bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXPLORE: A novel deep learning-based analysis method for exploration behaviour in object recognition tests
Authors: Ibañez Victor , Bohlen Laurens , Manuell Francesca , Mansuy Isabelle , Helmchen Fritjof , Wahl Anna-Sophia 
Published: June 2022

AbstractObject recognition tests are widely used in neuroscience to assess memory function in rodents. Despite the experimental simplicity of the task, the interpretation of behavioural features that are counted as object exploration can be complicated. Thus, object exploration is often analysed by manual scoring, which is time-consuming and variable across researchers. Current software using tracking points often lacks precision in capturing complex ethological behaviour. Switching or losing tracking points can bias outcome measures. To overcome these limitations we developed ”EXPLORE”, a simple, ready-to use and open source pipeline. EXPLORE consists of a convolutional neural network trained in a supervised manner, that extracts features from images and classifies behaviour of rodents near a presented object. EXPLORE achieves human-level accuracy in identifying and scoring exploration behaviour and outperforms commercial software with higher precision, higher versatility and lower time investment, in particular in complex situations. By labeling the respective training data set, users decide by themselves, which types of animal interactions on objects are in- or excluded, ensuring a precise analysis of exploration behaviour. A set of graphical user interfaces (GUIs) provides a beginning-to-end analysis of object recognition tests, accelerating a fast and reproducible data analysis without the need of expertise in programming or deep learning.
Heat denaturation enables multicolor X10-STED microscopy at single-digit nanometer resolution
Authors: Saal K.-A. , Shaib A.H. , Mougios N. , Crzan D. , Opazo F. , Rizzoli S.O. 
Published: June 2022

AbstractExpansion microscopy (ExM) improves imaging quality by physically enlarging the biological specimens. In principle, combining a large expansion factor with optical super-resolution should provide extremely high imaging precision. However, large expansion factors imply that the expanded specimens are dim and are therefore poorly suited for optical super-resolution. To solve this problem, we present a protocol that ensures the 10-fold expansion of the samples through high-temperature homogenization (X10ht). The resulting gels exhibited relatively high fluorescence intensity, enabling the sample analysis by multicolor stimulated emission depletion (STED) microscopy, for a final resolution of 6-8 nm. X10ht offers a more thorough homogenization than previous X10 protocols based on enzymatic digestion, and thereby enables the expansion of thick samples. The better epitope preservation also enables the use of nanobodies as labeling probes and the implementation of post-expansion signal amplification. We conclude that X10ht is a promising tool for nanoscale resolution in biological samples.
Liver Endothelium Microenvironment Promotes HER3-mediated Cell Growth in Pancreatic ductal adenocarcinoma
Authors: Zhang Wei , Wright Michel’le , Rathore Moeez , Zarei Mehrdad , Vaziri-Gohar Ali , Hajihassani Omid , Abbas Ata , Feng Hao , Brody Jonathan , Markowitz Sanford D , Winter Jordan , Wang Rui 
Published: June 2022

Abstract∼90% metastatic pancreatic ductal adenocarcinoma (mPDAC) occurs in the liver, and the 5-year survival rate for patients with mPDAC is only at 3%. We previously reported that liver endothelial cells (ECs) secreted soluble factors to promote colorectal cancer cell survival in a paracrine fashion. However, the effects of liver ECs on mPDAC have not been elucidated. In this study, we used primary ECs from non-neoplastic liver tissues. We treated PDAC cells with conditioned medium (CM) from liver ECs, with CM from PDAC as controls, and determined that liver EC-secreted factors increased PDAC cell growth. Using an unbiased receptor tyrosine kinase array, we identified human epidermal growth factor receptor 3 (HER3, also known as ErbB3) as a key mediator in EC-induced growth in PDAC cells that have HER3 expression (HER3 +ve). We found that EC-secreted neuregulins activated the HER3-AKT signaling axis, and that depleting neuregulins from EC CM or blocking HER3 with an antibody, seribantumab, attenuated EC-induced proliferation in HER3 +ve PDAC cells, but not in cells without HER3 expression. Furthermore, we determined that EC CM increased PDAC xenograft growth in vivo, and that seribantumab blocked EC-induced growth in xenografts with HER3 expression. These findings elucidated a paracrine role of liver ECs in promoting PDAC cell growth, and identified the HER3-AKT axis as a key mediator in EC-induced functions in PDAC cells with HER3 expression.Implicationsover 70% mPDAC express HER3. This study suggests the potential of using HER3-targeted therapies for treating patients with HER3 +ve mPDAC.
Supervised machine learning with feature selection for prioritization of targets related to time-based cellular dysfunction in aging
Authors: Truter Nina , van Rensburg Zuné Jansen , Oudrhiri Radouane , Singh Raminderpal , Louw Carla 
Published: June 2022

