bluuebunny/crossref_metadata_2025_split huggingface dataset:
A massive community-science dataset reveals convergent evolution of delayed flowering phenology in North American red-flowering plants
Authors: McKenzie Patrick F. , Berardi Andrea E. , Hopkins Robin 
Published: September 2024

SummaryThe radiation of angiosperms is marked by a phenomenal diversity of floral size, shape, color, scent, and reward. Through hundreds of years of documentation and quantification, scientists have sought to make sense of this variation by defining pollination syndromes. These syndromes are the convergent evolution of common suits of floral traits across distantly related species that have evolved by selection to optimize pollination strategies. The availability of community-science datasets provides an opportunity to develop new tools and to examine new traits that may help further characterize broad patterns of flowering plant diversity. Here we test the hypothesis that flowering phenology can also be a pollination syndrome trait. We generate a novel flower color dataset by using GPT-4 with Vision (GPT-4V) to assign flower color to 11,729 North American species. We map these colors to 1,674,908 community-scientist observations of flowering plants to investigate patterns of phenology. We demonstrate constrained flowering time in the eastern United States for plants with red or orange flowers relative to plants with flowers of other colors. Red-and orange-colored flowers are often characteristic of the “hummingbird” pollination syndrome; importantly, the onset of red and orange flowers corresponds to the arrival of migratory hummingbirds. Our results suggest that the hummingbird pollination syndrome can include flowering phenology and reveal an opportunity to expand the suite of traits included in pollination syndromes. Our methods demonstrate an effective pipeline for leveraging enormous amounts of community science data by using artificial intelligence to extract information about patterns of trait variation.
WIMOAD: Weighted Integration of Multi-Omics data for Alzheimer’s Disease (AD) Diagnosis
Authors: Xiao Hanyu , Wang Jieqiong , Wan Shibiao 
Published: September 2024

AbstractAs the most common subtype of dementia, Alzheimer’s disease (AD) is characterized by a progressive decline in cognitive functions, especially in memory, thinking, and reasoning ability. Early diagnosis and interventions enable the implementation of measures to reduce or slow further regression of the disease, preventing individuals from severe brain function decline. The current framework of AD diagnosis depends on A/T/(N) biomarkers detection from cerebrospinal fluid or brain imaging data, which is invasive and expensive during the data acquisition process. Moreover, the pathophysiological changes of AD accumulate in amino acids, metabolism, neuroinflammation, etc., resulting in heterogeneity in newly registered patients. Recently, next generation sequencing (NGS) technologies have found to be a non-invasive, efficient and less-costly alternative on AD screening. However, most of existing studies rely on single omics only. To address these concerns, we introduce WIMOAD, a weighted integration of multi-omics data for AD diagnosis. WIMOAD synergistically leverages specialized classifiers for patients’ paired gene expression and methylation data for multi-stage classification. The resulting scores were then stacked with MLP-based meta-models for performance improvement. The prediction results of two distinct meta-models were integrated with optimized weights for the final decision-making of the model, providing higher performance than using single omics only. Remarkably, WIMOAD achieves significantly higher performance than using single omics alone in the classification tasks. The model’s overall performance also outperformed most existing approaches, highlighting its ability to effectively discern intricate patterns in multi-omics data and their correlations with clinical diagnosis results. In addition, WIMOAD also stands out as a biologically interpretable model by leveraging the SHapley Additive exPlanations (SHAP) to elucidate the contributions of each gene from each omics to the model output. We believe WIMOAD is a very promising tool for accurate AD diagnosis and effective biomarker discovery across different progression stages, which eventually will have consequential impacts on early treatment intervention and personalized therapy design on AD.
CLYBL averts methylmalonyl-CoA mutase inhibition and loss of vitamin B12 by repairing malyl-CoA
Authors: Griffith Corey M. , Conrotte Jean-François , Paydar Parisa , Xie Xinqiang , Heins-Marroquin Ursula , Gavotto Floriane , Jäger Christian , Ellens Kenneth W. , Linster Carole L. 
Published: September 2024

AbstractCitrate lyase beta-like protein (CLYBL) is a ubiquitously expressed mammalian enzyme known for its role in the degradation of itaconate, a bactericidal immunometabolite produced in activated macrophages. The association ofCLYBLloss-of-function with reduced circulating vitamin B12 levels was proposed to result from inhibition of the B12-dependent enzyme methylmalonyl-CoA mutase (MCM) by itaconyl-CoA. The discrepancy between the highly inducible and locally confined production of itaconate and the broad expression profile ofCLYBLacross tissues, suggested a role for this enzyme beyond itaconate catabolism. We discovered that CLYBL additionally functions as a metabolite repair enzyme for malyl-CoA, a side-product of promiscuous TCA cycle enzymes. We found thatCLYBLknockout cells, accumulating malyl-CoA but not itaconyl-CoA, show decreased levels of adenosylcobalamin and that malyl-CoA is a more potent inhibitor of MCM than itaconyl-CoA. Our work thus suggests that malyl-CoA plays a role in the B12 deficiency observed in individuals withCLYBLloss-of-function.Graphical Abstract
Development of nanobodies against human Survivin, applicable to suppress cell proliferation
Authors: Tagawa Ayako , Fuchigami Takeshi , Miyanari Yusuke 
Published: September 2024

