bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-organization of Tissue Growth by Interfacial Mechanical Interactions in Multi-layered Systems
Authors: Chen Tailin , Zhao Yan , Zhao Xinbin , Li Shukai , Cao Jialing , Du Jing , Cao Yanping , Fan Yubo 
Published: March 2021

AbstractMorphogenesis is a spatially and temporally regulated process involved in various physiological and pathological transformations. In addition to the associated biochemical factors, the physical regulation of morphogenesis has attracted increasing attention. However, the driving force of morphogenesis initiation remains elusive. Here, we show that during the growth of multi-layered tissues, morphogenetic process can be self-organized by the progression of compression gradient stemmed from the interfacial mechanical interactions between layers. In tissues with low fluidity, the compression gradient is progressively strengthened during growth and induces stratification by triggering symmetric-to-asymmetric cell division reorientation at the critical tissue size. In tissues with high fluidity, compression gradient is dynamic and induces cell junction remodelling regulated cell rearrangement leading to 2D in-plane morphogenesis instead of 3D deformation. Morphogenesis can be tuned by manipulating tissue fluidity, cell adhesion forces and mechanical properties to influence the progression of compression gradient during the development of cultured cell sheets and chicken embryos. Together, the dynamics of compression gradient arised from interfacial mechanical interaction provides a conserved mechanism underlying morphogenesis initiation and size control during tissue growth.
GDAP1 loss of function inhibits the mitochondrial pyruvate dehydrogenase complex by altering the actin cytoskeleton
Authors: Wolf Christina , Pouya Alireza , Bitar Sara , Pfeiffer Annika , Bueno Diones , Arndt Sabine , Tenzer Stefan , Dal Bello Federica , Vianello Caterina , Ritz Sandra , Schwirz Jonas , Dobrindt Kristina , Peitz Michael , Hanschmann Eva-Maria , Boussaad Ibrahim , Brüstle Oliver , Giacomello Marta , Krüger Rejko , Methner Axel 
Published: March 2021

AbstractCharcot-Marie-Tooth (CMT) disease 4A is an autosomal-recessive polyneuropathy caused by mutations of ganglioside-induced differentiation-associated protein 1 (GDAP1), a putative glutathione transferase, which affects mitochondrial shape and alters cellular Ca2+homeostasis. Here, we identify the underlying mechanism. We found that patient-derived motoneurons andGDAP1knockdown SH-SY5Y cells display two phenotypes: more tubular mitochondria and a metabolism characterized by glutamine dependence and fewer cytosolic lipid droplets. GDAP1 interacts with the actin-depolymerizing protein Cofilin-1 in a redoxdependent manner, suggesting a role for actin signaling. Consistently, GDAP1 loss causes less F-actin close to mitochondria, which restricts mitochondrial localization of the fission factor dynamin-related protein 1, instigating tubularity. Changes in the actin cytoskeleton also disrupt mitochondria-ER contact sites. This results in lower mitochondrial Ca2+levels and inhibition of the pyruvate dehydrogenase complex, explaining the metabolic changes upon GDAP1 loss of function. Together, these findings reconcile GDAP1-associated phenotypes and implicate disrupted actin signaling in CMT4A pathophysiology.
Combination ofin vivophage therapy data within silicomodel highlights key parameters for treatment efficacy
Authors: Delattre Raphaëlle , Seurat Jérémy , Haddad Feyrouz , Nguyen Thu-Thuy , Gaborieau Baptiste , Kane Rokhaya , Dufour Nicolas , Ricard Jean-Damien , Guedj Jérémie , Debarbieux et Laurent 
Published: March 2021

SummaryThe clinical (re)development of phage therapy to treat antibiotic resistant infections requires grasping specific biological properties of bacteriophages (phages) as antibacterial. However, identification of optimal dosing regimens is hampered by the poor understanding of phage-bacteria interactionsin vivo.Here we developed a general strategy couplingin vitroandin vivoexperiments with a mathematical model to characterize the interplay between phage and bacterial dynamics during pneumonia induced by a pathogenic strain ofEscherichia coli.The model estimates some key parameters for phage therapeutic efficacy, in particular the impact of dose and route of administration on phage dynamics and the synergism of phage and the innate immune response on the bacterial clearance rate. Simulations predict a low impact of the intrinsic phage characteristics in agreement with the current semi-empirical choices of phages for compassionate treatments. Model-based approaches will foster the deployment of future phage therapy clinical trials.
Taxonomic bias in AMP prediction of invertebrate peptides
Authors: Rádai Zoltán , Kiss Johanna , Nagy Nikoletta A. 
Published: March 2021

