bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exhaustive identification of genome-wide binding events of transcriptional regulators with ICEBERG
Authors: Nordin Anna , Pagella Pierfrancesco , Zambanini Gianluca , Cantù Claudio 
Published: July 2023

AbstractGenome-wide protein interaction assays aspire to map the complete binding pattern of gene regulators. How-ever, common practice relies on replication and high stringency statistics which favor false negatives over false positives, thereby excluding portions of signal which may represent biologically relevant events. Here, we present ICEBERG (Increased Capture of Enrichment By Exhaustive Replicate aGgregation), an experimental and analytical pipeline that harnesses large numbers of CUT&RUN replicates to discover the full set of binding events and chart the line between false positives and false negatives. We employed ICEBERG to map the full set of H3K4me3-marked regulatory regions and β-catenin targets in human colorectal cancer cells. The ICE-BERG datasets allow benchmarking of individual replicates, comparison of the performance of peak calling and replication approaches and expose the arbitrary nature of other strategies to identify reproducible peaks. Instead of a static view of genomic targets, ICEBERG established a spectrum of detection probabilities across the genome for a given factor, underlying the intrinsic dynamicity of its mechanism of action, and permitting to distinguish frequent from rare regulation events. Finally, ICEBERG discovered instances, undetectable with other approaches, that might underlie novel mechanisms of colorectal cancer progression.
Diagnosis of planktonic trophic network dynamics with sharp qualitative changes
Authors: Gaucherel Cedric , Fayolle Stolian , Savelli Raphael , Philippine Olivier , Pommereau Franck , Dupuy Christine 
Published: July 2023

AbstractTrophic interaction networks are notoriously difficult to understand and to diagnose (i.e., to identify contrasted network functioning regimes). Such ecological networks have many direct and indirect connections between species, and these connections are not static but often vary over time. These topological changes, as opposed to a dynamic on a static (frozen) network, can be triggered by natural forcings (e.g., seasons) and/or by human influences (e.g., nutrient or pollution inputs). Aquatic trophic networks are especially dynamic and versatile, thus suggesting new approaches for identifying network structures and functioning in a comprehensive manner.In this study, a qualitative model was devised for this purpose. Applying discrete-event models from theoretical computer science, a mechanistic and qualitative model was developed that allowed computation of the exhaustive dynamics of a given trophic network and its environment. Once the model definition is assumed, it provides all possible trajectories of the network from a chosen initial state. In a rigorous and analytical approach, for the first time, we validated the model on one theoretical and two observed trajectories recorded at freshwater stations in the La Rochelle region (Western France). The model appears to be easy to build and intuitive, and it provides additional relevant trajectories to the expert community. We hope this formal approach will open a new avenue in identifying and predicting trophic (and non-trophic) ecological networks.
Decoupled evolution of theSex Peptidegene family andSex Peptide ReceptorinDrosophilidae
Authors: Hopkins Ben R. , Angus-Henry Aidan , Kim Bernard Y. , Carlisle Jolie A. , Thompson Ammon , Kopp Artyom 
Published: July 2023

