bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-task Learning and Ensemble Approach to Predict Cognitive Scores for Patients with Alzheimer’s Disease
Authors: Ma Daren , Pabalan Christabelle , Rajagopal Abhejit , Akanksha Akanksha , Interian Yannet , Yang Yang , Raj Ashish 
Published: December 2021

ABSTRACTDuring its chronic degenerative course, Alzheimer’s Disease severely harms the patients’ cognitive abilities. Assessment of current and future cognition is an integral component of a diagnosis of dementia, and therefore an important clinical and scientific goal. Unfortunately, subjective, time-consuming and operator-sensitive clinical surveys or neuropyschiatric batteries remain the only viable methods of assessing cognition. Given that MRI is the most prevalent, cost-effective, and clinically important imaging modality, it may be considered a suitable predictor of cognition. Yet, it has hitherto proved very challenging to predict one from the other. We propose that an image-based Deep Learning model can be custom-built to achieve this goal. We designed a novel multi-task UNet model to predict the subjects’ current and future cognition (via ADAS-Cog scores), taking as input baseline T1-weighted MRI and demographic risk factors. The key innovation in the model is that it seeks to solve two adjacent but relevant tasks: image segmentation into tissue types; and prediction of cognition. The first task gives a high-accuracy brain segmentation, comparable to other cutting edge methods. The features trained from the segmentation task are used in the cognition task. This combination is far superior to stand-alone single-shot cognition models. We achieved excellent accuracy in both baseline and time-series forecast of ADAS-Cog scores. Through further feature map analysis made on the receptive fields, we managed to impart much-needed model interpretability, critical for real-world clinical practice. This study constitutes the best-reported performance of any comparable approach, and opens the door towards machine-based tracking of AD progression.
Leaders are made: Learning acquisition of consistent leader-follower relationships depends on implicit haptic interactions
Authors: Takai Asuka , Fu Qiushi , Doibata Yuzuru , Lisi Giuseppe , Tsuchiya Toshiki , Mojtahedi Keivan , Yoshioka Toshinori , Kawato Mitsuo , Morimoto Jun , Santello Marco 
Published: December 2021

ABSTRACTAre leaders made or born? Leader-follower roles have been well characterized in social science, but they remain somewhat obscure in sensory-motor coordination. Furthermore, it is unknown how and why leader-follower relationships are acquired, including innate versus acquired controversies. We developed a novel asymmetrical coordination task in which two participants (dyad) need to collaborate in transporting a simulated beam while maintaining its horizontal attitude. This experimental paradigm was implemented by twin robotic manipulanda, simulated beam dynamics, haptic interactions, and a projection screen. Clear leader-follower relationships were learned despite participants not being informed that they were interacting with each other, but only when strong haptic feedback was introduced. For the first time, we demonstrate the emergence of consistent leader-follower relationships in sensory-motor coordination, and further show that haptic interaction is essential for dyadic co-adaptation. These results provide insights into neural mechanisms responsible for the formation of leader-follower relationships in our society.
HDfleX: Software for flexible high structural resolution of hydrogen/deuterium-exchange mass spectrometry data
Authors: Seetaloo Neeleema , Kish Monika , Phillips Jonathan J. 
Published: December 2021

ABSTRACTHydrogen/deuterium-exchange mass spectrometry (HDX-MS) experiments on protein structures can be performed at three levels: (1) by enzymatically digesting labelled proteins and analyzing the peptides (bottom-up), (2) by further fragmenting peptides following digestion (middle-down), and (3) by fragmenting the intact labelled protein (top-down), using soft gas-phase fragmentation methods, such as electron transfer dissociation (ETD). However, to the best of our knowledge, the software packages currently available for the analysis of HDX-MS data do not enable the peptide- and ETD-levels to be combined – they can only be analyzed separately. Thus, we developed HDfleX – a standalone application for the analysis of flexible high structural resolution of HDX-MS data, which allows data at any level of structural resolution (intact protein, peptide, fragment) to be merged. HDfleX features rapid experimental data fitting, robust statistical significance analyses and optional methods for theoretical intrinsic calculations and a novel empirical correction for comparison between solution conditions.
Life history adaptations to fluctuating environments: Combined effects of demographic buffering and lability of demographic parameters
Authors: Coeur Christie Le , Yoccoz Nigel G. , Salguero-Gómez Roberto , Vindenes Yngvild 
Published: December 2021