AbstractInvertebrate antimicrobial peptides (AMPs) are at the forefront in the search for agents of therapeutic utility against multi-resistant microbial pathogens, and in recent years substantial advances took place in thein silicoprediction of antimicrobial function of amino acid sequences. A yet neglected aspect is taxonomic bias in the performance of these tools. Owing to differences in the prediction algorithms and used training data sets between tools, and phylogenetic differences in sequence diversity, physicochemical properties and evolved biological functions of AMPs between taxa, notable discrepancies may exist in performance between the currently available prediction tools. Here we tested if there is taxonomic bias in the prediction power in 10 tools with a total of 20 prediction algorithms in 19 invertebrate taxa, using a data set containing 1525 AMP and 3050 non-AMP sequences. We found that most of the tools exhibited considerable variation in performance between tested invertebrate groups. Based on the per-taxa performances and on the variation in performances across taxa we provide guidance in choosing the best-performing prediction tool for all assessed taxa, by listing the highest scoring tool for each of them.
Published Anti-SARS-CoV-2 In Vitro Hits Share Common Mechanisms of Action that Synergize with Antivirals
Authors: Xing Jing , Paithankar Shreya , Liu Ke , Uhl Katie , Li Xiaopeng , Ko Meehyun , Kim Seungtaek , Haskins Jeremy , Chen Bin 
Published: March 2021

AbstractThe global efforts in the past few months have led to the discovery of around 200 drug repurposing candidates for COVID-19. Although most of them only exhibited moderate anti- SARS-CoV-2 activity, gaining more insights into their mechanisms of action could facilitate a better understanding of infection and the development of therapeutics. Leveraging large-scale drug-induced gene expression profiles, we found 36% of the active compounds regulate genes related to cholesterol homeostasis and microtubule cytoskeleton organization. The expression change upon drug treatment was further experimentally confirmed in human lung primary small airway. Following bioinformatics analysis on COVID-19 patient data revealed that these genes are associated with COVID-19 patient severity. The expression level of these genes also has predicted power on anti-SARS-CoV-2 efficacy in vitro, which led to the discovery of monensin as an inhibitor of SARS-CoV-2 replication in Vero-E6 cells. The final survey of recent drug- combination data indicated that drugs co-targeting cholesterol homeostasis and microtubule cytoskeleton organization processes more likely present a synergistic effect with antivirals. Therefore, potential therapeutics should be centered around combinations of targeting these processes and viral proteins.
Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs its Signaling Pathways in Liver and Adipose Tissue in Mice
Authors: Liu Xin-Hua , Graham Zachary A. , Harlow Lauren , Pan Jiangping , Azulai Daniella , Bauman William A. , Yarrow Joshua , Cardozo Christopher P. 
Published: March 2021

AbstractSpinal cord injury (SCI) results in dysregulation of carbohydrate and lipid metabolism; the underlying cellular and physiological mechanisms remain unclear. Fibroblast growth factor 21 (FGF21) is a circulating protein primarily secreted by the liver that lowers blood glucose levels, corrects abnormal lipid profiles, and mitigates non-alcoholic fatty liver disease. FGF21 acts via activating FGF receptor 1 and ß-klotho in adipose tissue and stimulating release of adiponectin from adipose tissue which in turn signals in the liver and skeletal muscle. We examined FGF21/adiponectin signaling after spinal cord transection in mice fed a high fat diet (HFD) or a standard mouse chow. Tissues were collected at 84 days after spinal cord transection or a sham SCI surgery. SCI reduced serum FGF21 levels and hepatic FGF21 expression, as well as β-klotho and FGF receptor-1 (FGFR1) mRNA expression in adipose tissue. SCI also reduced serum levels and adipose tissue mRNA expression of adiponectin and leptin, two major adipokines. In addition, SCI suppressed hepatic type 2 adiponectin receptor (AdipoR2) mRNA expression and PPARα activation in the liver. Post-SCI mice fed a HFD had further suppression of serum FGF21 levels and hepatic FGF21 expression. Elevated serum free fatty acid (FFA) levels after HFD feeding were observed in post-SCI mice but not in shammice, suggesting defective FFA uptake after SCI. Moreover, after SCI several genes that are implicated in insulin’s action had reduced expression in tissues of interest. These findings suggest that downregulated FGF21/adiponectin signaling and impaired responsiveness of adipose tissues to FGF21 may, at least in part, contribute to the overall picture of metabolic dysfunction after SCI.
In vivohomopropargylglycine incorporation enables nascent protein tagging, isolation and characterisation fromArabidopsis thaliana
Authors: Tivendale Nathan D. , Fenske Ricarda , Duncan Owen , Millar A. Harvey 
Published: March 2021

