bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individualized Gaussian Process-based Prediction of Memory Performance and Biomarker Status in Ageing and Alzheimer’s disease
Authors: Nemali A. , Vockert N. , Berron D. , Maas A. , Yakupov R. , Peters O. , Gref D. , Cosma N. , Preis L. , Priller J. , Spruth E. , Altenstein S. , Lohse A. , Fliessbach K. , Kimmich O. , Vogt I. , Wiltfang J. , Hansen N. , Bartels C. , Schott B.H. , Maier F. , Meiberth D. , Glanz W. , Incesoy E. , Butryn M. , Buerger K. , Janowitz D. , Ewers M. , Perneczhy R. , Rauchmann B. , Burow L. , Teipel S. , Kilimann I. , Göerß D. , Dyrba M. , Laske C. , Munk M. , Sanzenbacher C. , Müller S. , Spottke A. , Roy N. , Heneka M. , Brosseron F. , Roeske S. , Dobisch L. , Ramirez A. , Ewers M. , Dechent P. , Scheffler K. , Kleineidam L. , Wolfsgruber S. , Wagner M. , Jessen F. , Duzel E. , Ziegler G. 
Published: March 2022

AbstractNeuroimaging markers based on Magnetic Resonance Imaging (MRI) combined with various other measures (such as informative covariates, vascular risks, brain activity, neuropsychological test etc.,) might provide useful predictions of clinical outcomes during progression towards Alzheimer’s disease (AD). The Bayesian approach aims to provide a trade-off by employing relevant features combinations to build decision support systems in clinical settings where uncertainties are relevant. We tested the approach in the MRI data across 959 subjects, aged 59-89 years and 453 subjects with available neuropsychological test scores and CSF biomarker status (amyloid-beta (Aβ)42/40 & and phosphorylated tau (pTau)) from a large sample multi-centric observational cohort (DELCODE). In order to explore the beneficial combinations of information from different sources, we presented a MRI-based predictive modelling of memory performance and CSF biomarker status (positive or negative) in the healthy ageing group as well as subjects at risk of Alzheimer’s disease using a Gaussian process multikernel framework. Furthermore, we systematically evaluated predictive combinations of input feature sets and their model variations, i.e. (A) combinations of brain tissue classes and feature type (modulated vs. unmodulated), choices of filter size of smoothing (ranging from 0 to 15 mm full width at half maximum), and image resolution (1mm, 2mm, 4mm and 8mm); (B) incorporating demography and covariates (C) the impact of the size of the training data set (i.e., number of subjects); (D) the influence of reducing the dimensions of data and (E) choice of kernel types. Finally, the approach was tested to reveal individual cognitive scores at follow-up (up to 4 years) using the baseline features. The highest accuracy for memory performance prediction was obtained for a combination of neuroimaging markers, demographics, genetic information (ApoE4) and CSF-biomarkers explaining 57% of outcome variance in out of sample predictions. The best accuracy for Aβ42/40 status classification was achieved for combination demographics, ApoE4 and memory score while usage of structural MRI improved the classification of individual patient’s pTau status.
Sharp wave ripples in macaque V1 and V4 are modulated by top-down visual attention
Authors: Doostmohammadi Jafar , Gieselmann Marc Alwin , van Kempen Jochem , Lashgari Reza , Yoonessi Ali , Thiele Alexander 
Published: March 2022

AbstractSharp-wave ripples (SWRs) are highly synchronous neuronal activity events. They have been predominantly observed in the hippocampus during offline states such as pause in exploration, slow-wave sleep and quiescent wakefulness. SWRs have been linked to memory consolidation, spatial navigation, and spatial decision-making. Recently, SWRs have been reported during visual search, a form of remote spatial exploration, in macaque hippocampus. However, the association between SWRs and multiple forms of awake conscious and goal-directed behavior is unknown. We report that ripple activity occurs in macaque visual areas V1 and V4 during focused spatial attention. The frequency of ripples is modulated by characteristics of the stimuli, by spatial attention directed toward a receptive field, and by the size of the attentional focus. Critically, the monkey’s reaction times in detecting behaviorally relevant stimulus changes was affected on trials with SWRs. These results show that ripple activity is not limited to hippocampal activity during offline states, rather they occur in the neocortex during active attentive states and vigilance behaviors.
A novel single layer microfluidic device for dynamic stimulation, culture and imaging of mammalian cells
Authors: Mustafa Adil , Pedone Elisa , La Regina Antonella , Erten Ahmet , Marucci Lucia 
Published: March 2022

