bluuebunny/crossref_metadata_2025_split huggingface dataset:
How can graph theory inform the dual-stream model of speech processing? a resting-state fMRI study of post-stroke aphasia
Authors: Zhu Haoze , Fitzhugh Megan C. , Keator Lynsey M. , Johnson Lisa , Rorden Chris , Bonilha Leonardo , Fridriksson Julius , Rogalsky Corianne 
Published: April 2023

AbstractThe dual-stream model of speech processing has been proposed to represent the cortical networks involved in speech comprehension and production. Although it is arguably the prominent neuroanatomical model of speech processing, it is not yet known if the dual-stream model represents actual intrinsic functional brain networks. Furthermore, it is unclear how disruptions after a stroke to the functional connectivity of the dual-stream model’s regions are related to specific types of speech production and comprehension impairments seen in aphasia. To address these questions, in the present study, we examined two independent resting-state fMRI datasets: (1) 28 neurotypical matched controls and (2) 28 chronic left-hemisphere stroke survivors with aphasia collected at another site. Structural MRI, as well as language and cognitive behavioral assessments, were collected. Using standard functional connectivity measures, we successfully identified an intrinsic resting-state network amongst the dual-stream model’s regions in the control group. We then used both standard functional connectivity analyses and graph theory approaches to determine how the functional connectivity of the dual-stream network differs in individuals with post-stroke aphasia, and how this connectivity may predict performance on clinical aphasia assessments. Our findings provide strong evidence that the dual-stream model is an intrinsic network as measured via resting-state MRI, and that weaker functional connectivity of the hub nodes of the dual-stream network defined by graph theory methods, but not overall average network connectivity, is weaker in the stroke group than in the control participants. Also, the functional connectivity of the hub nodes predicted specific types of impairments on clinical assessments. In particular, the relative strength of connectivity of the right hemisphere’s homologues of the left dorsal stream hubs to the left dorsal hubs versus right ventral stream hubs is a particularly strong predictor of post-stroke aphasia severity and symptomology.
Financial conflicts of interest between pharmaceutical companies and executive board members of internal medicine subspecialty societies in Japan between 2016 and 2020
Authors: Murayama Anju , Saito Hiroaki , Tanimoto Tetsuya , Ozaki Akihiko 
Published: April 2023

AbstractUsing payment data disclosed by 92 major pharmaceutical companies, this study evaluated personal payments to executive board members (EBMs) among each specialized field of internal medicine in Japan. A total of 63,405 personal payments worth of $70,796,014 in payment amounts were made to 99.2% of all EBMs of the 15 leading professional societies of internal medicine in Japan between 2016 and 2020.
Sensitivity of temperature-based time since death estimation on measurement location
Authors: Subramaniam J. Shanmugam , Hubig M. , Muggenthaler H. , Schenkl S. , Ullrich J. , Pourtier G. , Weiser M. , Mall G. 
Published: April 2023

AbstractRectal temperature measurement (RTM) from crime scenes is an important parameter for temperature-based time of death estimation (TDE). Various influential variables exist in TDE methods like the uncertainty in thermal and environmental parameters. Although RTM depends in particular on the location of measurement position, this relationship has never been investigated separately. The presented study fills this gap using Finite Element (FE) simulations of body cooling. A manually meshed coarse human FE model and an FE geometry model developed from the CT scan of a male corpse are used for TDE sensitivity analysis. The coarse model is considered with and without a support structure of moist soil. As there is no clear definition of ideal rectal temperature measurement location for TDE, possible variations in RTM location (RTML) are considered based on anatomy and forensic practice. The maximum variation of TDE caused by RTML changes is investigated via FE simulation. Moreover, the influence of ambient temperature, of FE model change and of the models positioning on a wet soil underground are also discussed. As a general outcome, we notice that maximum TDE deviations of up to ca. 2-3 h due to RTML deviations have to be expected. The direction of maximum influence of RTML change on TDE generally was on the line caudal to cranial.
Proximity to Boundaries Reveals Spatial Context Representation in Human Hippocampal CA1
Authors: Geva-Sagiv Maya , Dimsdale-Zucker Halle R. , Williams Ashley B. , Ranganath Charan 
Published: April 2023