AbstractDetermining which proteins are actively synthesised at a given point in time and extracting them for analysis is important to understand plant responses. Here we show that the methionine (Met) analogue homopropargylglycine (HPG) enables BONCAT (Bio-Orthogonal Non-Canonical Amino acid Tagging) of proteins being synthesised in Arabidopsis plants or cell cultures, facilitating their click-chemistry enrichment for analysis. The sites of HPG incorporation could be confirmed by peptide mass spectrometry at Met-sites throughout protein AA sequences and correlation with independent studies of protein labelling with15N verified the data. We provide evidence that HPG-based BONCAT tags nascent plant proteins more efficiently than azidohomoalanine (AHA)-based BONCAT in Arabidopsis and show that AHA’s induction of Met metabolism and greater inhibition of cell growth rate than HPG likely limits AHA incorporation at Met sites in Arabidopsis. We show HPG-based BONCAT provides a verifiable method for determining which plant proteins are being synthesised at a given time point and enriches new protein molecules from the bulk protein pool for identification, quantitation and subsequent biochemical analysis. Enriched nascent polypeptides were found to contain significantly fewer common post-translationally modified residues than the same proteins from whole plant extracts, providing evidence for age-related accumulation of PTMs in plants.
TAFKAP: An improved method for probabilistic decoding of cortical activity
Authors: van Bergen R.S. , Jehee J.F.M. 
Published: March 2021

AbstractCortical activity can be difficult to interpret. Neural responses to the same stimulus vary between presentations, due to random noise and other sources of variability. This unreliable relationship to external stimuli renders any pattern of activity open to a multitude of plausible interpretations. We have previously shown that this uncertainty in cortical stimulus representations can be characterized using a probabilistic decoding algorithm, which inverts a generative model of stimulus-evoked cortical responses. Here, we improve upon this method in two important ways, which both target the precision with which the generative model can be estimated from limited, noisy training data. We show that these improvements lead to considerably better estimation of the presented stimulus and its associated uncertainty. Estimates of the presented stimulus are recovered with an accuracy that exceeds that of standard decoding methods (SVMs), and in some cases even approaches the behavioral accuracy of human observers. Moreover, the uncertainty in the decoded probability distributions better characterizes the precision of cortical stimulus information from trial to trial.
Preoptic BRS3 neurons increase body temperature and heart rate via multiple pathways
Authors: Piñol Ramón A. , Mogul Allison S. , Hadley Colleen K. , Saha Atreyi , Li Chia , Škop Vojtěch , Province Haley S. , Xiao Cuiying , Gavrilova Oksana , Krashes Michael J. , Reitman Marc L. 
Published: March 2021

