bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitat resource overlap in two broad-ranged sympatric Neotropical forest eagles
Authors: Sutton Luke J. , Anderson David L. , Franco Miguel , Gomes Felipe Bittioli R. , McClure Christopher J.W. , Miranda Everton B.P. , Vargas F. Hernán , Vargas González José de J. , Puschendorf Robert 
Published: March 2022

AbstractQuantifying resource partitioning between co-occurring species has important ecological and evolutionary implications. Yet, few studies compare resource overlap in both geographic and environmental space. We test whether the habitat requirements of two closely related Neotropical forest eagles, the crested eagle (Morphnus guianensis) and harpy eagle (Harpia harpyja), differ at fine and coarse resolutions across their shared geographic range. Using landcover and topographic covariates, we quantified resource overlap first using higher resolution (30 arc-sec data) generalized linear models (GLMs), and second using coarser-grain (2.5 arc-min data) environmental ordination. The distribution of both eagles was largely explained by canopy species richness and structural complexity with evergreen forest, but with differing responses to landcover and topography, particularly with the harpy eagle more likely in areas of dense evergreen forest. Both eagles were negatively associated with mosaic forest, with this relationship stronger for the crested eagle. Harpy eagle distribution was restricted by higher elevation and terrain roughness, compared to the crested eagle, whose distribution was more restricted by canopy species richness and structure. From the GLMs, resource overlap was > 92 % in geographical space but reduced to 64 % in environmental space. From ordination, resource overlap was 76 % in environmental space, with randomization tests supporting equivalent environmental space for both eagles. Our results suggest that at the biogeographical scale, crested and harpy eagles share environmental space, but there may be subtle differences in fine-scale habitat preference. We recommend habitat resource overlap be assessed in both geographical and environmental space at multiple resolutions to capture the inherent variability in environmental conditions available to co-occurring species.
Structural and functional MRI data differentially predict chronological age and behavioral memory performance
Authors: Soch Joram , Richter Anni , Kizilirmak Jasmin M. , Schütze Hartmut , Feldhoff Hannah , Fischer Larissa , Knopf Lea , Raschick Matthias , Schult Annika , Düzel Emrah , Schott Björn H. 
Published: March 2022

AbstractHuman cognitive abilities decline with increasing chronological age, with decreased explicit memory performance being most strongly affected. However, some older adults show “successful aging”, that is, relatively preserved cognitive ability in old age. One explanation for this could be higher brain structural integrity in these individuals. Alternatively, the brain might recruit existing resources more efficiently or employ compensatory cognitive strategies. Here, we approached this question by testing multiple candidate variables from structural and functional neuroimaging for their ability to predict chronological age and memory performance, respectively. Prediction was performed using support vector machine (SVM) classification and regression across and within two samples of young (N = 106) and older (N = 153) adults. The candidate variables were (i) behavioral response frequencies in an episodic memory test, (ii) recently described fMRI scores reflecting preservation of functional memory networks, (iii) whole-brain fMRI contrasts for novelty processing and subsequent memory, (iv) resting-state fMRI maps quantifying voxel-wise signal fluctuation and (v) gray matter volume estimated from structural MR images. While age group could be reliably decoded from all variables, chronological age within young and older subjects was best predicted from gray matter volume. In contrast, memory performance was best predicted from task-based fMRI contrasts and particularly single-value fMRI scores, whereas gray matter volume has no predictive power with respect to memory performance in healthy adults. Our results suggest that superior memory performance in healthy older adults is better explained by efficient recruitment of memory networks rather than by preserved brain structure.
Improving patient survival by direct targeting of chimeric protein-protein interaction networks
Authors: Tagore Somnath , Frenkel-Morgenstern Milana 
Published: March 2022

