bluuebunny/crossref_metadata_2025_split huggingface dataset:
7 Tesla MRS estimates of GABA concentration relate to physiological measures of tonic inhibition in the human motor cortex
Authors: Paparella Ilenia , Cardone Paolo , Zanichelli Benedetta , Lamalle Laurent , Collette Fabienne , Sherif Siya , Zubkov Mikhail , Clarke William T , Stagg Charlotte J , Maquet Pierre , Vandewalle Gilles 
Published: July 2024

AbstractGABAergic neurotransmission within the cortex plays a key role in learning and is altered in several brain diseases. Quantification of bulk GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. A recent mathematical simulation contends that MRS detects extrasynaptic GABA, mediating tonic inhibition. Nevertheless, no empirical data have yet confirmed this hypothesis. Here we collected ultra-high field 7 Tesla MRS and Transcranial Magnetic Stimulation coupled with high-density Electroencephalography (TMS-hdEEG) from the motor cortex of twenty healthy participants (age 23.95±6.4), while they were at rest. We first applied a Neural Mass Model to TMS-evoked potentials to disentangle the contribution of different GABAergic pools. We then assessed to which of these different pools MRS-GABA was related to by means of Parametric Empirical Bayesian (PEB) analysis. We found that MRS-GABA was mostly positively related to the NMM-derived measures of tonic inhibition and overall functionality of the GABAergic synapse. This relationship was reliable enough to predict MRS-GABA from NMM-GABA. These findings clarify the mesoscopic underpinnings of GABA levels measured by MRS and will contribute to the concretization of MRS-GABA promises to improve our understanding of human behaviour, brain physiology and pathophysiology.Key pointsGABA neurotransmission is essential for synaptic plasticity and learning (especially motor learning) and is altered in several brain disorders, such as epilepsy and stroke.Quantification of GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated.By using a biophysical Neural Mass Model, here we show that MRS-GABA relates to physiological measures of tonic inhibition in the human cortex.
Assembling a true ‘Olympic Gel’ from >16,000 combinatorial DNA rings
Authors: Speed Sarah , Atabay Azra , Peng Yu-Hsuan , Gupta Krishna , Müller Toni , Fischer Carolin , Sommer Jens-Uwe , Lang Michael , Krieg Elisha 
Published: July 2024

AbstractOlympic gels are an elusive form of soft matter, comprising a three-dimensional network of mechanically interlocked cyclic molecules. In the absence of defined network junctions, the high conformational freedom of the molecules was previously theorized to confer unique mechanical properties to Olympic gels, such as non-linear elasticity and unconventional swelling characteristics. However, the synthesis of an Olympic gel exhibiting these intriguing features is challenging, since unintended crosslinking and polymerization processes are often favored over cyclization. Here, we report the successful assembly of a true Olympic gel from a library of DNA rings comprising more than 16,000 distinct molecules. Each of these rings contains a unique sequence domain that can be enzymatically activated to produce reactive termini that favor intramolecular cyclization. We characterized the material’s genetic, mechanical, and structural characteristics by next-generation sequencing, oscillatory rheology, large-scale computational simulations, atomic force microscopy, and cryogenic electron microscopy. Our results confirm the formation of a stable Olympic gel, which exhibits unique swelling behavior and an elastic response that is exclusively determined by entanglements, yet persists on long time scales. By combining concepts from polymer physics, synthetic biology, and DNA nanotechnology, this new material class provides a flexible experimental platform for future studies into the effects of network topology on macroscopic material properties and its function as a carrier of genetic information in biological and biomimetic systems. This work moreover demonstrates that exotic material properties can emerge in systems with a high compositional complexity that is more reminiscent of biological than synthetic matter.Abstract Figure
CELLNET technology: Spatially organized, functional 3D networks at single cell resolution
Authors: Poudel Arun , Kunwar Puskal , Aryal Ujjwal , Merife Anna-Blessing , Soman Pranav 
Published: July 2024

