bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical model of efficient phagocytosis driven by curved membrane proteins and active cytoskeleton forces
Authors: Sadhu Raj Kumar , Barger Sarah R , Penič Samo , Iglič Aleš , Krendel Mira , Gauthier Nils C , Gov Nir S 
Published: January 2022

Phagocytosis is the process of engulfment and internalization of comparatively large particles by the cell, that plays a central role in the functioning of our immune system. We study the process of phagocytosis by considering a simplified coarse grained model of a three-dimensional vesicle, having uniform adhesion interaction with a rigid particle, in the presence of curved membrane proteins and active cytoskeletal forces. Complete engulfment is achieved when the bending energy cost of the vesicle is balanced by the gain in the adhesion energy. The presence of curved (convex) proteins reduces the bending energy cost by self-organizing with higher density at the highly curved leading edge of the engulfing membrane, which forms the circular rim of the phagocytic cup that wraps around the particle. This allows the engulfment to occur at much smaller adhesion strength. When the curved proteins exert outwards protrusive forces, representing actin polymerization, at the leading edge, we find that engulfment is achieved more quickly and at lower protein density. We consider spherical as well as non-spherical particles, and find that non-spherical particles are more difficult to engulf in comparison to the spherical particles of the same surface area. For non-spherical particles, the engulfment time crucially depends upon the initial orientation of the particles with respect to the vesicle. Our model offers a mechanism for the spontaneous self-organization of the actin cytoskeleton at the phagocytic cup, in good agreement with recent high-resolution experimental observations.Significance StatementPhagocytosis is an important process that plays a central role in our immune system, and also during nutrient uptake, drug delivery and pathogen invasion. Despite its biological importance, it is still not understood how the actin cytoskeleton is coordinated spatio-temporally during the phagocytosis process. We present a simple model that explains the dynamics and self-organization of the membrane and the actin cytoskeleton during the engulfment process, based on curved membrane activators of actin polymerization.
Comparative whole plastome and low copy number phylogenetics of the core Saccharinae and Sorghinae
Authors: Evans Dyfed Lloyd , Hughes Ben , Joshi Shailesh Vinay 
Published: January 2022

AbstractDespite over 60 years’ worth of taxonomic efforts, the relationships between sugarcane (Saccharum hybrid cultivars), Sorghum and their closest evolutionary relatives remain largely unresolved. Even relationships between generally accepted genera such as Miscanthus and Saccharum have not been examined in any large-scale molecular detail. Genera such as Erianthus, Miscanthidium and Narenga pose even greater taxonomic contention. Erianthus is not monophyletic and Erianthus sect. Ripidium (Valdés and Scholz 2006, Lloyd Evans et al. 2019a; Welker et al. 2019) represents a distinct and separate genus, Tripidium Scholz. Miscanthidium is placed within Miscanthus by many workers, whilst the New World Erianthus species and Narenga are currently placed within Saccharum. As these species represent a significant portion of the gene pool that sugarcane breeders use for introgression into sugarcane, their taxonomic placement and relationships to Saccharum are of significant economic import. Erianthus species from the Americas have not been significantly employed in sugarcane breeding and may represent an untapped genetic resource. In an attempt to resolve the taxonomic relationships of these genera, we have assembled three novel chloroplasts, from Miscanthidium capense, Miscanthidium junceum and Narenga porphyrocoma (this latter assembled from transcriptomic and long read data). In parallel, five low copy number loci have been assembled from species within Saccharum, Miscanthus, Sarga and Sorghum. Phylogenetic analyses were performed using both low copy number genes and whole chloroplasts. The phylogenetic results were compared with karyotype data to circumscribe the genera most closely related to sugarcane. We reveal that genera Miscanthus and Saccharum are monophyletic and have never undergone polyploidization outside their own genera. Genera Erianthus, Miscanthidium and Narenga are allopolyploids, which excludes them from being members of Saccharum and Miscanthus. Moreover, all three of these genera have divergent evolutionary histories. We therefore support the use of the genera Miscanthus, Miscanthidium, Erianthus (for the New World Species) and Narenga for those species and genera most closely allied to Saccharum. Our data demonstrate that all these genera should be excluded from Saccharum sensu lato.
B1 SINE-binding ZFP266 impedes reprogramming through suppression of chromatin opening mediated by pioneering factors
Authors: Kaemena Daniel F , Yoshihara Masahito , Ashmore James , Beniazza Meryam , Zhao Suling , Bertenstam Mårten , Olariu Victor , Katayama Shintaro , Okita Keisuke , Tomlinson Simon R , Yusa Kosuke , Kaji Keisuke 
Published: January 2022

