , Wort S John , J Quinlan Gregory 
Published: April 2021

AbstractEmerging studies from the ongoing covid-19 pandemic have implicated vascular dysfunction and endotheliitis in many patients presenting with severe disease. However, there is limited evidence for the expression of ACE2 (the principal co-receptor for Sars-Cov-2 cellular attachment) in vascular endothelial cells which has prompted the suggestion that the virus does not infect these cell types. However, the studies presented here demonstrate enhanced expression of ACE2 at the level of both mRNA and protein, in human pulmonary artery endothelial cells (PAECs) challenged with either IL-6 or hepcidin. Notably elevated levels both these iron-regulatory elements have been described in Covid-19 patients with severe disease and are further associated with morbidity and mortality. Additionally, levels of both IL-6 and hepcidin are often elevated in the elderly and in chronic disease settings, these populations being at greater risk of adverse outcomes from Sars-Cov-2 infection. A role for IL-6 and hepcidin as modulators of ACE2 expression seems plausible, additional, studies are required to determine if viral infection can be demonstrated in PAECs challenged with either of these iron-regulatory elements.
The role of L-arabinose metabolism forEscherichia coliO157:H7 in edible plants
Authors: Crozier Louise , Marshall Jacqueline , Holmes Ashleigh , Wright Kathryn , Rossez Yannick , Merget Bernhard , Humphries Sonia , Toth Ian , Jackson Robert Wilson , Holden Nicola Jean 
Published: April 2021

AbstractArabinose is a major plant aldopentose in the form of arabinans complexed in cell wall polysaccharides or glycoproteins (AGP), but comparatively rare as a monosaccharide. L-arabinose is an important bacterial metabolite, accessed by pectolytic microorganisms such asPectobacterium atrosepticumvia pectin and hemicellulose degrading enzymes. However, not all plant-associated microbes encode cell wall degrading enzymes, yet can metabolise L-arabinose, raising questions about their use of and access to the glycan in plants. Therefore, we examined L-arabinose metabolism in the food-borne pathogenEscherichia coliO157:H7 (isolate Sakai) during its colonisation of plants. L-arabinose metabolism (araBA) and transport (araF) genes were activated at 18 °Cin vitroby L-arabinose and expressed over prolonged periodsin planta. Although deletion ofaraBADdid not impact the colonisation ability ofE. coliO157:H7 (Sakai) on plants,araAwas induced on exposure to spinach cell wall polysaccharides. Furthermore, debranched and arabinan oligosaccharides inducedarametabolism gene expressionin vitro, and stimulated modest proliferation, while immobilised pectin did not. Thus,E. coliO157:H7 (Sakai) can utilise pectin/AGP- derived L-arabinose as a metabolite, but differs fundamentally inaragene organisation, transport and regulation from the related pectinolytic speciesP. atrosepticum, reflective of distinct plant- associated lifestyles.
Emotion Recognition in a Multi-Componential Framework: The Role of Physiology
Authors: Menétrey Maëlan Q. , Mohammadi Gelareh , Leitão Joana , Vuilleumier Patrik 
Published: April 2021

ABSTRACTEmotions are rich and complex experiences involving various behavioral and physiological responses. While many empirical studies have focused on discrete and dimensional representations of emotions, these representations do not fully reconcile with recent neuroscience studies that increasingly suggest a multi-process mechanism underlying emotional experience. Moreover, the latter view accords with psychological theories that consider emotions as multicomponent phenomena, such as appraisal theories. Although there is no complete consensus on the specific components of emotions and fundamental principles defining their organization, the Component Process Model (CPM) is well established framework describing an emotion as a dynamic process with five major highly interrelated components: cognitive appraisal, expression, motivation, physiology and feeling. Yet, few studies have systematically investigated a range of discrete emotions through this full multi-componential view. In the present study, we therefore elicited various emotions during movie watching and measured their manifestation across these components. Our primary goal was to investigate the relationship between physiological measures and the theoretically defined components of emotions. In addition, we also investigated whether discrete emotions could be predicted from information provided by the multicomponent response patterns, as well as the specific contributions of each component in such predictions. Results suggest that physiological features are interrelated to all other components of emotion, but the least significant predictors for emotion classification. Overall, emotion prediction was significantly higher when classifiers were trained with all five components. The findings therefore support a description of emotion as a dynamic multicomponent process, in which the emergence of a conscious feeling state requires the integration of all the components.
The neuroblast timer genenubbinexhibits functional redundancy with gap genes to regulate segment identity inTribolium
Authors: Tidswell Olivia RA , Benton Matthew A , Akam Michael E 
Published: April 2021

