bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein degradation sets the fraction of active ribosomes at vanishing growth
Authors: Calabrese Ludovico , Grilli Jacopo , Osella Matteo , Kempes Christopher P , Lagomarsino Marco Cosentino , Ciandrini Luca 
Published: March 2021

AbstractGrowing cells adopt common basic strategies to achieve optimal resource allocation under limited resource availability. Our current understanding of such “growth laws” neglects degradation, assuming that it occurs slowly compared to the cell cycle duration. Here we argue that this assumption cannot hold at slow growth, leading to important consequences. We propose a simple framework showing that at slow growth protein degradation is balanced by a fraction of “maintenance” ribosomes. Consequently, active ribosomes do not drop to zero at vanishing growth, but as growth rate diminishes, an increasing fraction of active ribosomes performs maintenance. Through a detailed analysis of compiled data, we show that the predictions of this model agree with data fromE. coliandS. cerevisiae. Intriguingly, we also find that protein degradation increases at slow growth, which we interpret as a consequence of active waste management and/or recycling. Our results highlight protein turnover as an underrated factor for our understanding of growth laws across kingdoms.Author summaryThe idea that simple quantitative relationships relate cell physiology to cellular composition dates back to the 1950s, but the recent years saw a leap in our understanding of such “growth laws”, with relevant implications regarding the interdependence between growth, metabolism and biochemical networks. However, recent works on nutrient-limited growth mainly focused on laboratory conditions that are favourable to growth. Thus, our current mathematical understanding of the growth laws neglects protein degradation, under the argument that it occurs slowly compared to the timescale of the cell cycle. Instead, at slow growth the timescales of mass loss from protein degradation and dilution become comparable. In this work, we propose that protein degradation shapes the quantitative relationships between ribosome allocation and growth rate, and determines a fraction of ribosomes that do not contribute to growth and need to remain active to balance degradation.
Integrating diverse data sources to predict disease risk in dairy cattle
Authors: Lasser Jana , Matzhold Caspar , Egger-Danner Christa , Fuerst-Waltl Birgit , Steininger Franz , Wittek Thomas , Klimek Peter 
Published: March 2021

ABSTRACTLivestock farming is currently undergoing a digital revolution and becoming increasingly data-driven. Yet, such data often reside in disconnected silos making it impossible to leverage their full potential to improve animal well-being. Here, we introduce a precision medicine approach, bringing together information streams from a variety of life domains of dairy cattle to predict eight common and economically important diseases. Dairy cows are part of a highly industrialised environment. The animals and their surroundings are closely monitored and environmental, behavioural and physiological observations are readily accessible yet seldomly integrated. We use random forest classifiers trained on data from 5,828 animals in 166 herds in Austria to predict occurrences of lameness, acute and chronic mastitis, anoestrus, ovarian cysts, metritis, ketosis (hyperketonemia) and periparturient hypocalcemia (milk fever). To assess the importance of specific cattle life domains and individual features for these predictions, we use multivariate logistic regression and feature permutation approaches. We show that disease in dairy cattle is a product of the complex interplay between a multitude of life domains such as housing, nutrition or climate, and identify a range of features that were previously not associated with increased disease risk. For example, we can predict anoestrus with high sensitivity and specificity (F1=0.72) and find that housing, feed and husbandry variables such as barn design and time on pasture are most predictive of this disease. We also find previously unknown associations of features with disease risk, for example humid conditions, which significantly decrease the odds for ketosis. Our findings pave the way towards data-driven point-of-care interventions and demonstrate the added value of integrating all available data in the dairy industry to improve animal well-being and reduce disease risk.
Spatiotemporal Control of Actomyosin Contractility by MRCKβ Signaling Drives Phagocytosis
Authors: Zihni Ceniz , Georgiadis Anastasios , Ramsden Conor M. , Sanchez-Heras Elena , Nommiste Britta , Semenyuk Olha , Bainbridge James W.B. , Coffey Peter J. , Smith Alexander J. , Ali Robin R. , Balda Maria S. , Matter Karl 
Published: March 2021