AbstractThe preoptic area (POA) is a key region controlling body temperature (Tb), dictating thermogenic, cardiovascular, and behavioral responses to regulate Tb. Known POA neuronal populations reduce Tb when activated; a population that increases Tb upon activation has not yet been reported. We now identify bombesin-like receptor 3 (BRS3)-expressing POA (POABRS3) neurons as having this missing functionality. BRS3 is an orphan receptor that regulates energy and cardiovascular homeostasis, but the relevant neural circuits are incompletely understood. In mice, we demonstrate that POABRS3neuronal activation increases Tb, heart rate, and blood pressure sympathetically, via projections to the paraventricular nucleus of the hypothalamus and dorsomedial hypothalamus. Acute POABRS3inhibition reduces Tb. Long-term inactivation of POABRS3neurons increased Tb variability with exaggerated Tb changes, overshooting both increases and decreases in Tb set point. BRS3 marks preoptic populations that regulate Tb and heart rate, contribute to cold-defense and fine-tune feedback control of Tb. These findings advance understanding of homeothermy, a defining feature of mammalian biology.Graphical abstract
Diversity of an uncommon elastic hypersaline microbial mat along a small-scale transect
Authors: Espinosa-Asuar Laura , Monroy-Guzmán Camila , Madrigal-Trejo David , Navarro-Miranda Marisol , Sánchez-Pérez Jazmin , Buenrostro-Muñoz Jhoselinne , Villar Juan , Cifuentes Camargo Julián Felipe , Kalambokidis Maria , Esquivel-Hernandez Diego A. , Jasso Mariette Viladomat , Escalante Ana E. , Velez Patricia , Figueroa Mario , Cárdenas Anahí Martínez , Barahona Santiago Ramirez , Gasca-Pineda Jaime , Eguiarte Luis E. , Souza Valeria 
Published: March 2021

AbstractWe evaluated the microbial diversity and metabolome profile of an uncommon hypersaline elastic microbial mat from Cuatro Ciénegas Basin (CCB) in the Chihuahuan Desert of Coahuila, México. We collected ten samples on a small scale transect (1.5-meters) and described its microbial diversity through NGS-based ITS and 16S rDNA gene sequencing. A very low number of taxa comprised a considerable proportion of the mat and were shared across all sampling points, whereas the rare biosphere was more phylogenetically diverse (Faith’s Phylogenetic Diversity (FPD) index) and phylogenetically disperse (using a null model distribution of Phylogenetic Species Clustering (nmdPSC)) than the abundant (high read count) taxa for both analyzed libraries. We also found a distinctive metabolome profile for each sample and were able to tentatively annotate several classes of compounds with relevant biological properties.
DNA supercoiling-mediated collective behavior of co-transcribing RNA polymerases
Authors: Tripathi Shubham , Brahmachari Sumitabha , Onuchic José N. , Levine Herbert 
Published: March 2021

ABSTRACTMultiple RNA polymerases (RNAPs) transcribing a gene have been known to exhibit collective group behavior, causing the transcription elongation rate to increase with the rate of transcription initiation. Such behavior has long been believed to be driven by a physical interaction or “push” between closely spaced RNAPs. However, recent studies have posited that RNAPs separated by longer distances may cooperate via the DNA segment under transcription. Here, we present a theoretical model incorporating the mechanical coupling between RNAP translocation and the torsional response of supercoiled DNA. Using stochastic simulations, we demonstrate long-range cooperation between co-transcribing RNAPs mediated by DNA supercoiling. We find that inhibiting transcription initiation can slow down the already recruited RNAPs, in agreement with recent experimental observations, and predict that the average transcription elongation rate varies non-monotonically with the rate of transcription initiation. We further show that while RNAPs transcribing neighboring genes oriented in tandem can cooperate, those transcribing genes in divergent or convergent orientations can act antagonistically, and that such behavior holds over a large range of intergenic separations. Our model makes testable predictions, revealing how the mechanical interplay between RNAPs and the DNA they transcribe can govern a key cellular process.
Zoonotic spillover of SARS-CoV-2: mink-adapted virus in humans
Authors: Rabalski Lukasz , Kosinski Maciej , Mazur-Panasiuk Natalia , Szewczyk Boguslaw , Bienkowska-Szewczyk Krystyna , Kant Ravi , Sironen Tarja , Pyrć Krysztof , Grzybek Maciej 
Published: March 2021

ABSTRACTThe COVID-19 pandemic caused by SARS-CoV-2 started in fall 2019. A range of different mammalian species, including farmed mink, have been confirmed as susceptible to infection with this virus. We report here the spillover of mink-adapted SARS-CoV-2 from farmed mink to humans after extensive adaptation that lasted at least 3 months. We found the presence of four mutations in the S gene (that gave rise to variant: G75V, M177T, Y453F and C1247F) and others in an isolate obtained from SARS-CoV-2 positive patient.
Unmanned aircraft automatic flight control algorithm in an Immelmann manoeuvre
Authors: Rogalski Tomasz , Rzucidło Paweł , Noga Stanisław , Prusik Jacek 
Published: March 2021

Purpose
The purpose of this paper is to present the idea of automatic flight control algorithms capable of performing an Immelmann turn manoeuvre automatically. This is a case of a manoeuvre far removed from so-called standard flight. The character of this manoeuvre and the range of changes in the aircraft flight parameters restrict the application of standard control algorithms. Furthermore, the possibility of acquiring full and detailed information about the aircraft’s flight parameters is limited in such cases. This paper seeks to analyse an alternative solution that can be applied in some specific cases.