AbstractCells possess the remarkable ability to generate tissue-specific 3D interconnected networks and respond to a wide range of stimuli. Understanding the link between the spatial arrangement of individual cells and their networks’ emergent properties is necessary for the discovery of both fundamental biology as well as applied therapeutics. However, current methods spanning from lithography to 3D photo-patterning to acoustofluidic devices are unable to generate interconnected and organized single cell 3D networks within native extracellular matrix (ECM). To address this challenge, we report a novel technology coined as CELLNET. This involves the generation of crosslinked collagen within multi-chambered microfluidic devices followed by femtosecond laser ablation of 3D microchannel networks and cell seeding. Using model cells, we show that cell migrate within ablated networks within hours, self-organize and form viable, interconnected, 3D networks in custom architectures such as square grid, concentric circle, parallel lines, and spiral patterns. Heterotypic CELLNETs can also be generated by seeding multiple cell types in side-chambers of the devices. The functionality of cell networks can be studied by monitoring the real-time calcium signaling response of individual cells and signal propagation within CELLNETs when subjected to flow stimulus alone or a sequential combination of flow and biochemical stimuli. Furthermore, user-defined disrupted CELLNETs can be generated by lethally injuring target cells within the 3D network and analyzing the changes in their signaling dynamics. As compared to the current self-assembly based methods that exhibit high variability and poor reproducibility, CELLNETs can generate organized 3D single-cell networks and their real-time signaling responses to a range of stimuli can be accurately captured using simple cell seeding and easy-to-handle microfluidic devices. CELLNET, a new technology agnostic of cell types, ECM formulations, 3D cell-connectivity designs, or location and timing of network disruptions, could pave the way to address a range of fundamental and applied bioscience applications.TeaserNew technology to generate 3D single cell interconnected and disrupted networks within natural extracellular matrix in custom configurations.
Follicle stimulating hormone receptor expression in human pancreas and effects on insulin secretion: A translational study
Authors: Aydin Banu Kucukemre , Incedal Nilsson Ceren , Chowdhury Azazul , Wen Quan , Cerenius Sara Y. , Stenlid Rasmus , Mörwald Katharina , Ciba Iris , Manell Hannes , Weghuber Daniel , Forslund Anders , Idevall-Hagren Olof , Bergsten Peter 
Published: July 2024

SummaryFollicle-stimulating hormone (FSH) is traditionally known for its role in reproduction, but recent studies suggest it may also influence metabolic processes. This study aimed to examine FSH receptor (FSHR) expression in human pancreatic islets and the direct effects of FSH on insulin secretion, as well as explore FSH’s metabolic role during puberty, focusing on enhanced insulin secretion during this critical period. FSHR gene and protein expression were detected in isolated human pancreatic islets and co-localized with insulin-producing beta-cells. Additionally, FSH at prepubertal (0.1 IU/L) and pubertal concentrations (10 IU/L) significantly enhanced glucose-stimulated insulin secretion (GSIS) and increased intracellular cAMP concentrations in intact human pancreatic islets. In children with obesity from the Beta-JUDO cohort (n=608), plasma FSH levels were positively associated with several insulin secretion indices, particularly in pubertal children. These findings suggest that FSH has significant metabolic roles beyond reproduction, involving insulin secretion and potentially contributing to puberty-related hyperinsulinemia and insulin resistance.
Nitrogen sharing strategies in six clonal species
Authors: Duchoslavová Jana 
Published: July 2024