SUMMARYPhagocytosis requires myosin-generated contractile force to regulate actin dynamics. However, little is known about the molecular mechanisms that guide this complex morphodynamic process. Here we show that particle binding to Mer Tyrosine Kinase (MerTK), a widely expressed phagocytic receptor, stimulates phosphorylation of the Cdc42 GEF Dbl3 in the retinal pigment epithelium (RPE), triggering activation of MRCKβ and its co-effector N-WASP that cooperate to deform the membrane into cups. Continued MRCKβ activity then drives recruitment of a mechanosensing bridge enabling transmission of the cytoskeletal force required for cup closure and particle internalization. MRCKβ is also required for Fc receptor-mediated phagocytosis by macrophages.In vivo, MRCKβ is essential for RPE phagocytosis of photoreceptor debris and, hence, retinal integrity. MerTK-independent activation of MRCKβ signaling by a phosphomimetic Dbl3 mutant rescues phagocytosis in retinitis pigmentosa RPE cells lacking functional MerTK. Thus, conserved MRCKβ signaling controls spatiotemporal regulation of actomyosin contractility to guide actomyosin dynamics-driven phagocytosis and represents the principle phagocytic effector pathway downstream of MerTK.
Strength of interactions in the Notch gene regulatory network determines patterning and fate in the notochord
Authors: Sánchez-Iranzo Héctor , Halavatyi Aliaksandr , Diz-Muñoz Alba 
Published: March 2021

ABSTRACTDevelopment of multicellular organisms requires the generation of gene expression patterns that determines cell fate and organ shape. Groups of genetic interactions known as Gene Regulatory Networks (GRNs) play a key role in the generation of such patterns. However, how the topology and parameters of GRNs determine patterningin vivoremains unclear due to the complexity of most experimental systems. To address this, we use the zebrafish notochord, an organ where coin-shaped precursor cells are initially arranged in a simple unidimensional geometry. These cells then differentiate into vacuolated and sheath cells. Using newly developed transgenic tools together with in vivo imaging, we identifyjag1aandher6/her9as the main components of a Notch GRN that generates a lateral inhibition pattern and determines cell fate. Making use of this experimental system and mathematical modeling we show that lateral inhibition patterning requires that ligand-receptor interactions are stronger within the same cell than in neighboring cells. Altogether, we establish the zebrafish notochord as an experimental system to study pattern generation, and identify and characterize how the properties of GRNs determine self-organization of gene patterning and cell fate.
Dual TCR-alpha expression on MAIT cells as a potential confounder of TCR interpretation
Authors: Suliman Sara , Kjer-Nielsen Lars , Iwany Sarah K. , Tamara Kattya Lopez , Loh Liyen , Grzelak Ludivine , Kedzierska Katherine , Ocampo Tonatiuh A. , Corbett Alexandra J. , McCluskey James , Rossjohn Jamie , León Segundo R , Calderon Roger , Garcia Leonid Lecca , Murray Megan B. , Moody D. Branch , Van Rhijn Ildiko 
Published: March 2021

AbstractMucosal-associated invariant T (MAIT) cells are innate-like T cells that are highly abundant in human blood and tissues. Most MAIT cells have an invariant T cell receptor (TCR) α chain that uses TRAV1-2 joined to TRAJ33/20/12 and recognize metabolites from bacterial riboflavin synthesis bound to the antigen-presenting molecule, MR1. Recently, our attempts to identify alternative MR1-presented antigens led to the discovery of rare MR1-restricted T cells with non-TRAV1-2 TCRs. Because altered antigen specificity is likely to lead to altered affinity for the most potent known antigen, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), we performed bulk TCRα and β chain sequencing, and single cell-based paired TCR sequencing, on T cells that bound the MR1-5-OP-RU tetramer, but with differing intensities. Bulk sequencing showed that use of V genes other than TRAV1-2 was enriched among MR1-5-OP-RU tetramerlowcells. Whereas we initially interpreted these as diverse MR1-restricted TCRs, single cell TCR sequencing revealed that cells expressing atypical TCRα chains also co-expressed an invariant MAIT TCRα chain. Transfection of each non-TRAV1-2 TCRα chain with the TCRβ chain from the same cell demonstrated that the non-TRAV1-2 TCR did not bind the MR1-5-OP-RU tetramer. Thus, dual TCRα chain expression in human T cells and competition for the endogenous β chain explains the existence of some MR1-5-OP-RU tetramerlowT cells. The discovery of simultaneous expression of canonical and non-canonical TCRs on the same T cell means that claims of roles for non-TRAV1-2 TCR in MR1 response must be validated by TCR transfer-based confirmation of antigen specificity.
Thermal Fogging with Disinfectant Didecyl Dimethyl Ammonium Bromide Effectively Kills A Coronavirus, An Influenza Virus and Two Indicator Bacteria in Subzero Cold-Chain Environment
Authors: Hu Qiaoyun , Ma Pei , Hong Junyi , Wang Yulong , Huang Dong , Tan Yadi , Yu Zhengjun 
Published: March 2021