Design/methodology/approach
This paper uses theoretical discussion and breakdowns to create the basics for development of structures of control algorithms. A simplified analytical approach was applied to tune regulators and the results of the research were verified in a series of software-in-the loop computer simulations.

Findings
The structure of the control system enabling aerobatic flight (with the Immelmann turn as the selected example) was identified and the method for tuning the regulators is also presented.

Practical implications
It could serve as a foundation for autopilots working in non-conventional flight states and aircraft automatic recovery systems.

Originality/value
This paper presents the author’s original approach to aircraft automatic control when high control precision is not the priority and not all flight parameters can be precisely measured.
Introduction of new Picard–S hybrid iteration with application and some results for nonexpansive mappings
Authors: Srivastava Julee 
Published: March 2021

PurposeIn this paper, Picard–S hybrid iterative process is defined, which is a hybrid of Picard and S-iterative process. This new iteration converges faster than all of Picard, Krasnoselskii, Mann, Ishikawa, S-iteration, Picard–Mann hybrid, Picard–Krasnoselskii hybrid and Picard–Ishikawa hybrid iterative processes for contraction mappings and to find the solution of delay differential equation, using this hybrid iteration also proved some results for Picard–S hybrid iterative process for nonexpansive mappings.Design/methodology/approachThis new iteration converges faster than all of Picard, Krasnoselskii, Mann, Ishikawa, S-iteration, Picard–Mann hybrid, Picard–Krasnoselskii hybrid, Picard–Ishikawa hybrid iterative processes for contraction mappings.FindingsShowed the fastest convergence of this new iteration and then other iteration defined in this paper. The author finds the solution of delay differential equation using this hybrid iteration. For new iteration, the author also proved a theorem for nonexpansive mapping.Originality/valueThis new iteration converges faster than all of Picard, Krasnoselskii, Mann, Ishikawa, S-iteration, Picard–Mann hybrid, Picard–Krasnoselskii hybrid, Picard–Ishikawa hybrid iterative processes for contraction mappings and to find the solution of delay differential equation, using this hybrid iteration also proved some results for Picard–S hybrid iterative process for nonexpansive mappings.
Moving theory focus beyond individuals targeted for change: observing project stakeholder interactions
Authors: Roemer Carina , Rundle-Thiele Sharyn , David Patricia 
Published: March 2021

Purpose
Social marketing theories have habituated to a theoretical and methodological focus that is criticised for being myopic and stigmatising. Following recommendations to redirect focus theoretically, the purpose of this paper is to apply an observational methodology to understanding how project stakeholders interact to examine whether consideration of stakeholders can identify factors facilitating or impeding farming practice change.

Design/methodology/approach
More than 48 events involving as many as 150 people including project stakeholder meetings, one-on-one consultations and annual events were observed over more than 100 h by between one and five researchers. Field notes were gathered, and thematic coding focussed on understanding how stakeholders facilitated or impeded practice change.

Findings
Observations identified limited provision of information about the project by on ground project stakeholders to targeted individuals (farmers). On the rare occasions where information sharing was observed, communication was delayed making it difficult for individuals to connect actions with outcomes observed. Participating stakeholders did not freely support delivery of activities needed for individual practice change.

Practical implications
This study indicates the value of wider process and outcome assessment encompassing stakeholders to identify factors impeding and facilitating farming practice change.

Social implications
Approaches that centre attention on individuals fail to acknowledge the inputs, activities and outputs delivered by project stakeholders within a system of change. By redirecting evaluation focus, shared responsibility is gained and stigmatisation of one stakeholder group can be avoided.

Originality/value
This study demonstrates how observations can be used to redirect focus to consider actions and interactions occurring between on ground project stakeholders. A stakeholder evaluation approach extends monitoring and evaluation focus beyond individuals targeted for behaviour change. Implications, limitations and future research directions are outlined.