AbstractInduced pluripotent stem cell reprogramming is inherently inefficient and understanding the molecular mechanisms underlying this inefficiency holds the key to successfully control cellular identity. Here, we report 16 novel reprogramming roadblock genes identified by CRISPR/Cas9-mediated genome-wide knockout (KO) screening. Of these, depletion of the predicted KRAB zinc finger protein (KRAB-ZFP) Zfp266 strongly and consistently enhanced iPSC generation in several iPSC reprogramming settings, emerging as the most robust roadblock. Further analyses revealed that ZFP266 binds Short Interspersed Nuclear Elements (SINEs) adjacent to binding sites of pioneering factors, OCT4 (POU5F1), SOX2 and KLF4, and impedes chromatin opening. Replacing the KRAB co-suppressor with a co-activator domain converted ZFP266 from a reprogramming inhibitor to a potent reprogramming facilitator. This work proposes SINE-KRAB-ZFP interaction to be a critical regulator of chromatin accessibility at enhancers for efficient cellular identity changes and also serves as a resource to further illuminate molecular mechanisms hindering reprogramming.
PDBspheres - a method for finding 3D similarities in local regions in proteins
Authors: Zemla Adam T. , Allen Jonathan E. , Kirshner Dan , Lightstone Felice C. 
Published: January 2022

ABSTRACTWe present a structure-based method for finding and evaluating structural similarities in protein regions relevant to ligand binding. PDBspheres comprises an exhaustive library of protein structure regions (“spheres”) adjacent to complexed ligands derived from the Protein Data Bank (PDB), along with methods to find and evaluate structural matches between a protein of interest and spheres in the library. PDBspheres uses the LGA structure alignment algorithm as the main engine for detecting structure similarities between the protein of interest and template spheres from the library, which currently contains more than 2 million spheres. To assess confidence in structural matches an all-atom-based similarity metric takes sidechain placement into account. Here, we describe the PDBspheres method, demonstrate its ability to detect and characterize binding sites in protein structures, show how PDBspheres - a strictly structure-based method - performs on a curated dataset of 2,528 ligand-bound and ligand-free crystal structures, and use PDBspheres to cluster pockets and assess structural similarities among protein binding sites of 4,876 structures in the “refined set” of the PDBbind 2019 dataset.
PACpAInt: a deep learning approach to identify molecular subtypes of pancreatic adenocarcinoma on histology slides
Authors: Saillard C. , Delecourt F. , Schmauch B. , Moindrot O. , Svrcek M. , Bardier-Dupas A. , Emile J-F. , Ayadi M. , Rebours V. , de Mestier L. , Hammel P. , Neuzillet C. , Bachet J-B. , Iovanna J. , Dusetti N. , Blum Y. , Richard M. , Kermezli Y. , Paradis V. , Zaslavskiy M. , Courtiol P. , Kamoun A. , Nicolle R. , Cros J. 
Published: January 2022

AbstractPancreatic ductal adenocarcinoma (PAC) is a highly heterogeneous and plastic tumor with different transcriptomic molecular subtypes that hold great prognostic and theranostic values. We developed PACpAInt, a multistep approach using deep learning models to determine tumor cell type and their molecular phenotype on routine histological preparation at a resolution enabling to decipher complete intratumor heterogeneity on a massive scale never achieved before. PACpAInt effectively identified molecular subtypes at the slide level in three validation cohorts and had an independent prognostic value. It identified an interslide heterogeneity within a case in 39% of tumors that impacted survival. Diving at the cell level, PACpAInt identified “pure” classical and basal-like main subtypes as well as an intermediary phenotype and hybrid tumors that co-carried both classical and basal-like phenotypes. These novel artificial intelligence-based subtypes, together with the proportion of basal-like cells within a tumor had a strong prognostic impact.
Deterministic approximation for population dynamics in the presence of advantageous mutants
Authors: Rodriguez-Brenes Ignacio A. , Wodarz Dominik , Komarova Natalia L. 
Published: January 2022