AbstractBackgroundThe origin of several local COVID-19 outbreaks in China in 2020 were confirmed to be frozen food or packages contaminated with SARS-CoV-2, revealing the lack of effective disinfection measures in the frozen food chain.ObjectiveTo evaluate the disinfection efficacy at −20°C of a recently marketed thermal fogging disinfection product, with disinfectant-antifreeze combination being didecyl dimethyl ammonium bromide (DDAB) - propylene glycol (PPG).MethodCarriers with porcine epidemic diarrhea virus (PEDV) YN1, a coronavirus, and a swine influenza virus H1N1 (SIV-H1N1), and three indicator bacteria,E. coli, S. aureus,andB. subtilisendospores, were respectively placed in a −20°C freezer warehouse with or without DDAB-PPG fogging and activities of the microorganisms were tested.ResultsAt −20°C, DDAB-PPG fogging, which fully settles in 3.5−4.5 hours, fully inactivated PEDV of 10−3.5TCID50/0.1ml and SIV-H1N1 of 26hemagglutination titer within 15-30 min, and inactivatedS. aureusandE. colivegetative cells (106/ml) within 15 or 60 min, respectively, but had little effect onB. subtilisspores. The bactericidal effect lasted at least 3 hours for bacteria on carrier plates and for 6 hours for airborne bacteria.ConclusionsA practical subzero temperature disinfection technology was confirmed its efficacy in killing enveloped viruses and vegetative bacteria. It would help to meet the urgent public health need of environmental disinfection in frozen food logistics against pandemic and other potential pathogens and to enhance national and international biosecurity.HighlightsFirst report of efficacy of disinfectant didecyl dimethyl ammonium bromide (DDAB) at subzero temperaturesThe customized thermal fogging machine makes fine droplets of DDAB-propylene glycol (PPG) fog which can suspend for ~4 hours at −20°CDDAB-PPG thermal fogging at −20°C effectively inactivated a coronavirus and an influenza virusDDAB-PPG thermal fogging at −20°C for effectively killedS. aureusandE. coliDDAB-PPG thermal fogging at −20°C inactivated airborne microorganism for up to 6 h
Genomic Alterations and Possible Druggable Mutations in Carcinoma of Unknown Primary (CUP)
Authors: Aboulkheyr Es Hamidreza , Mahdizadeh Hamid , Hedayati Asl Amir Abbas , Totonchi Mehdi 
Published: March 2021

SummaryCarcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is an only state-of-art treatment option for the CUP patient. Employing molecular profiling of the tumour, particularly mutation detection, offers a new treatment for CUP in a personalized fashion. Here, we analyzed mutation and copy number alterations profile of 1,709 CUP samples deposited in GENIE cohort and explored potential druggable mutations. We identified 52 significant mutated genes (SMG) among CUP samples, of which 13 (25%) of SMG were potentially targetable with drugs reproved for the know primary tumour or undergoing clinical trials. The most variants detected wereTP53(43%),KRAS(19.90%),KMT2D(12.60%), andCDKN2A(10.30%). Additionally, the presence of similar variants ofTERTpromoter in CUP compared to NSCLC samples suggests these mutations may serve as a diagnostic marker for identifying the primary tumour in CUP. Taken together, analyzing mutation profiling of the CUP tumours may open a new way of identifying druggable targets and consequently administrating appropriate treatment in a personalized manner.
Diversity and metagenome analysis of a hydrocarbon-degrading bacterial consortium from asphalt lakes located in Wietze, Germany
Authors: Eze Michael O. , Hose Grant C. , George Simon C. , Daniel Rolf 
Published: March 2021