AbstractNitrogen is often a limiting factor for plant growth, and its availability is a major determinant of level of competition. In clonal plants, patterns of nitrogen translocation between ramets may be part of plant nitrogen economics, and, as such, may also be related to the typical availability of nitrogen. In nutrient-poor habitats, extensive nutrient sharing balancing resource availability may be important, whereas nutrient sharing between established ramets may not be beneficial in productive habitats.I tested the proposed nutrient sharing strategies on nitrogen translocation in six stoloniferous species that occur in habitats of varying productivity. Mother and daughter ramets of each species were grown either in a homogeneous nutrient-poor treatment or in a “nutrient-poor to nutrient-rich” treatment. I traced the translocation of nitrogen in both directions using stable isotope labelling when the daughter ramets were one month old.Surprisingly, I found no effect of nutrient treatment on nitrogen translocation. Instead, each species translocated nitrogen either acropetally, basipetally, or equally in both directions. There was no relationship between the direction of translocation and the productivity of the species’ habitats. However, net translocation seemed to be related to the relative size of daughters across species, and withinVeronica officinalis.The results suggest that the relative size of plant parts is an important determinant of the strength of the sink for nitrogen they form, and that the growth habit of a species can affect its nitrogen translocation. Under certain conditions, such internally induced source-sink relationships may dominate over external nitrogen heterogeneity. I speculate that growth habit, together with nitrogen translocation patterns, may be part of adaptive growth strategies.
ProtParts, an automated web server for clustering and partitioning protein dataset
Authors: Li Yuchen , Barra Carolina 
Published: July 2024

ABSTRACTData leakage originating from protein sequence similarity shared among train and test sets can result in model overfitting and overestimation of model performance and utility. However, leakage is often subtle and might be difficult to eliminate. Available clustering tools often do not provide completely independent partitions, and in addition it is difficult to assess the statistical significance of those differences. In this study, we developed a clustering and partitioning tool, ProtParts, utilizing the E-value of BLAST to compute pairwise similarities between each pair of proteins and using a graph algorithm to generate clusters of similar sequences. This exhaustive clustering ensures the most independent partitions, giving a metric of statistical significance and, thereby enhancing the model generalization. A series of comparative analyses indicated that ProtParts clusters have higher silhouette coefficient and adjusted mutual information than other algorithms using k-mers or sequence percentage identity. Re-training three distinct predictive models revealed how sub-optimal data clustering and partitioning leads to overfitting and inflated performance during cross-validation. In contrast, training on ProtParts partitions demonstrated a more robust and improved model performance on predicting independent data. Based on these results, we deployed the user-friendly web server ProtParts (https://services.healthtech.dtu.dk/services/ProtParts-1.0) for protein partitioning prior to machine learning applications.GRAPHICAL ABSTRACT
Effects of N361 Glycosylation on Epidermal Growth Factor Receptor Biological Function
Authors: Lam Dennis , Arroyo Brandon , Liberchuk Ariel N. , Wolfe Andrew L. 
Published: July 2024

ABSTRACTEpidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase that is frequently modified by glycosylation post-translationally. In cancer, EGFR amplifications and hotspot mutations such as L858R that promote proliferation have been detected in a significant fraction of non-small cell lung carcinomas and breast adenocarcinomas. Molecular dynamic simulations suggested that glycosylation at asparagine residue 361 (N361) promotes dimerization and ligand binding. We stably expressed glycosylation-deficient mutant EGFR N361A, with or without the oncogenic mutation L858R. Immunofluorescence and flow cytometry demonstrated that the mutants were each well expressed at the cell membrane. N361A decreased proliferation relative to wild-type EGFR as well as decreased sensitivity to ligands. Proximity ligation assays measuring co-localization of EGFR with its binding partner HER2 in cells revealed that N361A mutations increased co-localization. N361A, located near the binding interface for the EGFR inhibitor necitumumab, desensitized cells expressing the oncogenic EGFR L858R to antibody-based inhibition. These findings underline the critical relevance of post-translational modifications on oncogene function.SIGNIFICANCEEGFR transduces signals from growth factors into cell proliferation and is frequently hyperactivated in tumors. Glycosylation of EGFR at N361 regulates EGFR dimerization, growth factor stimulation of proliferative signaling, and susceptibility to targeted inhibition. Insights into EGFR glycosylation may expand therapeutic opportunities to benefit cancer patients.
Cells in the Polyaneuploid Cancer Cell State are Pro-Metastatic
Authors: Mallin Mikaela M. , Rolle Louis T.A. , Schmidt Michael J. , Priyadarsini Nair Shilpa , Zurita Amado J. , Kuhn Peter , Hicks James , Pienta Kenneth J. , Amend Sarah R. 
Published: July 2024