AbstractProtein fusions produced by the “slippage” of two genes or by chromosomal translocations are essential diagnostic biomarkers of cancer. Fusions produce novel protein-protein interactions, which eliminate other interactions by changing protein domains in such fusions. The impact of these changes disseminates along protein-protein interaction networks, thereby altering cancer-promoting activity and creating cancer phenotypes. Currently, for most patients, the determination of appropriate drugs is totally empirical. As such, a personalized therapy approach based on unique patient genomic markers is needed. In this study, we considered 672 aliquot IDs containing 3091 fusions from The Cancer Genome Atlas (TCGA), accounting for 25 cancer sub-types assigned as leukemias, lymphomas, sarcomas, melanoma, glioblastoma and carcinomas. Protein-protein interaction maps showed distinct patterns according to cancer sub-type, reflected as different phenotypic traits. We induced site-directed percolations, i.e., critical transitions, by selective knockouts of genes encoding proteins in a given interaction network so as to identify breakdown points. The number of genes that needed to be knocked out in a site-directed manner before inducing a breakdown ranged from 1-7 based on whether the fusion protein was part of a network hub. Quantitatively, in leukemia, lymphoma, melanoma and glioblastoma, breakdown was achieved in 218 fusion networks when only higher degree hubs were percolated, and in 280 networks when a combination of higher and lower degree hubs was targeted, with an FDR < 0.05. These were subsequently addressed in survival studies. We found that patient survival may be improved by considering ‘breakdown points’ as drug targets.
Temporal dynamics of cognitive flexibility in adolescents with anorexia nervosa: a high density EEG study
Authors: Berchio Cristina , Annen Lucie Clémentine , Bouamoud Ynès , Micali Nadia 
Published: March 2022

AbstractCognitive rigidity is a core symptom of anorexia nervosa (AN) and is associated with treatment resistance. Nevertheless, studies on the neural basis of cognitive flexibility (CF) in adolescent AN are rare.The aim of this study was to investigate temporal brain dynamics of CF in adolescents with AN and their tendency to experience anxiety. To address this aim, participants performed a Dimensional Change Card Sorting task during high-density EEG recording. Transient state and stable traits of anxiety were measured with the State-Trait Anxiety Inventory. Data were collected on 22 girls with AN, and 23 healthy controls (HC) (aged 12-20 years old). Evoked potentials were investigated using microstates analysis. Effects of trait and state anxiety on microstates parameters were investigated performing correlations across groups and in the AN group only.Adolescents with AN did not differ from HC with respect to behavioral switching cost, despite a greater overall accuracy. Adolescents with AN showed altered visual orienting processes (N100 micro-state), and earlier attentional processing to task switching (P300b microstate) when compared to HC. Reduced activation in a network involving the pre-central cortex, the cerebellum, and the posterior cingulate was identified in adolescents with AN. Trait and state anxiety were correlated with atypical AN microstates across groups.The present findings suggest CF manifests with inefficient behavioral and neural strategies in adolescents with AN, at early stages in the illness. Additionally, this study provides evidence that transient and stable tendencies to experience anxiety could represent a vulnerability to developing CF impairments in adolescent AN.
Stable working memory and perceptual representations in macaque lateral prefrontal cortex during naturalistic vision
Authors: Roussy Megan , Corrigan Benjamin , Luna Rogelio , Gulli Roberto A. , Sachs Adam J. , Palaniyappan Lena , Martinez-Trujillo Julio C. 
Published: March 2022