AbstractAcross internally fertilising species, males transfer ejaculate proteins that trigger wide-ranging changes in female behaviour and physiology. Much theory has been developed to explore the drivers of ejaculate protein evolution. The accelerating availability of high-quality genomes now allows us to test how these proteins are evolving at fine taxonomic scales. Here, we use genomes from 264 species to chart the evolutionary history of Sex Peptide (SP), a potent regulator of female post-mating responses inDrosophila melanogaster. We infer thatSPfirst evolved in theDrosophilinaesubfamily and has followed markedly different evolutionary trajectories in different lineages. Outside of theSophophora-Lordiphosa,SPexists largely as a single-copy gene with independent losses in several lineages. Within theSophophora-Lordiphosa,theSPgene family has repeatedly and independently expanded. Up to seven copies, collectively displaying extensive sequence variation, are present in some species. Despite these changes,SPexpression remains restricted to the male reproductive tract. Alongside, we document considerable interspecific variation in the presence and morphology of seminal microcarriers that, despite the critical role SP plays in microcarrier assembly inD. melanogaster, appear to be independent of changes in the presence/absence or sequence of SP. We end by providing evidence that SP’s evolution is decoupled from that of its receptor, SPR, in which we detect no evidence of correlated diversifying selection. Collectively, our work describes the divergent evolutionary trajectories that a novel gene has taken following its origin and finds a surprisingly weak coevolutionary signal between a supposedly sexually antagonistic protein and its receptor.SignificanceIn insects, seminal fluid proteins (SFPs) induce dramatic changes in female behaviour and physiology. How this degree of male influence evolves remains a central question in sexual selection research. Here, we map the origin and diversification of the posterchild insect SFP, theDrosophilaSex Peptide (SP), across 264 Diptera species. We show thatSPfirst evolved at the base of the subfamilyDrosophilinaeand followed markedly different evolutionary trajectories in different lineages, including accelerated change in sequence, copy number, and genomic position in the lineage leading toD. melanogaster.By contrast, we find only limited, uncorrelated change in the sequence of its receptor, SPR, arguing against a sexually antagonistic coevolutionary arms race between these loci on macroevolutionary time scales.
Exploring the Potential of Large Language Models in Personalized Diabetes Treatment Strategies
Authors: Yang Hao , Li Jiaxi , Liu Siru , Du Lei , Liu Xiali , Huang Yong , Shi Qingke , Liu Jialin 
Published: July 2023

AbstractThis study aims to explore the application of a fine-tuned model-based outpatient treatment support system for the treatment of patients with diabetes, and evaluate its effectiveness and potential value.MethodsThe ChatGLM model was selected as the subject of investigation and trained using the P-tuning and LoRA fine-tuning methods. Subsequently, the fine-tuned model was successfully integrated into the Hospital Information System (HIS). The system generates personalized treatment recommendations, laboratory test suggestions, and medication prompts based on patients’ basic information, chief complaints, medical history, and diagnosis data.ResultsExperimental testing revealed that the fine-tuned ChatGLM model is capable of generating accurate treatment recommendations based on patient information, while providing appropriate laboratory test suggestions and medication prompts. However, for patients with complex medical records, the model’s outputs may carry certain risks and cannot fully substitute outpatient physicians’ clinical judgment and decision-making abilities. The model’s input data is confined to electronic health record (EHR), limiting the ability to comprehensively reconstruct the patient’s treatment process and occasionally leading to misjudgments of the patient’s treatment goals.ConclusionThis study demonstrates the potential of the fine-tuned ChatGLM model in assisting the treatment of patients with diabetes, providing reference recommendations to healthcare professionals to enhance work efficiency and quality. However, further improvements and optimizations are still required, particularly regarding medication therapy and the model’s adaptability.
Time is of the essence: A general framework for uncovering temporal structures of communities
Authors: Yin Hannah , Rudolf Volker H. W. 
Published: July 2023

AbstractEcological communities are inherently dynamic: species constantly turn over within years, months, weeks, or even days. These temporal shifts in community composition determine essential aspects of species interactions and how energy, nutrients, information, diseases, and perturbations "flow" through systems. Yet, our understanding of community structure has relied heavily on static analyses not designed to capture critical features of this dynamic temporal dimension of communities. Here, we propose a conceptual and methodological framework for quantifying and analyzing this temporal dimension. Conceptually, we split the temporal structure into two definitive features, sequence and duration, and review how they are linked to key concepts in ecology. We then outline how we can capture these definitive features using perspectives and tools from temporal graph theory. We demonstrate how we can easily integrate ongoing research on phenology into this framework and highlight what new opportunities arise from this approach to answer fundamental questions in community ecology. As climate change reshuffles ecological communities worldwide, quantifying the temporal organization of communities is imperative to resolve the fundamental processes that shape natural ecosystems and predict how these systems may change in the future.
Uncovering novel roles of miR-122 in the pathophysiology of the liver: Potential interaction with NRF1 and E2F4 signaling
Authors: Paluschinski Martha , Schira-Heinen Jessica , Pellegrino Rossella , Heij Lara R. , Bednarsch Jan , Neumann Ulf P. , Longerich Thomas , Stuehler Kai , Luedde Tom , Castoldi Mirco 
Published: July 2023