AbstractBackgroundGlobal life expectancy has been increasing without a corresponding increase in health span and with greater risk for aging-associated diseases such as Alzheimer’s disease (AD). An urgent need to delay the onset of aging-associated diseases has arisen and a dramatic increase in the number of potential molecular targets has led to the challenge of prioritizing targets to promote successful aging. Here, we developed a pipeline to prioritize aging-related genes which integrates the plethora of publicly available genomic, transcriptomic, proteomic and morphological data of C. elegans by applying a supervised machine learning approach. Additionally, a unique biological post-processing analysis of the computational output was performed to better reveal the prioritized gene’s function within the context of pathways and processes involved in aging across the lifespan of C. elegans.ResultsFour known aging-related genes — daf-2, involved in insulin signaling; let-363 and rsks-1, involved in mTOR signaling; age-1, involved in PI3 kinase signaling — were present in the top 10% of 4380 ranked genes related to different markers of cellular dysfunction, validating the computational output. Further, our ranked output showed that 91% of the top 438 ranked genes consisted of known genes on GenAge, while the remaining genes had thus far not yet been associated with aging-related processes.ConclusionThese ranked genes can be translated to known human orthologs potentially uncovering previously unknown information about the basic aging processes in humans. These genes (and their downstream pathways) could also serve as targets against aging-related diseases, such as AD.
Photografted zwitterionic hydrogel coating durability for reduced foreign body response to cochlear implants
Authors: Peel Adreann , Bennion Douglas M. , Horne Ryan , Hansen Marlan R. , Guymon C. Allan 
Published: June 2022

AbstractObjectiveDurability of photografted zwitterionic hydrogel coatings on cochlear implant biomaterials was examined to determine viability of these antifouling surfaces during insertion and long-term implant usage. Approach: Tribometry was used to determine the effect of zwitterionic coatings on lubricity of surfaces with varying hydration level, applied normal force, and timeframe. Additionally, flexural resistance was investigated using mandrel bending.Ex vivodurability was assessed by determining coefficient of friction between tissues and treated surfaces. Furthermore, cochlear implantation force was measured using cadaveric human cochleae. Main results: Hydrated zwitterionic hydrogel coatings reduced frictional resistance approximately 20-fold compared to uncoated PDMS, which importantly led to significantly lower mean force experienced by coated cochlear implants during insertion compared to uncoated systems. Under flexural force, zwitterionic films resisted failure for up to 60 minutes of desiccation. The large increase in lubricity was maintained for 20 hours under continual force while hydrated. For loosely crosslinked systems, films remained stable and lubricious even after rehydration following complete drying. All films remained hydrated and functional under frictional force for at least 30 minutes in ambient conditions while drying, with lower crosslink densities showing the greatest longevity. Moreover, photografted zwitterionic hydrogel samples showed no evidence of degradation and nearly identical lubricity before and after implantation. Significance: This work demonstrates that photografted zwitterionic hydrogel coatings are sufficiently durable to maintain viability before, during, and after implantation. Mechanical properties, including greatly increased lubricity, are preserved after complete drying and rehydration for various applied forces. Additionally, this significantly enhanced lubricity translates to significantly decreased force during insertion of implants which should result in less trauma and scarring.
Expression Microdissection for use in qPCR based analysis of miRNA in a single cell type
Authors: Jenike Ana E. , Bunkelman Brady , Perzel Mandell Kira A. , Oduor Cliff , Chin Deborah , Mair Devin , Jenike Katharine M. , Kim Deok-Ho , Bailey Jeffrey A. , Rafailovich Miriam H. , Rosenberg Avi Z. , Halushka Marc K. 
Published: June 2022