AbstractRecollection of real-world events is often accompanied by a sense of being in the place where the event transpired. Convergent evidence suggests the hippocampus plays a key role in supporting episodic memory by associating information with the time and place it was originally encountered. This representation is reinstated during memory retrieval. However, little is known about the roles of different subfields of the human hippocampus in this process. Research in humans and non-human animal models have suggested that spatial environmental boundaries have a powerful influence on spatial and episodic memory, as well as hippocampal representations of contexts and events. Here, we used high-resolution fMRI to investigate how boundaries influence hippocampal activity patterns during the recollection of objects encountered in different spatial contexts. During the encoding phase, participants viewed objects once in a naturalistic virtual reality task, in which they passively explored two rooms in one of two houses. Following the encoding phase, participants were scanned while they recollected items in the absence of any spatial contextual information. Our behavioral results demonstrated that spatial context memory was enhanced for objects encountered near a boundary. Activity patterns in CA1 carried information about the spatial context associated with each of these boundary items. Exploratory analyses revealed that memory for the room in which each object was studied was correlated with the fidelity of retrieved spatial context representations in anterior parahippocampal cortex and subiculum. Our results highlight the privileged role of boundaries in CA1 and suggest more generally a close relationship between memory for spatial contexts and representations in the hippocampus and parahippocampal region.
Novel protein interaction network of human calcitonin receptor-like receptor revealed by label-free quantitative proteomics
Authors: Manolis Dimitrios , Hasan Shirin , Ettelaie Camille , Maraveyas Anthony , O’Brien Darragh P. , Kessler Benedikt M. , Kramer Holger , Nikitenko Leonid L. 
Published: April 2023

AbstractBackgroundG protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) signalling is implicated in skin-related and cardiovascular diseases, migraine and cancer. However, beyond its agonists and receptor activity-modifying proteins (RAMPs), proteins which bind to CLR and define its properties in primary human cells remain insufficiently understood.AimWe aimed to profile the CLR interactome in primary human dermal lymphatic endothelial cells (HDLEC), where this GPCR is expressed.Materials and methodsImmunoprecipitation (IP) of core- and terminally-glycosylated CLR from primaryin vitrocultured HDLEC was conducted using rabbit polyclonal anti-human CLR serum (with pre- immune serum serving as a control) and confirmed by immunoblotting. Total HDLEC and co-immunoprecipitated CLR proteomes were analysed by label-free quantitative nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). Quantitativein-situproximity ligation assay (PLA) using ZEISS LSM 710 confocal microscope and ZEN Blue 3.0 and Image J software was performed to confirm nLC-MS/MS findings. All experiments were repeated at least three times (biological replicates). For statistical analysis of PLA data, distribution was analysed using Shapiro-Wilk normality test followed by an unpairedt-test or Mann-Whitney test with ap-value of ≤0.05 interpreted as significant. For MS data of CLR IP samples, statistical analysis was performed usingt-test with a permutation-based false discovery rate (FDR)-adjustedp-value of ≤0.006 interpreted as significant.ResultsA total of 4,902 proteins were identified and quantified by nLC-MS/MS in primary HDLEC and 46 were co-immunoprecipitated with CLR (p<0.006). Direct interaction with the GPCR was confirmed for five of these by PLA (p<0.01).ConclusionsThis is the first study of its kind to identify novel binding partners of CLR expressed in primary human cells. Our integrative quantitative approach, combining immunoprecipitation of core- and terminally-glycosylated CLR, nLC-MS/MS, and PLA, could be applied in a similar fashion to study its interactome in a variety of human cells and tissues, and its contribution to a range of diseases, where the role of this GPCR is implicated.
Continuous Evaluation of Denoising Strategies in Resting-State fMRI Connectivity Using fMRIPrep and Nilearn
Authors: Wang Hao-Ting , Meisler Steven L , Sharmarke Hanad , Clarke Natasha , Gensollen Nicolas , Markiewicz Christopher J , Paugam François , Thirion Bertrand , Bellec Pierre 
Published: April 2023