AbstractDemographic buffering and lability have been identified as adaptive strategies to optimise fitness in a fluctuating environment. These are not mutually exclusive, however we lack efficient methods to measure their relative importance for a given life history. Here, we decompose the stochastic growth rate (fitness) into components arising from nonlinear responses and variance-covariance of demographic parameters to an environmental driver, which allows studying joint effects of buffering and lability. We apply this decomposition for 154 animal matrix population models under different scenarios, to explore how these main fitness components vary across life histories. Faster-living species appear more responsive to environmental fluctuations, either positively or negatively. They have the highest potential for strong adaptive demographic lability, while demographic buffering is a main strategy in slow-living species. Our decomposition provides a comprehensive framework to study how organisms adapt to variability through buffering and lability, and to predict species responses to climate change.
Quantification of microbial robustness
Authors: Trivellin Cecilia , Olsson Lisbeth , Rugbjerg Peter 
Published: December 2021

AbstractStable cell performance in a fluctuating environment is essential for sustainable bioproduction and synthetic cell functionality; however, microbial robustness is rarely quantified. Here, we describe a high-throughput strategy for quantifying robustness of multiple cellular functions and strains in a perturbation space. We evaluated quantifications theory on experimental data and concluded that the mean-normalized Fano factor allowed accurate, reliable, and standardized quantification. Our methodology applied to perturbations related to lignocellulosic bioethanol production showed that Saccharomyces cerevisiae Ethanol Red exhibited both higher and more robust growth rates than CEN.PK and PE-2, while a more robust product yield traded off for lower mean levels. The methodology validated that robustness is function-specific and characterized by positive and negative function-specific trade-offs. Systematic quantification of robustness to end-use perturbations will be important to analyze and construct robust strains with more predictable functions.Graphical Abstract
Toxoplasma ERK7 defends the apical complex from premature degradation
Authors: O’Shaughnessy William J. , Hu Xiaoyu , Henriquez Sarah Ana , Reese Michael L. 
Published: December 2021

AbstractAccurate cellular replication balances the biogenesis and turnover of complex structures. In the apicomplexan parasiteToxoplasma gondii,daughter cells form within an intact mother cell, creating additional challenges to ensuring fidelity of division. The apical complex is critical to parasite infectivity and consists of apical secretory organelles and specialized cytoskeletal structures. We previously identified the kinase ERK7 as required for maturation of the apical complex inToxoplasma. Here we define theToxoplasmaERK7 interactome, including a putative E3 ligase, CSAR1. Genetic disruption of CSAR1 fully suppresses loss of the apical complex upon ERK7 knockdown. Furthermore, we show that CSAR1 is normally responsible for turnover of maternal cytoskeleton during cytokinesis, and that its aberrant function is driven by mislocalization from the parasite residual body to the apical complex. These data identify a protein homeostasis pathway critical forToxoplasmareplication and fitness and suggest an unappreciated role for the parasite residual body in compartmentalizing processes that threaten the fidelity of parasite development.
A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia
Authors: Voit Richard A. , Tao Liming , Yu Fulong , Cato Liam D. , Cohen Blake , Liao Xiaotian , Fiorini Claudia , Nandakumar Satish K. , Wahlster Lara , Teichert Kristian , Regev Aviv , Sankaran Vijay G. 
Published: December 2021

ABSTRACTThe molecular regulation of human hematopoietic stem cell (HSC) maintenance is therapeutically important, but limitations in experimental systems and interspecies variation have constrained our knowledge of this process. Here, we have studied a rare genetic disorder due toMECOMhaploinsufficiency, characterized by an early-onset absence of HSCsin vivo. By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC maintenance. Through our analyses, we nominate cooperating transcriptional regulators and identify how MECOM prevents the CTCF-dependent genome reorganization that occurs as HSCs differentiate. Strikingly, we show that this transcriptional network is co-opted in high-risk leukemias, thereby enabling these cancers to acquire stem cell properties. Collectively, we illuminate a regulatory network necessary for HSC self-renewal through the study of a rare experiment of nature.
Targeting targeted memory reactivation: characteristics of cued reactivation in sleep
Authors: Abdellahi Mahmoud E. A. , Koopman Anne C. M. , Treder Matthias S. , Lewis Penelope A. 
Published: December 2021

AbstractTargeted memory reactivation (TMR) is a technique in which sensory cues associated with memories during wake are used to trigger memory reactivation during subsequent sleep. The characteristics of such cued reactivation, and the optimal placement of TMR cues, remain to be determined. We built an EEG classification pipeline that discriminated reactivation of right- and left-handed movements and found that cues which fall on the up-going transition of the slow oscillation (SO) are more likely to elicit a classifiable reactivation. We also used a novel machine learning pipeline to predict the likelihood of eliciting a classifiable reactivation after each TMR cue using the presence of spindles and features of SOs. Finally, we found that reactivations occurred either immediately after the cue or one second later. These findings greatly extend our understanding of memory reactivation and pave the way for development of wearable technologies to efficiently enhance memory through cueing in sleep.
Inference for epidemic models with time varying infection rates: tracking the dynamics of oak processionary moth in the UK
Authors: Wadkin L E , Branson J , Hoppit A , Parker N G , Golightly A , Baggaley A W 
Published: December 2021