AbstractMicroRNA miR-122 plays a pivotal role in liver function. Despite numerous studies investigating this miRNA, the global network of genes regulated by miR-122 and its contribution to the underlying pathophysiological mechanisms remain largely unknown. To gain a deeper understanding of miR-122 activity, we employed two complementary approaches. Firstly, through transcriptome analysis of polyribosome-bound RNAs, we discovered that miR-122 exhibits potential antagonistic effects on specific transcription factors known to be dysregulated in liver disease, including nuclear respiratory factor-1 (NRF1) and the E2F Transcription Factor 4 (E2F4). Secondly, through proteome analysis of hepatoma cell transfected with either miR-122 mimic or antagomiR we discovered changes in several proteins associated with increased malignancy. Interestingly, many of these proteins were reported to be transcriptionally regulated by NRF1 and E2F4, six of which we validated as miR-122 targets. Among these, a negative correlation was observed between miR-122 and glucose-6-phosphate dehydrogenase levels in the livers of patients with hepatitis B virus-associated hepatocellular carcinoma. This study provides novel insights into potential alterations of molecular pathway occurring at the early stages of liver disease, driven by the dysregulation of miR-122 and its associated genes.
Neural Dynamics Underlying Successful Auditory Short-Term Memory Performance
Authors: Pomper Ulrich , Curetti Lorenza Zaira , Chait Maria 
Published: July 2023

AbstractListeners often operate in complex acoustic environments, consisting of many concurrent sounds. Accurately encoding and maintaining such auditory objects in short-term memory is crucial for communication and scene analysis. Yet, the neural underpinnings of successful auditory short-term memory (ASTM) performance are currently not well understood.To elucidate this issue, we presented a novel, challenging auditory delayed match-to-sample task while recording MEG. Human participants listened to “scenes” comprising 3 concurrent tone pip streams. The task was to indicate, after a delay, whether a probe stream was present in the just-heard scene. We present three key findings: First, behavioural performance revealed faster responses in correct vs. incorrect trials as well as in ‘probe present’ vs ‘probe absent’ trials, consistent with ASTM search. Second, successful compared to unsuccessful ASTM performance was associated with a significant enhancement of event-related fields and oscillatory activity in the theta, alpha, and beta frequency ranges. This extends previous findings of an overall increase of persistent activity during short-term memory performance. Third, using distributed source modelling, we found these effects to be confined mostly to sensory areas during encoding, presumably related to ASTM contents per-se. Parietal and frontal sources then became relevant during the maintenance stage, indicating that effective STM operation also relies on ongoing inhibitory processes suppressing task irrelevant information.In summary, our results deliver a detailed account of the neural patterns that differentiate successful from unsuccessful ASTM performance in the context of a complex, multi-object auditory scene.
In vivomagnetic recording of single-neuron action potentials
Authors: Klein Frederike J. , Jendritza Patrick , Chopin Chloé , Parto-Dezfouli Mohsen , Solignac Aurélie , Fermon Claude , Pannetier-Lecoeur Myriam , Fries Pascal 
Published: July 2023