AbstractReducing contributions from non-neuronal sources is a crucial step in functional magnetic resonance imaging (fMRI) connectivity analyses. Many viable strategies for denoising fMRI are used in the literature, and practitioners rely on denoising benchmarks for guidance in the selection of an appropriate choice for their study. However, fMRI denoising software is an ever-evolving field, and the benchmarks can quickly become obsolete as the techniques or implementations change. In this work, we present a denoising benchmark featuring a range of denoising strategies, datasets and evaluation metrics for connectivity analyses, based on the popular fMRIprep software. The benchmark is implemented in a fully reproducible framework, where the provided research objects enable readers to reproduce or modify core computations, as well as the figures of the article using the Jupyter Book project and the Neurolibre reproducible preprint server (https://neurolibre.org/). We demonstrate how such a reproducible benchmark can be used for continuous evaluation of research software, by comparing two versions of the fMRIprep software package. The majority of benchmark results were consistent with prior literature. Scrubbing, a technique which excludes time points with excessive motion, combined with global signal regression, is generally effective at noise removal. Scrubbing however disrupts the continuous sampling of brain images and is incompatible with some statistical analyses, e.g. auto-regressive modeling. In this case, a simple strategy using motion parameters, average activity in select brain compartments, and global signal regression should be preferred. Importantly, we found that certain denoising strategies behave inconsistently across datasets and/or versions of fMRIPrep, or had a different behavior than in previously published benchmarks. This work will hopefully provide useful guidelines for the fMRIprep users community, and highlight the importance of continuous evaluation of research methods. Our reproducible benchmark infrastructure will facilitate such continuous evaluation in the future, and may also be applied broadly to different tools or even research fields.
Kinetic investigation reveals an HIV-1 Nef-dependent increase in AP-2 recruitment and productivity at endocytic sites
Authors: Iwamoto Yuichiro , Ye Anna , Shirazinejad Cyna , Hurley James H. , Drubin David G. 
Published: April 2023

AbstractLentiviruses express non-enzymatic accessory proteins whose function is to subvert cellular machinery in the infected host. The HIV-1 accessory protein Nef hijacks clathrin adaptors to degrade or mislocalize host proteins involved in antiviral defenses. Here, we investigate the interaction between Nef and clathrin-mediated endocytosis (CME), a major pathway for membrane protein internalization in mammalian cells, using quantitative live-cell microscopy in genome-edited Jurkat cells. Nef is recruited to CME sites on the plasma membrane, and this recruitment correlates with an increase in the recruitment and lifetime of CME coat protein AP-2 and late-arriving CME protein dynamin2. Furthermore, we find that CME sites that recruit Nef are more likely to recruit dynamin2, suggesting that Nef recruitment to CME sites promotes CME site maturation to ensure high efficiency in host protein downregulation.
Comparative analysis of twoCaenorhabditis eleganskinesins KLP-6 and UNC-104 reveals a common and distinct activation mechanism in kinesin-3
Authors: Kita Tomoki , Chiba Kyoko , Wang Jiye , Nakagawa Atsushi , Niwa Shinsuke 
Published: April 2023

AbstractKinesin-3 is a family of microtubule-dependent motor proteins that transport various cargos within the cell. However, the mechanism underlying kinesin-3 activations remains largely elusive. In this study, we compared the biochemical properties of twoCaenorhabditis eleganskinesin-3 family proteins, KLP-6 and UNC-104. Both KLP-6 and UNC-104 are predominantly monomeric in solution. As previously shown for UNC-104, non-processive KLP-6 monomer is converted to a processive motor when artificially dimerized. We present evidence that releasing the autoinhibition is sufficient to trigger dimerization of monomeric UNC-104 at nanomolar concentrations, which results in processive movement of UNC-104 on microtubules, although it has long been thought that enrichment in the phospholipid microdomain on cargo vesicles is required for the dimerization and processive movement of UNC-104. In contrast, KLP-6 remains to be a non-processive monomer even when its autoinhibition is unlocked, suggesting a requirement of other factors for full activation. By examining the differences between KLP-6 and UNC-104, we identified a coiled-coil domain called CC2 that is required for the efficient dimerization and processive movement of UNC-104. Our results suggest a common activation mechanism for kinesin-3 family members, while also highlighting their diversification.
BrainTACO: An Explorable Multi-Scale Multi-Modal Brain Transcriptomic And Connectivity Data Resource
Authors: Ganglberger Florian , Toepfer Markus , Kargl Dominic , Hernandez-Lallement Julien , Lawless Nathan , Fernandez-Albert Francesc , Haubensak Wulf , Bühler Katja 
Published: April 2023