AbstractThere remains a large need for a greater understanding of the metastatic process within the prostate cancer field. Our research aims to understand the adaptive – ergo potentially metastatic – responses of cancer to changing microenvironments. Emerging evidence has implicated a role of the Polyaneuploid Cancer Cell (PACC) state in metastasis, positing the PACC state as capable of conferring metastatic competency. Mountingin vitroevidence supports increased metastatic potential of cells in the PACC state. Additionally, our recent retrospective study of prostate cancer patients revealed that PACC presence in the prostate at the time of radical prostatectomy was predictive of future metastatic progression. To test for a causative relationship between PACC state biology and metastasis, we leveraged a novel method designed for flow-cytometric detection of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in subcutaneous, caudal artery, and intracardiac mouse models of metastasis. This approach provides both quantitative and qualitative information about the number and PACC-status of recovered CTCs and DTCs. Collating data from all models, we found that 74% of recovered CTCs and DTCs were in the PACC state.In vivocolonization assays proved PACC populations can regain proliferative capacity at metastatic sites following dormancy. Additional direct and indirect mechanisticin vitroanalyses revealed a PACC-specific partial Epithelial-to-Mesenchymal-Transition phenotype and a pro-metastatic secretory profile, together providing preliminary evidence that PACCs are mechanistically linked to metastasis.Statement of SignificanceWe provide the first evidence that cells in the polyaneuploid cancer cell state contribute to increased metastatic competencyin vivo.
A SMARTTR workflow for multi-ensemble atlas mapping and brain-wide network analysis
Authors: Jin Michelle , Ogundare Simon O. , Lanio Marcos , Sorid Sophia , Whye Alicia R. , Santos Sofia Leal , Franceschini Alessandra , Denny Christine. A. 
Published: July 2024

AbstractIn the last decade, activity-dependent strategies for labelling multiple immediate early gene (IEG) ensembles in mice have generated unprecedented insight into the mechanisms of memory encoding, storage, and retrieval. However, few strategies exist for brain-wide mapping of multiple ensembles, including their overlapping population, and none incorporate capabilities for downstream network analysis. Here, we introduce a scalable workflow to analyze traditionally coronally-sectioned datasets produced by activity-dependent tagging systems. Intrinsic to this pipeline issimplemulti-ensembleatlasregistration and statisticaltesting inR(SMARTTR), an R package which wraps mapping capabilities with functions for statistical analysis and network visualization, and support for import of external datasets. We demonstrate the versatility of SMARTTR by mapping the ensembles underlying the acquisition and expression of learned helplessness (LH), a robust stress model. Applying network analysis, we find that exposure to inescapable shock (IS), compared to context training (CT), results in decreased centrality of regions engaged in spatial and contextual processing and higher influence of regions involved in somatosensory and affective processing. During LH expression, the substantia nigra emerges as a highly influential region which shows a functional reversal following IS, indicating a possible regulatory function of motor activity during helplessness. We also report that IS results in a robust decrease in reactivation activity across a number of cortical, hippocampal, and amygdalar regions, indicating suppression of ensemble reactivation may be a neurobiological signature of LH. These results highlight the emergent insights uniquely garnered by applying our analysis approach to multiple ensemble datasets and demonstrate the strength of our workflow as a hypothesis-generating toolkit.
The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination
Authors: Smethells JR , Wilde S , Muelken P , LeSage MG , Harris AP 
Published: July 2024