AbstractMeasuring fast neuronal signals is the domain of electrophysiology and magnetophysiology. While electrophysiology is easier to perform, magnetophysiology avoids tissue-based distortions and measures a signal with directional information. At the macroscale, magnetoencephalography (MEG) is established, and at the mesoscale, visually evoked magnetic fields have been reported. At the microscale however, while benefits of recording magnetic counterparts of electric spikes would be numerous, they are also highly challengingin vivo. Here, we combine magnetic and electric recordings of neuronal action potentials in anesthetized rats using miniaturized giant magneto-resistance (GMR) sensors. We reveal the magnetic signature of action potentials of well-isolated single units. The recorded magnetic signals showed a distinct waveform and considerable signal strength. This demonstration ofin vivomagnetic action potentials opens a wide field of possibilities to profit from the combined power of magnetic and electric recordings and thus to significantly advance the understanding of neuronal circuits.Significance statementElectrophysiological tools allow the measurement of single-neuron action potentials with high temporal resolution. Magnetophysiological measurements would add valuable information, but are particularly hard to achieve for single neurons. Established technology for non-invasive magnetic brain signal measurements can currently not be used inside living tissue. Here, we demonstrate that miniaturized magnetic sensors based on giant magneto-resistance enable the measurement of the magnetic counterpart of single-neuron action potentials in vivo. This proof-of-principle shows a way towards integrating magnetic and electric recordings in future experiments and thus to profit from the complementary information measured by the two modalities.
COVID-related anthropause highlights the impact of marine traffic on breeding little penguins
Authors: Dupuis Benjamin , Kato Akiko , Joly Nicolas , Saraux Claire , Ropert-Coudert Yan , Chiaradia Andre , Chimienti Marianna 
Published: July 2023

AbstractThe COVID-19 pandemic and its lock-down measures have resulted in periods of reduced human activity, known as anthropause. While this period was expected to be favorable for the marine ecosystem, due to a probable reduction of pollution, shipping traffic, industrial activity and fishing pressure, negative counterparts such as the increased use of disposable plastic and reduced fisheries surveillance and enforcement could counterbalance these positive effects. Simultaneously, on-land pressure due to human disturbance and tourism should have drastically decreased, potentially benefiting land-based marine breeders such as seabirds. Thus, long-term datasets became crucial to differentiate between historical trends and any evident changes resulting from the anthropause. We analyzed 11 years of data on several biological parameters of little penguins (Eudyptula minor) from the Penguin Parade ®, a popular tourist attraction at Phillip Island, Australia. We investigated the impact of anthropogenic activities on penguin behavior during the breeding season measured by (1) distribution at sea, (2) colony attendance, (3) isotopic niche (4) chick meal mass, and (5) offspring investment against shipping traffic and number of tourists. The 2020 lock-downs resulted in a near absence of tourists visiting the Penguin Parade ®, which was otherwise visited by 800,000+ visitors on average per year. However, our long-term analysis showed no effect of the presence of visitors on little penguins’ activities. Surprisingly, the anthropause did not triggered any changes in maritime traffic intensity and distribution in the region. While we found significant inter- and intra-annual variations for most parameters, we detected a negative effect of marine traffic on the foraging efficiency. Our results suggest that environmental variations have a greater influence on the breeding behavior of little penguins compared to short-term anthropause events. Our long-term dataset was key to test whether changes in anthropogenic activities affected the wildlife during the COVID-19 pandemic.Impact statementWe found that marine traffic, but not tourist presence, negatively impact the foraging and provisioning behavior of little penguins.
Adsorbing DNA to mica by cations: Influence of the valency and ion type
Authors: Ibrahim Mohd , Wenzel Christiane , Lallemang Max , Balzer Bizan N. , Schwierz Nadine 
Published: July 2023

AbstractIon-mediated attraction between DNA and mica plays a crucial role in biotechnological applications and molecular imaging. Here, we combine molecular dynamics simulations and single-molecule atomic force microscopy experiments to characterize the detachment forces of single-stranded DNA at mica surfaces mediated by the metal cations Li+, Na+, K+, Cs+, Mg2+and Ca2+. Ion specific adsorption at the mica/water interface compensates (Li+, Na+) or overcompensates (K+, Cs+, Mg2+and Ca2+) the bare negative surface charge of mica. In addition, direct and water-mediated contacts are formed between the ions, the phosphate oxygens of DNA and mica. The different contact types give rise to low and high force pathways and a broad distribution of detachment forces. Weakly hydrated ions, such as Cs+and water-mediated contacts lead to low detachment forces and a high mobility of the DNA on the surface. Direct ion-DNA or ion-surface contacts lead to significantly higher forces. The comprehensive view gained from our combined approach allows us to highlight the most promising cations for imaging in physiological conditions: K+to overcompensate the negative mica charge and induce long-ranged attractions. Mg2+and Ca2+to from a few specific and long-lived contacts to bind DNA with high affinity.
Variations in perfusion detectable in advance of microstructure in white matter aging
Authors: Robinson Tyler D. , Sun Yutong L. , Chang Paul T. H. , Gauthier Claudine J. , Chen J. Jean 
Published: July 2023