AbstractExploring the relationships between genes, brain circuitry, and behaviour is accelerated by the joint analysis of a heterogeneous sets form 3D imaging data, anatomical data, and brain networks at varying scales, res-olutions, and modalities. Hence, generating an integrated view, beyond the individual resources’ original purpose, requires the fusion of these data to a common space, and a visualization that bridges the gap across scales. However, despite ever expanding datasets, few plat-forms for integration and exploration of this heterogeneous data exist. To this end, we present theBrainTACO(Brain Transcriptomic And Connectivity Data) resource, a selection of heterogeneous, and multi-scale neurobiological data spatially mapped onto a common, hierarchical reference space, combined via a holistic data integration scheme. To accessBrainTACO, we extendedBrainTrawler, a web-based visual ana-lytics framework for spatial neurobiological data, with comparative visualizations of multiple resources for gene expression dissection of brain networks with an unprecedented coverage. Using this platform, allows to straightforward explore and extract brain data for identifying potential genetic drivers of connectivity in both mice and humans that may contribute to the discovery of dysconnectivity phenotypes. Hence,BrainTACOreduces the need for time-consuming manual data aggregation often required for computational analyses in script based toolboxes, and supports neuroscientists by focusing on leveraging the data instead of preparing it.
Genomic evidence of genuine wild versus admixed olive populations evolving in the same natural environments in western Mediterranean Basin
Authors: Zunino Lison , Cubry Philippe , Sarah Gautier , Mournet Pierre , Bakkali Ahmed El , Aqbouch Laila , Costes Evelyne , Khadari Bouchaib 
Published: April 2023

AbstractAdmixtures between wild animals and plants and their domesticated relatives are widely documented. This can have positive or negative impacts on the evolution of admixed populations in natural environments, yet the phenomenon is still misunderstood in long-lived woody species, contrary to short-lived crops. Wild oliveOlea europaeaL. occurs in the same eco-geographical range as domesticated olive, i.e. the Mediterranean Basin (MB). Moreover, it is an allogamous and anemophilous species whose seeds are disseminated by birds, i.e. factors that drive gene flow between crops and their wild relatives. Here we investigated the genetic structure of western MB wild olive populations in natural environments assuming a homogenous gene pool with limited impact of cultivated alleles, as previously suggested. We used a target sequencing method based on annotated genes from the Farga reference genome to analyze 27 western MB olive tree populations sampled in natural environments in France, Spain and Morocco. We also target sequenced cultivated olive tree accessions from the Worldwide Olive Germplasm Bank of Marrakech and Porquerolles and from an eastern MB wild olive tree population. We combined PCA, sNMF, pairwise Fst and TreeMix and clearly identified genuine wild olive trees throughout their natural distribution range along a north-south gradient including, for the first time, in southern France. However, contrary to our assumption, we highlighted more admixed than genuine wild olive trees. Our results raise questions regarding the admixed population evolution pattern in this environment, which might be facilitated by crop-to-wild gene flow.
YACHT: an ANI-based statistical test to detect microbial presence/absence in a metagenomic sample
Authors: Koslicki David , White Stephen , Ma Chunyu , Novikov Alexei 
Published: April 2023

AbstractIn metagenomics, the study of environmentally associated microbial communities from their sampled DNA, one of the most fundamental computational tasks is that of determining which genomes from a reference database are present or absent in a given sample metagenome. While tools exist to answer this question, all existing approaches to date return point estimates, with no associated confidence or uncertainty associated with it. This has led to practitioners experiencing difficulty when interpreting the results from these tools, particularly for low abundance organisms as these often reside in the “noisy tail” of incorrect predictions. Furthermore, no tools to date account for the fact that reference databases are often incomplete and rarely, if ever, contain exact replicas of genomes present in an environmentally derived metagenome. In this work, we present solutions for these issues by introducing the algorithmYACHT:Yes/NoAnswers toCommunity membership viaHypothesisTesting. This approach introduces a statistical framework that accounts for sequence divergence between the reference and sample genomes, in terms of average nucleotide identity, as well as incomplete sequencing depth, thus providing a hypothesis test for determining the presence or absence of a reference genome in a sample. After introducing our approach, we quantify its statistical power as well as quantify theoretically how this changes with varying parameters. Subsequently, we perform extensive experiments using both simulated and real data to confirm the accuracy and scalability of this approach. Code implementing this approach, as well as all experiments performed, is available athttps://github.com/KoslickiLab/YACHT.
Evolution of ancient satellite DNAs in extant alligators and caimans (Crocodylia, Reptilia)
Authors: Sales-Oliveira Vanessa C. , dos Santos Rodrigo Zeni , Goes Caio Augusto Gomes , Calegari Rodrigo Milan , Garrido-Ramos Manuel A. , Altmanová Marie , Ezaz Tariq , Liehr Thomas , Porto-Foresti Fabio , Utsunomia Ricardo , Cioffi Marcelo de Bello 
Published: April 2023