AbstractInvasive pests pose a great threat to forest, woodland and urban tree ecosystems. The oak processionary moth (OPM) is a destructive pest of oak trees, first reported in the UK in 2006. Despite great efforts to contain the outbreak within the original infested area of South-East England, OPM continues to spread.Here we analyse data of the numbers of OPM nests removed each year from two parks in London between 2013 and 2020. Using a state-of-the-art Bayesian inference scheme we estimate the parameters for a stochastic compartmental SIR (susceptible, infested, removed) model with a time varying infestation rate to describe the spread of OPM.We find that the infestation rate and subsequent basic reproduction number have remained constant since 2013 (withR0between one and two). This shows further controls must be taken to reduceR0below one and stop the advance of OPM into other areas of England.Synthesis.Our findings demonstrate the applicability of the SIR model to describing OPM spread and show that further controls are needed to reduce the infestation rate. The proposed statistical methodology is a powerful tool to explore the nature of a time varying infestation rate, applicable to other partially observed time series epidemic data.
Human cellular homeostasis buffers trans-acting translational effects of heterologous gene expression with very different codon usage bias
Authors: Jallet Arthur J , Demange Antonin , Leblay Fiona , Decourcelle Mathilde , El Koulali Khadija , Picard Marion AL , Bravo Ignacio G 
Published: December 2021

AbstractThe frequency of synonymous codons in protein coding genes is non-random and varies both between species and between genes within species. Whether this codon usage bias (CUBias) reflects underlying neutral mutational processes or is instead shaped by selection remains an open debate, especially regarding the role of selection for enhanced protein production. Variation in CUBias of a gene (be it natural synonymous mutations or biotechnological synonymous recoding) can have an enormous impact on its expression by diverse cis-acting mechanisms. But expression of genes with extreme CUBias can also lead to strong phenotypic effects by altering the overall intracellular translation homeostasis via competition for ribosomal machinery or tRNA depletion. In this study, we expressed at high levels in human cells six different synonymous versions of a gene and used matched transcriptomic and proteomic data to evaluate the impact of CUBias of the heterologous gene on the translation of cellular transcripts. Our experimental design focused specifically on differences during translation elongation. Response to expression of the different synonymous sequences was assessed by various approaches, ranging from analyses performed on a per-gene basis to more integrated approaches of the cell as a whole. We observe that the transcriptome displayed substantial changes as a result of heterologous gene expression by triggering an intense antiviral and inflammatory response, but that changes in the proteomes were very modest. Most importantly we notice that changes in translation efficiency of cellular transcripts were not associated with the direction of the CUBias of the heterologous sequences, thereby providing only limited support for trans-acting effects of synonymous changes. We interpret that, in human cells in culture, changes in CUBias can lead to important cis-acting effects in gene expression, but that cellular homeostasis can buffer the phenotypic impact of overexpression of heterologous genes with extreme CUBias.
A mosaic bulk-solvent model improves density maps and the fit between model and data
Authors: Afonine Pavel V. , Adams Paul D. , Sobolev Oleg V. , Urzhumtsev Alexandre 
Published: December 2021

AbstractBulk solvent is a major component of bio-macromolecular crystals and therefore contributes significantly to diffraction intensities. Accurate modeling of the bulk-solvent region has been recognized as important for many crystallographic calculations, from computing ofR-factors and density maps to model building and refinement. Owing to its simplicity and computational and modeling power, the flat (mask-based) bulk-solvent model introduced by Jiang & Brunger (1994) is used by most modern crystallographic software packages to account for disordered solvent. In this manuscript we describe further developments of the mask-based model that improves the fit between the model and the data and aids in map interpretation. The new algorithm, here referred to asmosaic bulk-solvent model, considers solvent variation across the unit cell. The mosaic model is implemented in the computational crystallography toolbox and can be used inPhenixin most contexts where accounting for bulk-solvent is required. It has been optimized and validated using a sufficiently large subset of the Protein Data Bank entries that have crystallographic data available.SynopsisA mosaic bulk-solvent method models disordered solvent more accurately than current flat bulk solvent model. This improves the fit between the model and the data, improves map quality and allows for the solution of problems previously inaccessible.
High-throughput submicron-resolution microscopy of entire C. elegans populations under strong immobilization by cooling cultivation plates
Authors: Wang Yao L. , Jaklitsch Erik L. , Grooms Noa W. F. , Schulting Leilani G. , Chung Samuel H. 
Published: December 2021