ABSTRACTCell-specific microRNA (miRNA) expression estimates are important in characterizing the localization of miRNA signaling within tissues. Much of this data is obtained from cultured cells, a process known to significantly alter miRNA expression levels. Thus, our knowledge of in vivo cell miRNA expression estimates is poor. We previously demonstrated expression microdissection-miRNA-sequencing (xMD-miRNA-seq) as a means to acquire in vivo estimates, directly from formalin fixed tissues, albeit with limited yield. Here we optimized each step of the xMD process including tissue retrieval, tissue transfer, film preparation, and RNA isolation to increase RNA yields and ultimately show strong enrichment for in vivo miRNA expression by qPCR array. These method improvements, including the development of a non-crosslinked ethylene vinyl acetate (EVA) membrane, resulted in a 23-45 fold increase in miRNA yield, depending on cell type. By qPCR, miR-200a was increased 14-fold in xMD-derived small intestine epithelial cells, with a concurrent 336-fold reduction in miR-143, relative to the matched non-dissected duodenal tissue. xMD is now an optimized method to obtain robust in vivo miRNA expression estimates from cells.
Mapping the semi-nested community structure of 3D chromosome contact networks
Authors: Bernenko Dolores , Lee Sang Hoon , Stenberg Per , Lizana Ludvig 
Published: June 2022

ABSTRACTMammalian DNA folds into 3D structures that facilitate and regulate genetic processes such as transcription, DNA repair, and epigenetics. Several insights derive from chromosome capture methods, such as Hi-C, which allow researchers to construct contact maps depicting 3D interactions among all DNA segment pairs. These maps show a complex cross-scale organization spanning megabase-pair compartments to short-ranged DNA loops. To better understand the organizing principles, several groups analyzed Hi-C data assuming a Russian-doll-like nested hierarchy where DNA regions of similar sizes merge into larger and larger structures. Apart from being a simple and appealing description, this model explains, e.g., the omnipresent chequerboard pattern seen in Hi-C maps, known as A/B compartments, and foreshadows the co-localization of some functionally similar DNA regions. However, while successful, this model is incompatible with the two competing mechanisms that seem to shape a significant part of the chromosomes’ 3D organization: loop extrusion and phase separation. This paper aims to map out the chromosome’s actual folding hierarchy from empirical data. To this end, we take advantage of Hi-C experiments and treat the measured DNA-DNA interactions as a weighted network. From such a network, we extract 3D communities using the generalized Louvain algorithm. This algorithm has a resolution parameter that allows us to scan seamlessly through the community size spectrum, from A/B compartments to topologically associated domains (TADs). By constructing a hierarchical tree connecting these communities, we find that chromosomes are more complex than a perfect hierarchy. Analyzing how communities nest relative to a simple folding model, we found that chromosomes exhibit a significant portion of nested and non-nested community pairs alongside considerable randomness. In addition, by examining nesting and chromatin types, we discovered that nested parts are often associated with active chromatin. These results highlight that crossscale relationships will be essential components in models aiming to reach a deep understanding of the causal mechanisms of chromosome folding.
PhysiCell training apps: A case study for creating interactive training materials for scientific software packages
Authors: Sundus Aneequa , Kurtoglu Furkan , Konstantinopoulos Kali , Chen Mary , Willis Drew , Heiland Randy , Macklin Paul 
Published: June 2022

AbstractCell-based tissue simulations require not only the ability to write new code in a simulation framework, but also an understanding of underlying mathematical models, background biology, and parameters for each behavior of an agent. This can entail a steep learning curve for interdisciplinary researchers joining computational biology research. We have created a suite of cloud-hosted open-source tools to separately explore and learn key components of an agent-based cellular simulation framework. This creates an self-contained environment to learn and test functions of cells and the micro-environment in a modular fashion before creating more detailed, research-focused simulation models.
Are cell wall traits a component of the succulent syndrome?
Authors: Fradera-Soler Marc , Leverett Alistair , Mravec Jozef , Jørgensen Bodil , Borland Anne M. , Grace Olwen M. 
Published: June 2022