AbstractThe pollution of terrestrial and aquatic environments by petroleum contaminants, especially diesel fuel, is a persistent environmental threat requiring cost-effective and environmentally sensitive remediation approaches. Bioremediation is one such approach, but is dependent on the availability of microorganisms with the necessary metabolic abilities and environmental adaptability. The aim of this study was to examine the microbial community in a petroleum contaminated site, and isolate organisms potentially able to degrade hydrocarbons. Through successive enrichment of soil microorganisms from samples of an historic petroleum contaminated site in Wietze, Germany, we isolated a bacterial consortium using diesel fuel hydrocarbons as sole carbon and energy source. The 16S rRNA gene analysis revealed the dominance ofAlphaproteobacteria. We further reconstructed a total of 18 genomes from both the original soil sample and the isolated consortium. The analysis of both the metagenome of the consortium and the reconstructed metagenome-assembled genomes show that the most abundant bacterial genus in the consortium,Acidocella, possess many of the genes required for the degradation of diesel fuel aromatic hydrocarbons, which are often the most toxic component. This can explain why this genus proliferated in all the enrichment cultures. Therefore, this study reveals that the microbial consortium isolated in this study and its dominant genus,Acidocella, could potentially serve as an effective inoculum for the bioremediation of sites polluted with diesel fuel or other organic contaminants.
A robust, semi-automated approach for counting cementum increments imaged with X-ray computed tomography
Authors: Newham Elis , Gill Pamela G. , Brown Kate Robson , Gostling Neil J. , Corfe Ian J. , Schneider Philipp 
Published: March 2021

AbstractCementum, the tissue attaching mammal tooth roots to the periodontal ligament, grows appositionally throughout life, displaying a series of circum-annual incremental features. These have been studied for decades as a direct record of chronological lifespan. The majority of previous studies on cementum have used traditional thin-section histological methods to image and analyse increments. However, several caveats have been raised in terms of studying cementum increments in thin-sections. Firstly, the limited number of thin-sections and the two-dimensional perspective they impart provide an incomplete interpretation of cementum structure, and studies often struggle or fail to overcome complications in increment patterns that complicate or inhibit increment counting. Increments have been repeatedly shown to both split and coalesce, creating accessory increments that can bias increment counts. Secondly, identification and counting of cementum increments using human vision is subjective, and it has led to inaccurate readings in several experiments studying individuals of known age. Here, we have attempted to optimise a recently introduced imaging modality for cementum imaging; X-ray propagation-based phase-contrast imaging (PPCI). X-ray PPCI was performed for a sample of rhesus macaque (Macaca mulatta) lower first molars (n=10) from a laboratory population of known age. A new method for semi-automatic incrementcounting was then integrated into a purpose-built software package for studying cementum increments. Comparison with data from conventional cementochronology, based on histological examination of tissue sections, confirmed that X-ray PPCI reliably records cementum increments. Validation of the increment counting algorithm suggests that it is robust and provides accurate estimates of increment counts. In summary, we show that our new increment counting method has the potential to overcome caveats of conventional cementochronology approaches, when used to analyse 3D images provided by X-ray PPCI.
Systematics and phylogeography of the Brazilian Atlantic Forest endemic harvestmenNeosadocusMello-Leitão, 1926 (Arachnida: Opiliones: Gonyleptidae)
Authors: Castro-Pereira Daniel , Peres Elen A. , Pinto-da-Rocha Ricardo 
Published: March 2021

AbstractNeosadocusharvestmen are endemic to the Southern Brazilian Atlantic Forest. Although they are conspicuous and display great morphological variation, their evolutionary history and the biogeographical events underlying their diversification and distribution are still unknown. This contribution aboutNeosadocusincludes the following: a taxonomic revision; a molecular phylogenetic analysis using mitochondrial and nuclear markers; an investigation of the genetic structure and species’ diversity in a phylogeographical framework. Our results show thatNeosadocusis a monophyletic group and comprises four species:N. bufo,N. maximus,N. robustusandN. misandrus(which we did not find on fieldwork and only studied the female holotype). There is astonishing male polymorphism inN. robustus, mostly related to reproductive strategies. The following synonymies have resulted from this work:Bunoweyhia variabilisMello-Leitão, 1935 =Neosadocus bufo(Mello-Leitão, 1926); andBunoweyhia minorMello-Leitão, 1935 =Neosadocus maximus(Giltay, 1928). Most divergences occurred during the Miocene, a geological epoch marked by intense orogenic and climatic events in the Brazilian Atlantic Forest. Intraspecific analyses indicate strong population structure, a pattern congruent with the general behavior and physiological constraints of Neotropical harvestmen.
FPM app: an open-source application for simple and intuitive Fourier ptychographic reconstruction
Authors: Rogalski Mikołaj , Zdańkowski Piotr , Trusiak Maciej 
Published: March 2021