ABSTRACTOne of the most promising interventional targets for brain health is cerebral perfusion, but its link to white matter (WM) aging remains unclear. Motivated by existing literature demonstrating links between declining cortical perfusion and the development of WM hyperintensities, we posit that regional WM hypoperfusion precedes deteriorating WM integrity. Using the Human Connectome Project Aging (HCP-A) data set, we examine tract-wise associations between WM microstructural integrity (i.e. fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) and perfusion (i.e. cerebral blood flow and arterial transit time) in ten major bilateral WM tracts. Results show that tracts displaying the largest CBF decline in aging do not necessarily display the largest ATT decline, and vice versa. Moreover, significant WM perfusion-microstructure canonical correlations were found in all tracts, but the drivers of these correlations vary by both tract and sex, with female subjects demonstrating more tracts with large microstructural variations contributing to the correlations. Additionally, arterial transit time appears to be the earliest indicator of WM declines, preceding age-related microstructural differences and CBF in several tracts. This study contributes compelling evidence to the vascular hypothesis of WM degeneration, and highlights the utility of blood-flow timing as an early marker of aging.
Computational repurposing of oncology drugs through off-target drug binding interactions from pharmacological databases
Authors: Walpole Imogen , Zaman Farzana Y , Zhao Peinan , Marshall Vikki M. , Lin Frank , Thomas David M. , Shackleton Mark , Antolin Albert A. , Ameratunga Malaka 
Published: July 2023

AbstractPURPOSESystematic repurposing of approved medicine for another indication represents an attractive strategy to accelerating drug development in oncology. Herein we present a strategy of combining biomarker testing with drug repurposing to identify new treatments for patients with advanced cancer.METHODSTumours were sequenced with Illumina TruSight Oncology 500 (TSO-500) platform or the FoundationOne® CDx panel. Mutations were manually screened by two medical oncology clinicians and pathogenic mutations were categorised with reference to the literature. Variants of unknown significance were classified as potentially pathogenic if a plausible mechanism and computational prediction of pathogenicity existed. Gain of function mutations were evaluated through the repurposing databases Probe Miner, the Broad Institute Drug Repurposing Hub (Broad Institute DRH) and TOPOGRAPH. Gain of function mutations were classified as repurposing events if they were identified in Probe Miner, were not indexed in TOPOGRAPH which captures active clinical trial biomarkers and excluding mutations for which a known FDA-approved biomarker label exists. The performance of the computational repurposing approach was validated by evaluating its ability to identify known FDA-approved biomarkers. Exploratory functional analyses were performed with gene expression data and CRISPR-dependency data sourced from the DepMap portal. The total repurposable genome was identified by evaluating all possible gene-FDA drug approved combinations in the Probe Miner dataset.RESULTSThe computational repurposing approach was highly accurate at identifying FDA therapies with known biomarkers (94%). Using a real-world dataset of next-generation sequencing molecular reports (n = 94) and excluding the identification of mutations that would render patients eligible for FDA-licensed therapies or local clinical trials, it was found that a meaningful percentage of patients (14%) would have an off-label therapeutic identified through this approach. Exploratory analyses were performed, including the identification of drug-target interactions that have been previously described in the medicinal chemistry literature but are not well known, and the evaluation of the frequency of theoretical drug repurposing events in the TCGA pan-cancer dataset (73% of samples in the cohort).CONCLUSIONOverall, a computational drug repurposing approach may assist in identifying novel repurposing events in cancer patients with advanced tumours and no access to standard therapies. Further validation is needed to confirm the utility of a precision oncology approach using drug repurposing.