AbstractSucculence is an adaptation to low water availability characterised by the presence of water-storage tissues that alleviate water stress under low water availability. The succulent syndrome has evolved convergently in over 80 plant families and is associated with anatomical, physiological and biochemical traits. Despite the alleged importance of cell wall traits in drought responses, their significance in the succulent syndrome has long been overlooked. Here, by analysing published pressure–volume curves, we show that elastic adjustment, whereby plants change cell wall elasticity, is uniquely beneficial to succulents for avoiding turgor loss. In addition, we used comprehensive microarray polymer profiling (CoMPP) to assess the biochemical composition of cell walls in leaves. Across phylogenetically diverse species, we uncover several differences in cell wall biochemistry between succulent and non-succulent leaves, pointing to the existence of a ‘succulent glycome’. We also highlight the glycomic diversity among succulent plants, with some glycomic features being restricted to certain succulent lineages. In conclusion, we suggest that cell wall biomechanics and biochemistry should be considered among the characteristic traits that make up the succulent syndrome.
Renal ischemia-reperfusion injury attenuated by exosomes extracted from splenic ischemic preconditioning
Authors: Hongtao Liu , Ye Shen 
Published: June 2022

AbstractObjectiveTo investigate the protective effects of the exosomes extracted from splenic ischemic preconditioning (sIPC) on renal ischemia-reperfusion (IR) injury.Materials and methodsSplenic ischemic preconditioning(sIPC)was conducted on mice in vivo 24 hours before the start of renal ischemia-reperfusion (IR) injury experiment, and serum exosomes derived from sIPC mice were infused into the mice model of renal ischemia-reperfusion injury. The kidney tissue and serum were collected 24 hours later. The morphological changes and inflammation in ischemia-reperfusion kidneys were determined by hematoxylin-eosin (HE) staining.Then the apoptosis of kidney tissue sections were detected by TUNEL staining, Ki-67 immunohistochemical staining was used to assess the proliferation.In addition, the levels of pro-inflammatory cytokines including TNF-α, IL-1β and SCr in serum were measured by ELISA.In vitro, we extracted exosomes from mouse spleen fibroblasts pretreated with hypoxia and reoxygenation (H/R) and administered them to mouse renal epithelial cells.Furthermore, for the hypoxia-reoxygenation model of renal epithelial cells, TUNEL and flow cytometry were used to evalutaed cell apoptosis;Then ELISA was used to measure the levels of TNF-α and IL-1β in the cell supernatant, Bax and Bcl-2 were measured by Western Blotting.ResultsHE staining showed that the renal injury caused by ischemia-reperfusion attenuated after sIPC. TUNEL staining showed that renal tissue apoptosis was greatly reduced after sIPC or injection of exosomes extracted from splenic fibroblast hypoxia-reoxygenation model. Ki-67 staining showed that the positive rates of IRI+sIPC group, IRI+mSF(H/R)-exo group, IRI+mSF(H/R+PBS)-exo group were close, higher than IRI group but lower than sham group. ELISA test of kidney tissue showed that the serum creatinine, TNF-α and IL-1β induced by IRI decreased with sIPC and addition of the above-mentioned exosomes.In vitro, the exosomes extracted from the hypoxia-reoxygenation model of splenic fibroblasts had the same protective effect on hypoxia-reoxygenated mouse renal epithelial cells model, and this protective effect disappears after the addition of exosome inhibitors.TUNEL and flow cytometry showed that the exosomes reduced the apoptosis. The ELISA test results showed that the levels of TNF-α and IL-1β in the H/R group increased significantly, but decreased due to the splenic fibroblast exosomes treated with starvation.While the exosome inhibitors inhibited the effects of exosomes.Western blot results showed that the Bax expression level of the H/R group increased, and the Bcl-2 decreased.While the starvation-treated splenic fibroblast exosomes decreased the Bax level and increased the Bcl-2 level.ConclusionsThe exosomes extracted from splenic ischemic preconditioning exerted a protective capacity to attenuate renal IR injury.
A topological method of generating action potentials and EEG oscillations in a surface network
Authors: Sen Siddhartha 
Published: June 2022