Primates use perceptual and mnemonic visuospatial representations to perform everyday functions. Neurons in the lateral prefrontal cortex (LPFC) have been shown to encode both of these representations during tasks where eye movements are strictly controlled and visual stimuli are reduced in complexity. This raises the question of whether perceptual and mnemonic representations encoded by LPFC neurons remain robust during naturalistic vision — in the presence of a rich visual scenery and during eye movements. Here we investigate this issue by training macaque monkeys to perform working memory and perception tasks in a visually complex virtual environment that requires navigation using a joystick and allows for free visual exploration of the scene. We recorded the activity of 3950 neurons in the LPFC (areas 8a and 9/46) of two rhesus macaques using multi-electrode arrays, and measured eye movements using video tracking. We found that navigation trajectories to target locations and eye movement behavior differed between the perception and working memory tasks suggesting that animals employed different behavioral strategies. Single neurons were tuned to target location during cue encoding and working memory delay and neural ensemble activity was predictive of the animals’ behavior. Neural decoding of target location was stable throughout the working memory delay epoch. However, neural representations of similar target locations differed between the working memory and perception tasks. These findings indicate that during naturalistic vision, LPFC neurons maintain robust and distinct neural codes for mnemonic and perceptual visuospatial representations.Significance StatementWe show that LPFC neurons encode working memory and perceptual representations during a naturalistic task set in a virtual environment. We show that despite eye movement and complex visual input, neurons maintain robust working memory representations of space which are distinct from neuronal representations for perception. We further provide novel insight on the use of virtual environments to construct behavioral tasks for electrophysiological experiments.
siRNA-mediated gene knockdown via electroporation in hydrozoan jellyfish embryos
Authors: Masuda-Ozawa Tokiha , Fujita Sosuke , Nakamura Ryotaro , Watanabe Hiroshi , Kuranaga Erina , Nakajima Yu-ichiro 
Published: March 2022

AbstractAs the sister group to bilaterians, cnidarians stand in a unique phylogenetic position that provides insight into evolutionary aspects of animal development, physiology, and behavior. While cnidarians are classified into two types, sessile polyps and free-swimming medusae, most studies at the cellular and molecular levels have been conducted on representative polyp-type cnidarians and have focused on establishing techniques of genetic manipulation. Recently, gene knockdown by delivery of short hairpin RNAs into eggs via electroporation has been introduced in two polyp-type cnidarians, Nematostella vectensis and Hydractinia symbiolongicarpus, enabling systematic loss-of-function experiments. By contrast, current methods of genetic manipulation for most medusa-type cnidarians, or jellyfish, are quite limited, except for Clytia hemisphaerica, and reliable techniques are required to interrogate function of specific genes in different jellyfish species. Here, we present a method to knock down target genes by delivering small interfering RNA (siRNA) into fertilized eggs via electroporation, using the hydrozoan jellyfish, Clytia hemisphaerica and Cladonema paciificum. We show that siRNAs targeting endogenous GFP1 and Wnt3 in Clytia efficiently knock down gene expression and result in known planula phenotypes: loss of green fluorescence and defects in axial patterning, respectively. We also successfully knock down endogenous Wnt3 in Cladonema by siRNA electroporation, which circumvents the technical difficulty of microinjecting small eggs. Wnt3 knockdown in Cladonema causes gene expression changes in axial markers, suggesting a conserved Wnt/β-catenin-mediated pathway that controls axial polarity during embryogenesis. Our gene-targeting siRNA electroporation method is applicable to other animals, including and beyond jellyfish species, and will facilitate the investigation and understanding of myriad aspects of animal development.
Resting-state connectivity underlying cognitive control’s association with perspective taking in callous-unemotional traits
Authors: Winters Drew E. , Leopold Daniel R. , McKell Carter R. , Sakai Joseph T. 
Published: March 2022

AbstractCallous-Unemotional (CU) traits are often associated with impairments in perspective taking and cognitive control (regulating goal directed behavior); and adolescents with CU traits demonstrate aberrant brain activation/connectivity in areas underlying these processes. Together cognitive control and perspective taking are thought to link mechanistically to explain CU traits. Because increased cognitive control demands modulate perspective taking ability among both typically developing samples and individuals with elevated CU traits, understanding the neurophysiological substrates of these constructs could inform efforts to alleviate societal costs of antisocial behavior. The present study uses GIMME to examine the heterogenous functional brain properties (i.e., connection density, node centrality) underlying cognitive control’s influence on perspective taking among adolescents on a CU trait continuum. Results reveal that cognitive control had a negative indirect association with CU traits via perspective taking; and brain connectivity indirectly associated with lower CU traits – specifically the social network via perspective taking and conflict network via cognitive control. Additionally, less negative connection density between the social and conflict networks was directly associated with higher CU traits. Our results support the growing literature on cognitive control’s influence on socio-cognitive functioning in CU traits and extends that work by identifying underlying functional brain properties.
Exploring intra-species diversity through non-redundant pangenome assemblies
Authors: Puente-Sánchez Fernando , Hoetzinger Matthias , Buck Moritz , Bertilsson Stefan 
Published: March 2022