AbstractSpatial stochastic simulations of evolutionary processes are computationally expensive. Here, based on spatially explicit decoupling approximations (SEDA) introduced in [1], we derive a deterministic approximation to a spatial stochastic birth-death process in the presence of two types: the less advantageous resident type and a more advantageous mutant. At the core of this technique are two essential steps: (1) a system of ODEs that approximate spatial interactions among neighboring individuals must be solved; (2) the time-variable has to be rescaled with a factor (called “α”) that depends on the kinetic parameters of the wild type and mutant individuals. An explicit formula for α is derived, which is a power law of division and death rates of the two types. The method is relatively fast and provides excellent time-series agreement with the stochastic simulation results for the spatial agent-based model. The methodology can be used to describe hard selective sweep events, including the expansion of driver mutations in carcinogenesis, bacterial evolution, and aspects of resistance dynamics.
Automated Landmarking via Multiple Templates
Authors: Zhang Chi , Porto Arthur , Rolfe Sara , Kocatulum Altan , Maga A. Murat 
Published: January 2022

AbstractGeometric morphometrics based on landmark data has been increasingly used in biomedical and biological research for quantifying complex phenotypes. However, manual landmarking can be laborious and subject to intra and interobserver errors. This has motivated the development of automated landmarking methods. We have recently introduced ALPACA (Automated Landmarking through Point Cloud Alignment and Correspondence), a fast method to automatically annotate landmarks via the use of a landmark template as a part of the SlicerMorph toolkit. Yet, using a single template may not consistently perform well for large study samples, especially when the sample consists of specimens with highly variable morphology, as it is common in evolutionary studies. In this study, we introduce a variation on our ALPACA pipeline that supports multiple specimen templates, which we call MALPACA. We show that MALPACA outperforms ALPACA consistently by testing on two different datasets. We also introduce a method of choosing the templates that can be used in conjunction with MALPACA, when no prior information is available. This K-means method uses an approximation of the total morphological variation in the dataset to suggest samples within the population to be used as landmark templates. While we advise investigators to pay careful attention to the template selection process in any of the template-based automated landmarking approaches, our analyses show that the introduced K-means based method of templates selection is better than randomly choosing the templates. In summary, MALPACA can accommodate larger morphological disparity commonly found in evolutionary studies with performance comparable to human observer.
Apical and basal auxin sources pattern shoot branching in a moss
Authors: Thelander Mattias , Landberg Katarina , Muller Arthur , Cloarec Gladys , Cunniffe Nik , Huguet Stéphanie , Soubigou-Taconnat Ludivine , Brunaud Véronique , Coudert Yoan 
Published: January 2022

AbstractShoot branching mechanisms where branches arise in association with leaves – referred to as lateral or axillary branching – evolved by convergence in the sporophyte of vascular plants and the gametophyte of bryophytes, and accompanied independent events of plant architectural diversification1. Previously, we showed that three hormonal cues, including auxin, have been recruited independently to co-ordinate branch patterning in flowering plant leafy shoots and moss gametophores (Coudert, Palubicki et al., 2015)2–4. Moreover, auxin-mediated apical dominance, which relies on local auxin production, has been proposed as a unifying molecular regulatory mechanism of branch development across land plants5. Whilst our previous work in the moss Physcomitrium patens has gathered indirect evidence supporting the notion that auxin synthesized in gametophore apices regulates branch formation at a distance2, direct genetic evidence for a role of auxin biosynthesis in gametophore branching control is still lacking. Here, we show that gametophore apex decapitation promotes branch emergence through massive and rapid transcriptional reprogramming of auxin-responsive genes and altering auxin biosynthesis gene activity. Specifically, we identify a subset of P. patens TRYPTOPHAN AMINO-TRANSFERASE (TAR) and YUCCA FLAVIN MONOOXYGENASE-LIKE (YUC) auxin biosynthesis genes expressed in apical and basal regions of the gametophore, and show that they are essential for branch initiation and outgrowth control. Our results demonstrate that local auxin biosynthesis coordinates branch patterning in moss and thus constitutes a shared and ancient feature of shoot architecture control in land plants.
The formation of a fuzzy complex in the negative arm regulates the robustness of the circadian clock
Authors: Jankowski Meaghan S. , Griffith Daniel , Shastry Divya G. , Pelham Jacqueline F. , Ginell Garrett M. , Thomas Joshua , Karande Pankaj , Holehouse Alex S. , Hurley Jennifer M. 
Published: January 2022