AbstractCrocodilians are one of the oldest extant vertebrate lineages, which exhibits a combination of evolutionary success and morphological resilience that have persisted throughout the history of life on Earth. Such an ability to endure over such a long geological time span is of great evolutionary importance. Here, we performed a comprehensive analysis of the satellite DNA diversity of the extant alligators and caimans, making significant progress in our understanding of the evolution of repetitive regions present in ancient genomes. The alligators and caimans displayed a small number of satDNA families (varying between 3 and 13 satDNAs, inA. sinensisandC. latirostris, respectively) as well as little variation both within and between species, highlighting an exceptional long-term conservation of satDNA elements throughout evolution. We also tracked the origin of the ancestral forms of all satDNAs belonging to the common ancestor of Caimaninae and Alligatoridae. Fluorescence in situ experiments showed distinct hybridization patterns for the identical ortholog satDNAs, indicating their inner dynamic evolution. Why, in addition to their previously known low genetic, karyotype, and morphological diversity, have crocodilians altered so little over such a long period of time with such a highly variable genome fraction? We argued that such an “evolutionary package” was likely the outcome of severe demographic declines or founder events and that it represents evolutionary responses to a long-lasting bottleneck history.
Grubraw, a chemogenetic mitochondrial activator, reveals new mechanisms underlying the Warburg effect
Authors: Potekhina Ekaterina S. , Bass Dina Y. , Ivanenko Alexander V. , Moshchenko Alexander A. , Korzhenevskiy Dmitri A. , Shevchenko Evgeniy , Karnaeva Anastasia E. , Zakirova Natalia F. , Ivanov Alexander V. , Shimolina Liubov E. , Shirmanova Marina V. , Lyang Olga V. , Patsap Olga I. , Kudryashova Olga M. , Gazizova Guzel R. , Shagimardanova Elena I. , Gusev Oleg A. , Bogeski Ivan , Nesterenko Alexey M. , Belousov Vsevolod V. 
Published: April 2023

AbstractUpregulation of glycolysis and downregulation of mitochondrial oxidative phosphorylation, termed as the Warburg effect, are characteristic of tumor cells1,2. Restriction of pyruvate flux into the mitochondrial matrix is one of the major mechanisms underlying this phenomenon3. Warburg-type metabolism is beneficial for rapidly proliferating cells, however its function remains unclear. Moreover, it is unknown what the metabolic consequences of activation of mitochondrial respiration in Warburg-type cancer cells are. Here we created a chemogenetic instrument, Grubraw, that generates pyruvate directly in the mitochondrial matrix bypassing restricted pyruvate influx. In cancer cells, Grubraw-driven pyruvate synthesis in the matrix increased mitochondrial membrane potential, oxygen consumption rate, and the amounts of TCA cycle intermediates. In a mouse model of human melanoma xenografts, chemogenetic activation of mitochondria caused a decrease in tumor growth rate. Surprisingly, cancer cells actively exported pyruvate generated by Grubraw in the mitochondria into the extracellular medium. In addition, activation of mitochondria induced downregulation of transcription of the genes that drive cell cycle progression, cell proliferation and DNA replication. Our results demonstrate that cells with Warburg-type metabolism use previously unknown mechanisms of carbon flux control to dispose of excessive mitochondrial pyruvate, and activation of mitochondria in these cells downregulates cellular proliferation.