ABSTRACTAt the genome level, microorganisms are highly adaptable both in terms of allele and gene composition. Such heritable traits emerge in response to different environmental niches and can have a profound influence on microbial community dynamics. As a consequence of this, any individual genome or clonal population will contain merely a fraction of the total genetic diversity of any operationally defined “species”, with the collective from that group presenting the broader genomic diversity known as the pangenome. Pangenomes are valuable concepts for studying evolution and adaptation in microorganisms, as they partition genomes into core regions (present in all the genomes, and responsible for housekeeping and species-level niche adaptation) and accessory regions (present only in some genomes, and responsible for ecotype divergence).Here we present SuperPang, an algorithm capable of producing pangenome assemblies from a set of input genomes of varying quality, including metagenome-assembled genomes or MAGs. SuperPang runs in linear time and its results are complete, non-redundant, preserve gene ordering and contain both coding and non-coding regions. Our approach provides a modular view of the pangenome, identifying operons and genomic islands, and allowing to track their prevalence in different populations. We illustrate our approach by analyzing the intra-species diversity of Polynucleobacter, a clade of ubiquitous freshwater microorganisms characterized by their streamlined genomes and their ecological versatility. We show how SuperPang facilitates the simultaneous analysis of allelic and gene content variation under different environmental pressures, allowing us to study the drivers of microbial diversification at unprecedented resolution.
Xenon LFP Analysis Platform is a Novel Graphical User Interface for Analysis of Local Field Potential from Large-Scale MEA Recordings
Authors: Mahadevan Arjun , Codadu Neela K. , Parrish R. Ryley 
Published: March 2022

AbstractHigh-density multi-electrode array (HD-MEA) has enabled neuronal measurements at high spatial resolution to record local field potentials (LFP), extracellular spikes, and network activity with ease. Whilst we have advanced recording systems with over 4000 electrodes, capable of recording data at over 20 kHz, it still presents computational challenges to handle, process, extract, and view information from these large recordings. It can be challenging for researchers to extract and view even a single channel that has more than a billion data points, let alone process a group of channels.We have created a computational method, and an open-source toolkit built on Python, rendered on a web browser using Plotly’s Dash for extracting and viewing the data, and creating interactive visualization. In addition to extracting and viewing entire or small chunks of data sampled at lower or higher frequencies, respectively, it provides a framework to collect user inputs, analyze channel groups, generate raster plots, view quick summary measures for LFP activity, detect and isolate noise channels, and generate plots and visualization in both time and frequency domain. Incorporated into our Graphical User Interface (GUI), we also have created a novel seizure detection method, which can be used to detect the onset of seizures in all or a selected group of channels and provide the following measures of seizures: distance, duration, and propagation across the region of interest.We demonstrate the utility of this toolkit, using datasets collected from the 3Brain BioCAM duplex system. For the current analysis, we demonstrate the toolkit and methods with a low sampling frequency dataset (300 Hz) and a group of approximately 400 channels. Using this toolkit, we present novel data demonstrating increased seizure propagation speed from slices of Scn1aHet mice compared to littermate controls.With advances in HD-MEA recording systems with high spatial and temporal resolution, limited tools are available for researchers to view and process these big datasets. We now provide a user-friendly toolkit to analyze LFP activity obtained from large-scale MEA recordings with translatable applications to EEG recordings, and demonstrate the utility of this new graphic user interface with novel biological findings.
AMP-kinase mediates adaptation of glioblastoma cells to conditions of the tumour microenvironment
Authors: Lorenz Nadja I. , Sauer Benedikt , Zeiner Pia S. , Strecker Maja I. , Luger Anna-Luisa , Schulte Dorothea , Mittelbronn Michel , Alekseeva Tijna , Sevenich Lisa , Harter Patrick N. , Münch Christian , Steinbach Joachim P. , Ronellenfitsch Michael W. 
Published: March 2022