SummaryDespite its profound impact on biology, most high-resolution in vivo microscopy approaches remain low throughput because current immobilization techniques require significant manual effort. We greatly accelerate imaging of the nematode Caenorhabditis elegans by implementing a simple cooling approach to easily immobilize entire populations directly on their cultivation plates. We optimize and characterize cooling immobilization. Counterintuitively, relatively warmer temperatures immobilize animals significantly more effectively than colder temperatures utilized in prior studies. This enhanced immobilization enables clear submicron-resolution fluorescence imaging, which is challenging to achieve with most current immobilization techniques. We demonstrate 64× magnification 3D imaging and timelapse recording of neurons in adults and embryos without motion blur. Compared to standard azide immobilization, cooling immobilization reduces the animal preparation and recovery time by >98%, significantly increasing experimental speed. By obviating individual animal manipulation, our approach could also empower automated imaging of large C. elegans populations within standard experimental setups and workflows.
Contact sites between endoplasmic reticulum sheets and mitochondria regulate mitochondrial DNA replication and segregation
Authors: Ilamathi Hema Saranya , Benhammouda Sara , Lounas Amel , Al-Naemi Khalid , Desrochers-Goyette Justine , Lines Matthew A. , Richard François J. , Vogel Jackie , Germain Marc 
Published: December 2021

AbstractMitochondria are multi-faceted organelles crucial for cellular homeostasis that contain their own genome. Mitochondrial DNA (mtDNA) replication is a spatially regulated process essential for the maintenance of mitochondrial function, its defect causing mitochondrial diseases. mtDNA replication occurs at endoplasmic reticulum (ER)-mitochondria contact sites and is affected by mitochondrial dynamics: the absence of mitochondrial fusion is associated with mtDNA depletion whereas loss of mitochondrial fission causes the aggregation of mtDNA within abnormal structures termed mitobulbs. Here, we show that contact sites between mitochondria and ER sheets, the ER structure associated with protein synthesis, regulate mtDNA replication and distribution within mitochondrial networks. DRP1 loss or mutation leads to modified ER sheets and alters the interaction between ER sheets and mitochondria, disrupting RRBP1-SYNJ2BP interaction. Importantly, mtDNA distribution and replication were rescued by promoting ER sheets-mitochondria contact sites. Our work identifies the role of ER sheet-mitochondria contact sites in regulating mtDNA replication and distribution.
Biogenesis of a bacterial metabolosome for propanediol utilization
Authors: Yang Mengru , Wenner Nicolas , Dykes Gregory , Li Yan , Zhu Xiaojun , Sun Yaqi , Huang Fang , Hinton Jay C. D. , Liu Lu-Ning 
Published: December 2021

AbstractBacterial metabolosomes are a family of protein organelles in bacteria. Elucidating how thousands of proteins self-assemble to form functional metabolosomes is essential for understanding their significance in cellular metabolism and pathogenesis. Here we investigate thede novobiogenesis of propanediol-utilization (Pdu) metabolosomes and characterize the roles of the key constituents in generation and intracellular positioning of functional metabolosomes. Our results demonstrate that the Pdu metabolosome undertakes both “Shell first” and “Cargo first” assembly pathways, unlike the β-carboxysome structural analog which only involves the “Cargo first” strategy. Shell and cargo assemblies occur independently at the cell poles. The internal cargo core is formed through the ordered assembly of multiple enzyme complexes, and exhibits liquid-like properties within the metabolosome architecture. Our findings provide mechanistic insight into the molecular principles driving bacterial metabolosome assembly and expand our understanding of liquid-like organelle biogenesis.
Acute oral toxicity of zinc phosphide: an assessment for wild house mice in Australia
Authors: Hinds Lyn A. , Henry Steve , Van de Weyer Nikki , Robinson Freya , Ruscoe Wendy A. , Brown Peter R. 
Published: December 2021

AbstractBACKGROUNDThe efficacy of zinc phosphide (ZnP) for broadacre control of wild house mice in Australia is being reported by growers as increasingly variable. Have mice become less sensitive over time or are they taking a sub-lethal dose and developing aversion? In this laboratory study the sensitivity of groups of wild caught and an outbred laboratory strain of mice was assessed using oral gavage of a range of ZnP concentrations. The willingness of mice to consume ZnP-coated grains was then determined.RESULTSEach mouse group had very similar LD50 values (72 to 79 mg ZnP per kg body weight) which are significantly higher than previously reported. Time to death post-gavage ranged between 2.5 to 48 h. ZnP coated grains (50 g ZnP per kg grain) presented in the absence of alternative food were consumed and 94 percent of wild mice died. Mice provided with alternative food and ZnP coated wheat grains (either 25 or 50 g ZnP per kg grain) consumed toxic and non-toxic grains, and mortality was lower (33 to 55 percent). If a sublethal amount of ZnP coated grain was consumed, aversion occurred mostly in the presence of alternative food.CONCLUSIONSThe sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions ZnP coated grains coated with a new higher dose (50 g ZnP per kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. It is important to assess the efficacy of the higher ZnP dose per grain under natural field conditions, especially when background food is low.