SummaryThe circadian clock times cellular processes to the day/night cycle via a Transcription-Translation negative Feedback Loop (TTFL). However, a mechanistic understanding of the negative arm in both the timing of the TTFL and its control of output is lacking. We posited that the formation of negative-arm protein complexes was fundamental to clock regulation stemming from the negative arm. Using a modified peptide microarray approach termed Linear motif discovery using rational design (LOCATE), we characterized the interaction of the disordered negative-arm clock protein FREQUENCY to its partner protein FREQUENCY-Interacting RNA helicase. LOCATE identified a specific Short Linear Motif (SLiM) and interaction “hotspot” as well as positively charged “islands” that mediate electrostatic interactions, suggesting a model where negative arm proteins form a “fuzzy” complex essential for clock timing and robustness. Further analysis revealed that the positively charged islands were an evolutionarily conserved feature in higher eukaryotes and contributed to proper clock function.
Variable Shh and Fgf8 positioning in regenerating axolotl limb guarantees consistent limb morphogenesis in different limb sizes
Authors: Furukawa Saya , Yamamoto Sakiya , Kashimoto Rena , Morishita Yoshihiro , Satoh Akira 
Published: January 2022

AbstractLimb regeneration in Ambystoma mexicanum occurs in various size fields and can recreate consistent limb morphology. The mechanism that supports such stable limb morphogenesis regardless of size is unknown. Sonic hedgehog (SHH) and fibroblasts growth factor 8 (FGF8) play important roles in anteroposterior limb patterning, similar to other tetrapods. Focusing on these two factors, we investigated the detailed expression pattern and function of Shh and Fgf8 in various blastema sizes in axolotl limb regeneration. We measured and functionally analyzed the expression domains of Shh and Fgf8 in regenerating limb blastema of various sizes, and found that, although the position and size of the Shh+ and Fgf8+ domains varied depending on the size of the blastema, the secretion of SHH was maintained at a relatively fixed working distance, regardless of blastema size. This stable secretory distance of SHH resulted in the formation of an active proliferative zone (aPZ) in the vicinity of SHH, regardless of blastema size. The aPZ was under the mitogenic influence of SHH and FGF8, resulting in high cell density in the aPZ. We also examined the impact of the aPZ on digit formation. We found that the first digit formation occurs in the aPZ. Next, the aPZ gradually shifts posteriorly as digits develop, which contributes to new digit formation at the site of the shifted aPZ. We also found that the exogenously formed aPZ caused extra digit formation even after the completion of autopod morphogenesis. Our findings suggest that the variable Shh-Fgf8 positioning in various blastema sizes causes various positioning of the aPZ, and that the aPZ leads to digit formation. The mechanism we propose here accounts for stable digit morphogenesis regardless of blastema sizes and urodele-specific digit formation.One-Sentence SummaryA unique SHH-FGF8 spatial interaction compensates for robust limb morphogenesis in various limb sizes.
Personal Resilience, Social Support, and Organizational Support Impact Burnout among Nurses During COVID-19
Authors: Daghash Hanan 
Published: January 2022