AbstractThe possibility to tightly control the cellular microenvironment within microfluidic devices represents an important step forward precision analysis of cellular phenotypes in vitro. In particular, microfluidic platforms that allow both long-term mammalian cell culture and dynamic modulation of the culture environment can support quantitative studies of cells’ responses to drugs. Here, we report the design and testing of a novel microfluidic device of easy production (single Polydimethylsiloxane layer), which integrates a micromixer with vacuum-assisted cell loading for long-term mammalian cell culture and dynamic mixing of 4 different culture media. Finite element modelling was used to predict the flow rates and device dimensions to achieve diffusion-based fluid mixing. The device showed efficient mixing and dynamic exchange of media in the cell trapping chambers. This work represents the first attempt to integrate single layer microfluidic mixing devices with vacuum-assisted cell loading systems for mammalian cell culture and dynamic stimulation.
Neuroligin-3 in Dopaminergic Circuits Promotes Behavioral and Neurobiological Adaptations to Chronic Morphine Exposure
Authors: Brandner Dieter D. , Retzlaff Cassandra L. , Kocharian Adrina , Stieve Bethany J. , Mashal Mohammed A. , Mermelstein Paul G. , Rothwell Patrick E. 
Published: March 2022

ABSTRACTChronic opioid exposure causes structural and functional changes in brain circuits, which may contribute to opioid use disorders. Synaptic cell-adhesion molecules are prime candidates for mediating this opioid-evoked plasticity. Neuroligin-3 (NL3) is an X-linked postsynaptic adhesion protein that shapes synaptic function at multiple sites in the mesolimbic dopamine system. We therefore studied how genetic knockout of NL3 alters responses to chronic morphine in male mice. Constitutive NL3 knockout caused a persistent reduction in psychomotor sensitization after chronic morphine exposure and changed in the topography of locomotor stimulation produced by morphine. This latter change was recapitulated by conditional genetic deletion of NL3 from cells expressing the Drd1 dopamine receptor, whereas reduced psychomotor sensitization was recapitulated by conditional genetic deletion from dopamine neurons. Without NL3 expression, dopamine neurons in the ventral tegmental area exhibited diminished activation following chronic morphine exposure, by measuring in vivo calcium signals with fiber photometry. This altered pattern of dopamine neuron activity may be driven by aberrant forms of opioid-evoked synaptic plasticity in the absence of NL3: dopamine neurons lacking NL3 showed weaker synaptic inhibition at baseline, which was subsequently strengthened after chronic morphine. In total, our study highlights neurobiological adaptations in dopamine neurons of the ventral tegmental area that correspond with increased behavioral sensitivity to opioids, and further suggests that NL3 expression by dopamine neurons provides a molecular substrate for opioid-evoked adaptations in brain function and behavior.
Genetic affinities and adaptation of the South West coast populations of India
Authors: Kumar Lomous , Chowdhari Anuhya , Sequeira Jaison J. , Mustak Mohammed S. , Banerjee Moinak , Thangaraj Kumarasamy 
Published: March 2022