AbstractAMP-activated protein kinase (AMPK) is a central cellular energy sensor that regulates metabolic activity. We hypothesised that in glioblastoma (GB), AMPK plays a pivotal role in balancing metabolism under conditions of the tumour microenvironment, which is characterised by fluctuating and often low nutrient and oxygen availability. Impairment of this network could thus interfere with tumour progression.AMPK activity was modulated genetically by CRISPR/Cas9-based double knockout (DKO) of the catalytic α1 and α2 subunits in human GB cells and effects were confirmed by pharmacological AMPK inhibition using BAY3827 and an inactive control compound in primary GB cell lines.We found that metabolic adaptation of GB cells under energy stress conditions (hypoxia, glucose deprivation) was dependent on AMPK and accordingly that, AMPK DKO cells were more vulnerable to glucose-deprivation or inhibition of glycolysis and sensitised to hypoxia-induced cell death. This effect was rescued by reexpression of the AMPK α2 subunit. Similar results were observed using the selective pharmacological AMPK inhibitor BAY3827. Mitochondrial biogenesis was regulated AMPK-dependently with a reduced mitochondrial mass and mitochondrial membrane potential in AMPK DKO GB cells. In vivo, AMPK DKO GB cells showed impaired tumour growth and tumour formation in CAM assays as well as in an orthotopic glioma mouse model.Our study highlights the importance of AMPK for GB cell adaptation towards energy depletion and emphasises the role of AMPK for tumour formation in vivo. Moreover, we identified mitochondria as central downstream effectors of AMPK signalling. The development of AMPK inhibitors could open opportunities for the treatment of hypoxic tumours.
S6K1 phosphorylates Cdk1 and MSH6 to regulate DNA repair
Authors: Amar-Schwartz Adi , Ben-Hur Vered , Jbara Amina , Cohen Yuval , Barnabas Georgina , Siegfried Zahava , Mashahreh Bayan , Hassouna Fouad , Shilo Asaf , Abu-Odeh Mohammad , Berger Michael , Wiener Reuven , Aqeilan Rami I. , Geiger Tamar , Karni Rotem 
Published: March 2022

AbstractThe mTORC1 substrate, S6 Kinase 1 (S6K1), is involved in the regulation of cell growth, ribosome biogenesis, glucose homeostasis and adipogenesis. Accumulating evidence has suggested a role for mTORC1 signaling in the DNA damage response. This is mostly based on the findings that mTORC1 inhibitors sensitized cells to DNA damage. However, a direct role of the mTORC1-S6K1 signaling pathway in DNA repair and the mechanism by which this signaling pathway regulates DNA repair is unknown. In this study, we discovered a novel role for S6K1 in regulating DNA repair through the coordinated regulation of the cell cycle, homologous recombination (HR) DNA repair (HRR) and mismatch DNA repair (MMR) mechanisms. Here we show that S6K1 orchestrates DNA repair by phosphorylation of Cdk1 at serine 39, causing G2/M cell cycle arrest enabling homologous recombination and by phosphorylation of MSH6 at serine 309, enhancing MMR. Moreover, breast cancer cells harboring RPS6KB1 gene amplification show increased resistance to several DNA damaging agents and S6K1 expression is associated with poor survival of breast cancer patients treated with chemotherapy. Our findings reveal an unexpected function of S6K1 in the DNA repair pathway, serving as a tumorigenic barrier by safeguarding genomic stability.