AbstractBackgroundNurses have been under heavy workloads since the outbreak of COVID-19 and are at a high risk of infection, leading to a high level of psychosocial risk. This can adversely affect nurses both psychologically and physically. Burnout is caused by prolonged stress during work. In the nursing profession, burnout is common, potentially affecting the well-being of nurses and their productivity. The identification of factors that may contribute to maintaining mental health and reducing burnout among frontline nurses during a pandemic is essential.PurposeThe purpose of this study was to explore how personal resilience, social support, and organizational support impact burnout among frontline staff nurses.MethodsThis study involved 129 registered nurses from a COVID-19 designated hospital using four standardized scales.ResultsThe mean age of the respondents was 29.46 years (standard deviation = 4.89). The mean number of years respondents worked in this organization was 5.60 years and the nursing profession was 4.16 years. Most of the respondents were female and held a bachelor’s degree in nursing. Multiple regression analysis was performed to predict burnout. Burnout was statistically significantly predicted by the multiple regression model (R2 = .420, F (3, 125) = 10.941, p < .0001; adjusted R2 = .406). Personal resilience, social support, and organizational support added statistically significantly to the prediction of burnout (p < .05).ConclusionFindings from multiple regression analysis showed that nurses with low resilience and those who perceived inadequate social and organizational support had a higher risk of reporting more burnout. As a result of a bivariate analysis, there was no significant correlation between nurse variables and burnout level, except for age, which was negatively correlated with burnout level. Accordingly, young nurses tend to experience burnout, and nurse directors and managers must address this problem.
Spatial scales of competition and a growth-motility tradeoff interact to determine bacterial coexistence
Authors: Kuhn Thierry , Mamin Marine , Bindschedler Saskia , Bshary Redouan , Estoppey Aislinn , Gonzalez Diego , Palmieri Fabio , Junier Pilar , Richter Xiang-Yi Li 
Published: January 2022

1.AbstractThe coexistence of competing species is a long-lasting puzzle in evolutionary ecology research. Despite abundant experimental evidence showing that the opportunity for coexistence decreases as niche overlap increases between species, bacterial species and strains competing for the same resources are commonly found across diverse spatially heterogeneous habitats. We thus hypothesized that the spatial scale of competition may play a key role in determining bacterial coexistence, and interact with other mechanisms that promote coexistence, including a growth-motility tradeoff. To test this hypothesis, we let twoPseudomonas putidastrains compete at local and regional scales by inoculating them either in a mixed droplet or in separate droplets in the same Petri dish, respectively. We also created conditions that allow the bacterial strains to disperse across abiotic or fungal hyphae networks. We found that competition at the local scale led to competitive exclusion while regional competition promoted coexistence. When competing in the presence of dispersal networks, the growth-motility tradeoff promoted coexistence only when the strains were inoculated in separate droplets. Our results provide a mechanism by which existing laboratory data suggesting competitive exclusion at a local scale is reconciled with the widespread coexistence of competing bacterial strains in complex natural environments with dispersal.
Cryo-EM structure of human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand binding specificity
Authors: Heo Yunseok , Yoon Eojin , Jeon Ye-Eun , Yun Ji-Hye , Ishimoto Naito , Woo Hyeonuk , Park Sam-Yong , Song Ji-Joon , Lee Weontae 
Published: January 2022

AbstractSomatostatin is a peptide hormone regulating endocrine systems through binding to G-protein-coupled somatostatin receptors. somatostatin receptor 2 (SSTR2) is one of the human somatostatin receptors and highly implicated in cancers and neurological disorders. Here, we report the high resolution cryo-EM structure of full-length human SSTR2 bound to the agonist somatostatin (SST-14) complex with inhibitory G (Gi) proteins. Our structure shows that seven transmembrane helices form a deep pocket for ligand binding and that the highly conserved Trp-Lys motif of SST-14 positions at the bottom of the pocket. Furthermore, our sequence analysis combined with AlphaFold modeled structures of other SSTR isoforms provide how SSTR family proteins specifically interact with their cognate ligands. This work provides the first glimpse into the molecular recognition of somatostatin receptor and crucial resource to develop therapeutics targeting somatostatin receptors.