AbstractEvolutionary event has not only transformed the genetic structure of human populations but also associated with social and cultural transformation. South Asian populations were formed as a result of such evolutionary events of migration and admixture of genetically and culturally distinct groups. Most of the genetic studies pointed to large-scale admixture event between Ancestral North Indian (ANI) and Ancestral South Indian (ASI) groups, also additional layers of recent admixture. In the present study we have analyzed 213 individuals inhabited in South West coast India with traditional warriors and feudal lord status and historically associated with recent migrations events and possible admixture with Indo-Scythians, Saka, Huns and Kushans, whose genetic links are still missing. Analysis of autosomal SNP markers suggests that these groups possibly derived their ancestry from some groups of North West India having additional Middle Eastern genetic component and also their separation history suggests very early separation from North West Indian and Gangetic plain Indo-Europeans during late bronze or Iron age, most probably following central India and Godavari basin to South West coast. Higher distribution of west Eurasian mitochondrial haplogroups also points to admixture through maternal lineage. Selection screen using genome wide genealogy approach revealed genetic signatures related to their long-term coastal food habits. Thus, our study suggests that the South West coastal groups with traditional warriors and feudal lords’ status are of a distinct lineage compared to Dravidian and Gangetic plain Indo-Europeans and are remnants of very early migrations from North West India following Godavari basin to Karnataka and Kerala.
Neq2X7: a multi-purpose and open-source fusion DNA polymerase for advanced DNA engineering and diagnostics PCR
Authors: Hernández-Rollán Cristina , Ehrmann Anja K. , Nørholm Morten H. H. 
Published: March 2022

AbstractThermostable DNA polymerases, such as Taq isolated from the thermophilic bacterium Thermus aquaticus, enable one-pot exponential DNA amplification known as polymerase chain reaction (PCR). However, other properties than thermostability - such as fidelity, processivity, and compatibility with modified nucleotides - are important in contemporary molecular biology applications. Here, we describe the engineering and characterization of a fusion between a DNA polymerase identified in the marine archaea Nanoarchaeum equitans and a DNA binding domain from the thermophile Sulfolobus solfataricus. The fusion creates a highly active enzyme, Neq2X7, capable of amplifying long and GC-rich DNA and that is unaffected by replacing dTTP with dUTP in PCR. This makes it an attractive DNA polymerase for use e.g., with uracil excision (USER) DNA assembly and for contamination-free diagnostics. Furthermore, Neq2X7 is easy to produce, and the expression plasmid is freely available.Graphical abstract
Size-selective mortality fosters evolutionary changes in collective learning across ontogeny and decision-making in zebrafish,Danio rerio
Authors: Roy Tamal , Rohr Tabea , Arlinghaus Robert 
Published: March 2022

AbstractSize-selective harvesting evolutionary alters the life-history, behavioural and physiological traits in exploited fish populations. Changes in these traits may cause alteration in learning and decision-making abilities, either due to energetic trade-offs with brain investment that may vary across development or via correlations with boldness, sociability or other personality traits. Whether size-selective harvesting evolutionarily alters learning and decision-making abilities in fish remains unexplored, despite the global scale of fisheries. We tested the hypothesis that persistent removal of large-bodied individuals typical of many fisheries reduces learning ability in adults but not in juveniles, increases cognitive flexibility but reduces decision-making ability in adults. We examined associative learning through ontogeny, and reversal learning and collective decision-making in adults in three selection lines of zebrafish (Danio rerio)generated through positive, negative and random size-selective harvesting for five generations. Fish groups of each selection line were tested across ontogeny using a colour-discrimination paradigm with a food reward. The associative reversal task was conducted with a social reward, and the propensity to make group decisions was tested in an associative task. All selection lines showed significant learning ability and improved performance across ontogeny. Consistent with our hypothesis, the large-harvested line fish revealed a significantly reduced learning speed as subadults and adults, while the small-harvested line fish showed slower error rate compared to controls as 4-month old adults. We found no evidence of memory decay, and the selection lines did not vary in associative reversal ability. Decision-making speed did not vary across lines, but the large-harvested line made faster decisions during the probe trial. We conclude that size-selective harvesting typical of many fisheries evolutionarily alters learning and decision making. As this is likely to negatively and persistently affect resource acquisition and survival in exploited populations, we suggest that the cognition-related mechanism we identify may increase natural mortality.
Unleashing alternative polyadenylation analyses with REPAC
Authors: Imada Eddie L , Wilks Christopher , Langmead Ben , Marchionni Luigi 
Published: March 2022