AbstractSummaryFourier ptychographic microscopy (FPM) is a computational microscopy technique that enables large field of view and high-resolution microscopic imaging of biological samples. However, the FPM does not yet have an adequately capable open-source software. In order to fill this gap we are presenting novel, simple, universal, semi-automatic and highly intuitive graphical user interface (GUI) open-source application called theFPM appenabling wide-scale robust FPM reconstruction. Apart from implementing the FPM in accessible GUI app, we also made several improvements in the FPM image reconstruction process itself, making the FPM more automatic, noise-robust and faster.Availability and ImplementationFPM appwas implemented in MATLAB and all MATLAB codes along with standalone executable version of theFPM appand the online documentation are freely accessible athttps://github.com/MRogalski96/FPM-app. Our exemplary FPM datasets may be downloaded athttps://bit.ly/2MxNpGb.
Tissue flow through pores: a computational study
Authors: Kempf Felix , Goychuk Andriy , Frey Erwin 
Published: March 2021

AbstractCell migration is of major importance for the understanding of phenomena such as morphogenesis, cancer metastasis, or wound healing. In many of these situations cells are under external confinement. In this work we show by means of computer simulations with a Cellular Potts Model (CPM) that the presence of a bottleneck in an otherwise straight channel has a major influence on the internal organisation of an invading cellular monolayer and the motion of individual cells therein. Comparable to a glass or viscoelastic material, the cell sheet is found to exhibit features of both classical solids and classical fluids. The local ordering on average corresponds to a regular hexagonal lattice, while the relative motion of cells is unbounded. Compared to an unconstricted channel, we observe that a bottleneck perturbs the formation of regular hexagonal arrangements in the epithelial sheet and leads to pile-ups and backflow of cells near the entrance to the constriction, which also affects the overall invasion speed. The scale of these various phenomena depends on the dimensions of the different channel parts, as well as the shape of the funnel domain that connects wider to narrower regions.
CG2AT2: An Enhanced Fragment-based approach for Serial Multi-scale Molecular Dynamics simulations
Authors: Vickery Owen N. , Stansfeld Phillip J. 
Published: March 2021

AbstractCoarse-grained molecular dynamics provides a means for simulating the assembly and interactions of macromolecular complexes at a reduced level of representation, thereby allowing both longer timescale and larger sized simulations. Here, we describe an enhanced fragment-based protocol for converting macromolecular complexes from coarse-grained to atomistic resolution, for further refinement and analysis. While the focus is upon systems that comprise an integral membrane protein embedded in a phospholipid bilayer, the technique is also suitable for e.g. membrane-anchored and soluble protein/nucleotide complexes. Overall, this provides a method for generating an accurate and well equilibrated atomic-level description of a macromolecular complex. The approach is evaluated using a diverse test set of eleven system configurations of vary size and complexity. Simulations are assessed in terms of protein stereochemistry, conformational drift, lipid/protein interactions, and lipid dynamics.
Lipid membranes modulate the activity of RNA through sequence-dependent interactions
Authors: Czerniak Tomasz , Saenz James P 
Published: March 2021

AbstractRNA is a ubiquitous biomolecule that can serve as both catalyst and information carrier. Understanding how RNA bioactivity is controlled is crucial for elucidating its physiological roles and potential applications in synthetic biology. Here we show that lipid membranes can act as RNA organization platforms, introducing a novel mechanism for ribo-regulation. The activity of R3C ribozyme can be modified by the presence of lipid membranes, with direct RNA-lipid interactions dependent on RNA nucleotide content, base pairing and length. In particular, the presence of guanine in short RNAs is crucial for RNA-lipid interactions, and G-quadruplex formation further promotes lipid binding. Lastly, by artificially modifying the R3C substrate sequence to enhance membrane binding we generated a lipid-sensitive ribozyme reaction with riboswitch-like behavior. These findings introduce RNA-lipid interactions as a tool for developing synthetic riboswitches and novel RNA-based lipid biosensors, and bear significant implications for RNA World scenarios for the origin of life.