AbstractBackgroundβ-Nicotyrine (β-Nic) is a unique minor alkaloid constituent in electronic nicotine delivery systems (ENDS) that is derived from nicotine (Nic) degradation and can reach 25% of Nic concentrations in ENDS aerosol. β-Nic slows Nic metabolism and prolongs systemic Nic exposure, which may alter the discriminability of Nic. The present study sought to examine β-Nic has interoceptive effects itself, and if it alters the subjective effects ENDS products within a drug-discrimination paradigm.MethodsThe pharmacodynamics of β-Nic were examined in vitro, and a nicotine discrimination paradigm was used to determine if β-Nic (0 – 5.0 mg/kg) shares discriminative stimulus properties with Nic (0.2 mg/kg) in male (n = 13) and female (n = 14) rats after 10- & 60-min β-Nic pretreatment delays. A second group of rats was trained to discriminate β-Nic and Nornicotine (Nornic) from saline to determine if β-Nic alone has interoceptive properties and whether they are similar to Nornic.Resultsβ-Nic had similar binding affinity and efficacy at the α4β2 nicotinic receptor subtype as Nornic, ∼50% of Nic efficacy. However, β-Nic only weakly substituted for Nic during substitution testing in female rats, but not males, whereas Nornic fully substituted for Nic. Combination testing at the 10 and 60-min pretreatment intervals showed that β-Nic dose-dependently increased the duration of nicotine’s discriminative stimulus effects, especially at the 60-min delay. Drug naïve rats could reliably discriminate Nornic, but not β-Nic, from Sal.Conclusionβ-Nic increased and prolonged the interoceptive stimulus properties of Nic, suggesting it may alter to the abuse liability of ENDS through its ability to slow Nic metabolism.
Scales of marine endemism in oceanic islands and the Provincial-Island endemism
Authors: Pinheiro Hudson T. , Rocha Luiz A. , Quimbayo Juan P. 
Published: July 2024

AbstractOceanic islands are remote environments commonly harboring endemic species, which often are unique lineages originated and maintained by a variety of ecological, biogeographical and evolutionary processes. Endemic species are found mostly in a single oceanic island or archipelago, however, a great number of species can be considered multiple-island endemics, i.e. species found on multiple oceanic islands that still have a restricted distribution. The geographic criteria chosen to classify endemic species has a direct impact on the endemism rate of islands, and many studies have used multiple scales of endemism (single and multiple-island endemics), which has historically influenced wide-scale comparisons. In this perspective, we accessed the importance of single and multiple-island endemic species to the biodiversity of oceanic islands, introducing the concept of Provincial-island endemism as an additional strategy to standardize biogeography studies.
Enhanced sensitivity of TAPscan v4 enables comprehensive analysis of streptophyte transcription factor evolution
Authors: Petroll Romy , Varshney Deepti , Hiltemann Saskia , Finke Hermann , Schreiber Mona , de Vries Jan , Rensing Stefan A. 
Published: July 2024

SummaryTranscription associated proteins (TAPs) fulfill multiple functions in regulatory and developmental processes and display lineage-specific evolution. TAPscan is a comprehensive and highly reliable tool for genome-wide TAP annotation via domain profiles. Here, we present TAPscan v4, including an updated web interface (https://tapscan.plantcode.cup.uni-freiburg.de/), which enables an in-depth representation of the distribution of 138 TAP families across 678 species from diverse groups of organisms, with a focus on Archaeplastida (plants in the wide sense). With this release, we also make the underlying “Genome Zoo” available, a curated protein data set with scripts and metadata. 18 new TAP (sub)families were added as part of the update. Nine of those were gained in the most recent common ancestor of the Streptophyta (comprising streptophyte algae and land plants), or within the streptophyte algae. More than one-third of all detected TAP family gains were identified during the evolution of streptophyte algae, before the emergence of land plants, and are thus likely to have been significant for plant terrestrialization. The TAP complement of the Zygnematophyceae was identified to be the most similar to that of land plants, consistent with the finding that this lineage is sister to land plants. Overall, our data retrace the evolution of streptophyte TAPs, allowing us to pinpoint the regulatory repertoire of the earliest land plants.