AbstractAlternative polyadenylation (APA) is an important post-transcriptional mechanism that has major implications in biological processes and diseases. Although specialized sequencing methods for polyadenylation exist, their presence in public repositories is extremely limited when compared to traditional RNA-sequencing. To overcome this, we developed REPAC, a framework for the analysis of APA from RNA-sequencing data. REPAC implements a new method for detection of APA and is designed to take advantage ofrecount3which enables a streamlined way to analyze over 750,000 publicly available samples. Using REPAC, we investigated the landscape of APA caused by activation of B cells. Our analysis revealed that during this process, hundreds of genes are regulated by APA, most notably genes involved in the secretion pathway which is central for the transition to antibody-secreting B-cells. Moreover, we also showed that many genes associated with interferon response are also shortened, suggesting that APA might also play a significant role in the immune response. We also show that REPAC is faster than alternative methods by at least 7-fold and that it scales well to analysis involving hundreds of samples. Overall, the REPAC method offers an accurate, easy, and convenient solution for the exploration of APA across many phenotypes.
Does ankle push-off correct for errors in anterior-posterior foot placement relative to center-of-mass states?
Authors: Jin Jian , van Dieën Jaap H. , Kistemaker Dinant , Daffertshofer Andreas , Bruijn Sjoerd M. 
Published: March 2022

I.ABSTRACTUnderstanding the mechanisms humans use to stabilize walking is vital for predicting falls in elderly. Modeling studies identified two potential mechanisms to stabilize gait in the anterior-posterior direction: foot placement control and ankle push-off control: Foot placement depends on position and velocity of the center-of-mass (CoM) and push-off modulates with deviations between actual and predicted CoM trajectories. While both control mechanisms have been reported in humans, it is unknown whether especially the latter one is employed in unperturbed steady-state walking. On the one hand, the covariance between CoM states and anterior-posterior foot placement served as a measure of foot placement control. On the other hand, we determined variations in ankle push-off as a function of differences between the actual foot placement and the one predicted from CoM states. We estimated the corresponding correlations and consider them indictors for push-off control based on foot placement errors. We found ankle push-off torque to be correlated to the foot placement error in 30 participants when walking at normal and slow speed, with mean correlation values of up to 0.45. Our study suggests that humans use a push-off strategy for correcting foot placement errors in steady-state walking.
Nitrogen and phosphorus deficiencies alter primary and secondary metabolites of soybean roots
Authors: Nezamivand-Chegini Mahnaz , Metzger Sabine , Moghadam Ali , Tahmasebi Ahmad , Koprivova Anna , Eshghi Saeid , Mohammadi-Dehchesmeh Manijeh , Kopriva Stanislav , Niazi Ali , Ebrahimie Esmaeil 
Published: March 2022

AbstractNitrogen (N) and phosphorus (P) are two essential plant macronutrients that can limit plant growth by different mechanisms. We aimed to shed light on how soybean respond to low nitrogen (LN), low phosphorus (LP) and their combined deficiency (LNP). Generally, these conditions triggered changes in gene expression of the same processes, including cell wall organization, defense response, response to oxidative stress, and photosynthesis, however, response was different in each condition. A typical primary response to LN and LP was detected also in soybean, i.e., the enhanced uptake of N and P, respectively, by upregulation of genes for the corresponding transporters. The regulation of genes involved in cell wall organization showed that in LP roots tended to produce more casparian strip, in LN more secondary wall biosynthesis occurred, and in LNP reduction in expression of genes involved in secondary wall production accompanied by cell wall loosening was observed. Flavonoid biosynthesis also showed distinct pattern of regulation in different conditions: more anthocyanin production in LP, and more isoflavonoid production in LN and LNP, which we confirmed also on the metabolite level. Interestingly, in soybean the nutrient deficiencies reduced defense response by lowering expression of genes involved in defense response, suggesting a role of N and P nutrition in plant disease resistance. In conclusion, we provide detailed information on how LN, LP, and LNP affect different processes in soybean roots on the molecular and physiological levels.
Coevolution of Patch Selection in Stochastic Environments
Authors: Schreiber Sebastian J. , Hening Alexandru , Nguyen Dang H. 
Published: March 2022