AbstractInDrosophila, segmentation genes of the gap class form a regulatory network that positions segment boundaries and assigns segment identities. This gene network shows striking parallels with another gene network known as the neuroblast timer series. The neuroblast timer geneshunchback, Krüppel, nubbin,andcastorare expressed in temporal sequence in neural stem cells to regulate the fate of their progeny. These same four genes are expressed in corresponding spatial sequence along theDrosophilablastoderm. The first two,hunchbackandKrüppel, are canonical gap genes, butnubbinandcastorhave limited or no roles inDrosophilasegmentation. Whethernubbinandcastorregulate segmentation in insects with the ancestral, sequential mode of segmentation remains largely unexplored.We have investigated the expression and functions ofnubbinandcastorduring segment patterning in the sequentially-segmenting beetleTribolium. Using multiplex fluorescentin situhybridisation, we show thatTc-hunchback,Tc-Krüppel,Tc-nubbinandTc-castorare expressed sequentially in the segment addition zone ofTribolium, in the same order as they are expressed inDrosophilaneuroblasts. Furthermore, simultaneous disruption of multiple genes reveals thatTc-nubbinregulates segment identity, but does so redundantly with two previously described gap/gap-like genes,Tc-giantandTc-knirps. Knockdown of two or more of these genes results in the formation of up to seven pairs of ectopic legs on abdominal segments. We show that this homeotic transformation is caused by loss of abdominal Hox gene expression, likely due to expandedTc-Krüppelexpression. Our findings support the theory that the neuroblast timer series was co-opted for use in insect segment patterning, and contribute to our growing understanding of the evolution and function of the gap gene network outside ofDrosophila.
Resilience of riparian vegetation composition and diversity following cessation of livestock grazing in northeastern Oregon
Authors: Kauffman J Boone , Coleman Greg , Otting Nick , Lytjen Danna , Nagy Dana , Beschta Robert L. 
Published: April 2021

AbstractRiparian ecosystem restoration has been accomplished through exclusion of livestock using corridor fencing along hundreds of kilometers of streams in the western USA, for the benefit of riparian-obligate wildlife and endangered fishes. Yet few studies have evaluated shifts in the vegetation composition and diversity following the cessation of livestock impacts. We sampled riparian vegetation composition along 11-paired grazed and ungrazed (exclosed) stream reaches in northeastern Oregon, USA. Exclosure ages ranged from 2 to >30 years and grazing treatments varied from light grazing every one out of three years to heavy season-long grazing. Species richness and diversity was higher in the ungrazed reaches (p =0.002). The abundance of native sedges (Carexspp.) and broad-leaved forbs were also significantly (p < 0.05) greater in ungrazed areas. In contrast, exotic species adapted to grazing such asPoa pratensisandTrifolium repenswere more abundant in grazed stream reaches. The prevalence of hydrophytic species significantly increased (p ≤ 0.01) in ungrazed reaches, (based on wetland species indicator scores), indicating that wetland-dominated communities within the ungrazed stream reaches were replacing ones adapted to drier environments. The increased abundance of facultative and wetland-obligate species in ungrazed reaches compared to grazed reaches suggests that livestock grazing exacerbates those climate change effects also leading to warmer and drier conditions. Further, riparian-obligate shrub cover along the streambank was higher in 7 of 8 exclosures that were older than 5 years. As a restoration approach the inherent resilience of riparian ecosystems exhibited in ungrazed riparian zones suggest positive feedbacks to other beneficial ecosystem processes such as increased species and habitat diversity, increased carbon sequestration, enhanced allochthonous inputs and greater sediment retention, that would affect the aquatic and terrestrial biota, water quality, and stream morphology.
Characterization of light penetration through brain tissue, for optogenetic stimulation
Authors: Johnson Emily L. , Walsh Darren , Hutchings Frances , Palmini Rolando Berlinguer , Ponon Nikhil , O’Neill Anthony , Jackson Andrew , Degenaar Patrick , Trevelyan Andrew J. 
Published: April 2021