AbstractA wide variety of electrical activities are observed to occur in the brain. They include one dimensional voltage pulses (action potentials) that propagate along nerve fibers, transient localized oscillations, and persistent surface waveforms oscillating in five distinct frequency bands, called EEG waveforms. However, although a satisfactory theory for propagating pulses exists a unified theoretical framework for modeling all its excitations is lacking. In this paper we construct a special surface network in which all observed brain-like signals can be generated by topological means. The network has surface electrons,is, as we will prove, an exact topological surface representation of the unknown intricate connectivity architecture of the brain’s nerve fibers, and its surface has a mathematical representation. A dynamical law which requires that all input and out put signals of the network respect the mathematical structure of the surface is used to study the network. Using this law it is shown that all brain-like signals can be generated by input signals that locally deform the surface of a subunit of the network, transiently, reducing its topology to that of a sphere. The topological spheres thus produced have surface voltage oscillating waveforms in five theoretically determined frequencies bands and are identified as EEG waveforms. Methods for analyzing these waveforms are developed and used to explain their observed deep sleep structures and determine their properties.
Accurate background reduction in adaptive optical 3D-STED nanoscopy by dynamic phase switching
Authors: Tu Shijie , Liu Xin , Yuan Difu , Tao Wenli , Han Yubing , Shi Yan , Li Yanghui , Kuang Cuifang , Liu Xu , Yao Yufeng , Xu Yesheng , Hao Xiang 
Published: June 2022

ABSTRACTStimulated emission depletion (STED) fluorescence nanoscopy allows the three-dimensional (3D) visualization of nanoscale subcellular structures, providing unique insights into their spatial organization. However, 3D-STED imaging and quantification of dense features are obstructed by the low signal-to-background ratio (SBR), resulting from optical aberrations and out-of-focus background. Here, combining with adaptive optics, we present an easy-to-implement and flexible method to improve SBR by dynamic phase switching. By switching to a counterclockwise vortex phase mask and a top-hat one with an incorrect inner radius, the depletion pattern features a nonzero-intensity center, enabling accurate background recordings. When the recorded background is subtracted from the aberration-corrected 3D-STED image, the SBR in dense sample areas can be improved by a factor of 3–6 times. We demonstrate our method on various dense subcellular structures, showing more advantages than the software-based background subtraction algorithms.Abstract Figure
Intense sexual conflict affects the female choice strategy in the gregarious desert locust
Authors: Golov Y. , Lavy O. , Halon E. , Rillich J. , Ayali A. , Harari A 
Published: June 2022

Disclaimer statementThe authors have withdrawn their manuscript due to disagreement of several aspects regarding the interpretation of the results reported in this paper. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Chronic infection control relies on T cells with lower foreign antigen binding strength generated by N-nucleotide diversity
Authors: Jamaleddine Hassan , Rogers Dakota , Perreault Geneviève , Mandl Judith N. , Khadra Anmar 
Published: June 2022

SummaryThe pathogens to which T cells respond is determined by the T cell receptors (TCRs) present in an individual’s repertoire. Although more than 90% of the TCR repertoire is generated by terminal deoxynucleotidyl transferase (TdT)-mediated N-nucleotide addition during V(D)J recombination, the benefit of TdT-modified TCRs remains unclear. Here, we computationally and experimentally investigated whether TdT systematically modifies the affinity distribution of a TCR repertoire in ways that impacts acute or chronic infection. Our computational model predicts a shift toward low-affinity T cells over time during chronic, but not acute, infections. Elimination of low-affinity T cellsin silicosubstantially delayed chronic infection clearance. Corroborating an affinity-centric benefit for TCR diversity, we showed that infection of TdT-deficient mice delayed the clearance of a chronic viral pathogen, while acute viral control was unaffected. Our data thus suggest that TdT-mediated TCR diversity is of particular benefit in the control of prolonged pathogen replication.