AbstractSpecies interact in landscapes where environmental conditions vary in time and space. This variability impacts how species select habitat patches. Under equilibrium conditions, coevolution of this patch selection can result in ideal-free distributions where per-capita growth rates are zero in occupied patches and negative in unoccupied patches. These ideal-free distributions, however, don’t explain why species occupy sink patches, competitors have overlapping spatial ranges, or why predators avoid highly productive patches. To understand these patterns, we analyze multi-species Lotka-Volterra models accounting for spatial heterogeneity and environmental stochasticity. In occupied patches at the coESS, we show that the differences between the local contributions to the mean and the variance of the long-term population growth rate are equalized. Applying this characterization to models of antagonistic interactions reveals that environmental stochasticity can partially exorcize the ghost of competition past, select for new forms of enemy-free and victimless space, and generate Hydra effects over evolutionary time scales. Viewing our results through the economic lens of Modern Portfolio Theory highlights why the coESS for patch selection is often a bet-hedging strategy coupling stochastic sink populations. Our results highlight how environmental stochasticity can reverse or amplify evolutionary outcomes due to species interactions or spatial heterogeneity.
minute: A MINUTE-ChIP data analysis workflow
Authors: Navarro Carmen , Martin Marcel , Elsässer Simon 
Published: March 2022

AbstractQuantitative ChIP-seq methods are essential for accurately characterizing and comparing genome-wide DNA-protein interactions across samples. Procedures that enable such quantitative comparisons involve addition of spike-in chromatin or recombinant nucleosome material, or a multiplexed process using barcoding of chromatin fragments. ChIP-seq analysis workflows typically require a number of computational steps involving multiple tools in order to reach interpretable results, and quantitative analyses require additional steps that ensure scaling of the processed output according to the quantitative measurements. Crucially, the different quantitative approaches have unique analysis requirements reflecting the disparate experimental workflows, hence no universal analysis pipeline exists for quantitative ChIP-seq. Here, we developed minute, a user-friendly computational workflow to easily process multiplexed ChIP data that handles the specific needs of quantitative ChIP. minute enables transformation of raw, multiplexed FASTQ files into a set of normalized, scaled bigWig files that can serve as a basis for a quantitative, comparative downstream analysis. minute is implemented in Python and Snakemake and paired with a Conda environment, to facilitate usability and reproducibility in different platforms.Source code of minute is available on GitHub: https://github.com/NBISweden/minute
Mixture of Learning Strategies Underlies Rodent Behavior in Dynamic Foraging
Authors: Le Nhat Minh , Yildirim Murat , Wang Yizhi , Sugihara Hiroki , Jazayeri Mehrdad , Sur Mriganka 
Published: March 2022

ABSTRACTIn volatile foraging environments, animals need to adapt their learning in accordance with the uncertainty of the environment and knowledge of the hidden structure of the world. In these contexts, previous studies have distinguished between two types of strategies, model-free learning, where reward values are updated locally based on external feedback signals, and inference-based learning, where an internal model of the world is used to make optimal inferences about the current state of the environment. Distinguishing between these strategies during the dynamic foraging behavioral paradigm has been a challenging problem for studies of reward-guided decisions, due to the diversity in behavior of model-free and inference-based agents, as well as the complexities that arise when animals mix between these types of strategies. Here, we developed two solutions that jointly tackle these problems. First, we identified four key behavioral features that together benchmark the switching dynamics of agents in response to a change in reward contingency. We performed computational simulations to systematically measure these features for a large ensemble of model-free and inference-based agents, uncovering an organized structure of behavioral choices where observed behavior can be reliably classified into one of six distinct regimes in the two respective parameter spaces. Second, to address the challenge that arises when animals use multiple strategies within single sessions, we developed a novel state-space method, block Hidden Markov Model (blockHMM), to infer switches in discrete latent states that govern the choice sequences across blocks of trials. Our results revealed a remarkable degree of mixing between different strategies even in expert animals, such that model-free and inference-based learning modes often co-existed within single sessions. Together, these results invite a re-evaluation of the stationarity of behavior during dynamic foraging, provide a comprehensive set of tools to characterize the evolution of learning strategies, and form the basis of understanding neural circuits involved in different modes of behavior within this domain.