AbstractThe recent development of optogenetic tools, to manipulate neuronal activity using light, provides opportunities for novel brain-machine interface (BMI) control systems for treating neurological conditions. An issue of critical importance, therefore, is how well light penetrates through brain tissue. We took two different approaches to estimate light penetration through rodent brain tissue. The first employed so-called “nucleated patches” from cells expressing the light-activated membrane channel, channelrhodopsin (ChR2). By recording light-activated currents, we used these nucleated patches as extremely sensitive, microscopic, biological light-meters, to measure light penetration through 300-700µm thick slices of rodent neocortical tissue. The nucleated patch method indicates that the effective illumination drops off with increasing tissue thickness, corresponding to a space constant of 317µm (95% confidence interval between 248-441µm). We compared this with measurements taken from directly visualizing the illumination of brain tissue, orthogonal to the direction of the light. This yielded a contour map of reduced illumination with distance, which along the direction of light delivery, had a space constant,τ453µm. This yields a lower extinction coefficient, µe(the reciprocal ofτ, ∼3mm-1) than previous estimates, implying better light penetration from LED sources than these earlier studies suggest.
Quantitative mapping of cerebral oxygen metabolism using breath-hold calibrated fMRI
Authors: Germuska M , Stickland RC , Chiarelli AM , Chandler HL , Wise RG 
Published: April 2021

AbstractMagnetic resonance imaging (MRI) offers the possibility to non-invasively map the rate of cerebral metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. Existing methods of mapping CMRO2, based on respiratory modulation of arterial spin labelling (ASL) and blood oxygen level dependent (BOLD) signals, require lengthy acquisitions and independent modulation of both arterial oxygen and carbon dioxide levels. Here, we present a new simplified method for mapping the rate of cerebral oxygen metabolism that can be performed using a simple breath-holding paradigm. The method incorporates flow-diffusion modelling of oxygen transport and physiological constraints to create a non-linear mapping between the maximum BOLD signal, M, baseline blood flow (CBF0), and CMRO2. A gradient boosted decision tree is used to learn this mapping directly from simulated MRI data. Modelling studies demonstrate that the proposed method is robust to variation in cerebral physiology and metabolism. This new gas-free methodology offers a rapid and pragmatic alternative to existing dual-calibrated methods, removing the need for specialist respiratory equipment and long acquisition times. In-vivo testing of the method, using an 8-minute 45 second protocol of repeated breath-holding, was performed on 15 healthy volunteers, producing quantitative maps of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and CMRO2.
Assessing bivalve phylogeny using Deep Learning and Computer Vision approaches
Authors: Kiel Steffen 
Published: April 2021

ABSTRACTPhylogenetic analyses using morphological data currently require hand-crafted character matrices, limiting the number of taxa that can be included. Here I explore how Deep Learning and Computer Vision approaches typically applied to image classification tasks, may be used to infer phylogenetic relationships among bivalves. A convolutional neural network (CNN) was trained on thousands of images showing species of 75 bivalve families. The predictions of the CNN on a large number of bivalve images are then interpreted as an indication of how similar these bivalves are to each other, are averaged by the families to which the species belonged, and visualized in a cluster diagram. In this cluster diagram, significantly more families clustered with members of their subclasses than expected by chance, confirming the feasibility of the approach. To address the issue of convergent evolution, two further CNNs were trained, on the same images but grouped by the orders and subclasses to which the species belonged. Combining predictions for the same images but on different taxonomic levels improved the inferred phylogenetic relationships also of families that the CNNs had not been trained on. Finally, this combined tree is merged with five published phylogenetic trees into a supertree, representing the largest single phylogeny of the Bivalvia to date, encompassing 128 families, including six exclusively fossil families and nine extant families for which presently no molecular data are available. Issues inherent to the approach and suggestions for future directions are discussed.