AbstractSurvivin, a member of the inhibitor of apoptosis protein (IAP) family, is overexpressed in many cancers, making it a valuable target for therapy and a biomarker for cancer diagnostics. As Survivin contributes to cancer development by inhibiting apoptosis and promoting rapid cell division, inhibiting its activity is a promising strategy to overcome cancer resistance to apoptosis and reduce tumor growth. In this study, we developed nanobodies targeting human Survivin using M13 phage display and deep sequencing to identify high-affinity binders. Seven nanobody clones were selected and evaluated through ELISA, western blotting, and immunostaining. Clones 7 and 15, which specifically bind the alpha-helix region of Survivin, effectively suppressed cell proliferation by disrupting cell cycle regulation, likely by interfering interaction with intracellular binding partners. These findings suggest that Survivin-targeting nanobodies hold potential as therapeutic agents for cancer treatment, offering a novel approach to inhibiting tumor growth through the disruption of Survivin-mediated processes.
Fascicle stretch during partial muscle deactivation does not enhance the human tibialis anterior’s subsequent neuromechanical output
Authors: Raiteri Brent James , De Lorenzo Ricardo , Kraul Malte , Hahn Daniel 
Published: September 2024

ABSTRACTWe were interested in whether stretching the muscle via elastic tissue recoil during partial muscle deactivation could trigger stretch-induced mechanisms that subsequently enhance the muscle’s steady-state neuromechanical output. Two torque-controlled experiments were conducted to test this aim. In Experiment 1, fifteen participants performed fixed-end dorsiflexion contractions to a moderate or high-then-moderate level with torque-drop rates of 0, 10, 20, 40, or 80% MVC·s-1from 60-40% MVC, while net ankle joint torque, tibialis anterior (TA) muscle activity level, and TA ultrasound images were recorded. The same measurements were performed in Experiment 2, which tested twelve different participants who performed fixed-end contractions to three reference levels or to a higher-then-lower level (with torque-drop amplitudes of 85-45, 85-30, and 85-15% MVC at 20% MVC·s-1). Increased fascicle shortening amplitudes (Experiment 1: 1-2 mm,p≤.049; Experiment 2: 5-10 mm,p<.001) to initially higher joint torques and different fascicle stretch rates (0.6 to 4.3 mm·s-1,p≤.041) and amplitudes (4-9 mm;p≤.001) did not significantly affect TA’s subsequent muscle activity level relative to the reference contractions at similar joint torques (0-1% MVC,p≥.659 andp≥.626). However, the torque steadiness relative to the reference conditions was significantly reduced after the 85-15% MVC (p=.036) and 85-30% MVC (p=.036) torque drops. Consequently, the history of force production affected the control of muscle force more than TA’s steady-state neuromuscular output. These findings indicate that assessing fascicle kinematics concurrently with motor unit behavior during fixed-end contractions with large torque drops might provide unique insights into the neuromechanical contributors to impaired torque control.NEW & NOTEWORTHYThe history of force production affected the subsequent control of dorsiflexion torque more than tibialis anterior’s (TA’s) neuromuscular output following larger amounts of fascicle stretch during fixed-end contractions. Larger fascicle stretches also reduced the median frequency of TA’s EMG signal, which tentatively indicates that the voluntary control of muscle force was altered in the steady state. Together, these findings indicate that voluntary force control might be impaired by stretch-induced and/or activity-level-dependent mechanisms during fixed-end contractions.
Assessing coverage of the Monitoring Framework of the Kunming-Montreal Global Biodiversity Framework and opportunities to fill gaps
Authors: Affinito F. , Butchart S. H. M. , Nicholson E. , Hirsch T. , Williams J. M. , Campbell J. , Ferrari M. F. , Gabay M. , Gorini L. , Kalamujic Stroil B. , Kohsaka R. , Painter B. , Pinto J. C. , Scholz A. H. , Straza T. R. A. , Tshidada N. , Vallecillo S. , Widdicombe S. , Gonzalez A. 
Published: September 2024

AbstractThe Kunming-Montreal Global Biodiversity Framework (GBF) is the most ambitious agreement on biodiversity conservation and sustainable use to date. It calls for a whole-of government and whole-of-society approach to halt and reverse biodiversity loss worldwide. The Monitoring Framework of the GBF lays out how Parties to the Convention on Biological Diversity (CBD) are expected to report their progress. A CBD expert group provided guidance on its implementation, including a gap analysis to identify the strengths and limitations of the indicators in the Monitoring Framework. We present the results of the gap analysis, highlight where more work is needed and provide recommendations on implementing and improving monitoring to allow effective and comprehensive tracking of the GBF’s ambition. We find that with the headline and binary indicators, which Parties are required to use, the Monitoring Framework fully covers 19% of the GBF’s ambition and partially covers an additional 40%. Including disaggregations of the headline indicators improves coverage to 22% fully and an additional 41% partially. Adding optional (component and complementary) indicators brings full coverage to 29% with an additional 47% partial coverage. No indicators are available for 12% of the GBF. In practice, the coverage of the Monitoring Framework will depend on which indicators (headline and binary as well as component and complementary) and disaggregations are used by countries. Disaggregations are particularly relevant to monitor the cross-cutting considerations defined under section C. Substantial investment is required to collect the necessary data to compute indicators, infer change, and effectively monitor progress. We highlight important next steps to progressively improve the efficacy of the Monitoring Framework.
3D photogrammetry as a low cost, portable and noninvasive method for acoustic modeling of hearing
Authors: Vesterholm Karsten Krautwald , Häfele Felix T. , Figeac Florence , Jakobsen Lasse 
Published: September 2024

AbstractAnimals with specialized hearing such as bats utilize the directionality of their hearing for complicated tasks such as navigation and foraging. The directionality of hearing can be described through the head related transfer function (HRTF). Current state of the art for obtaining the HRTF involves either direct measurement with a microphone at the eardrum, or a μCT (micro computed tomography) scan to create a 3D model of the head for acoustic modelling. Both methods usually involve dead animals.We developed a 3D photogrammetry approach to create scaled 3D models of bats with sufficient detail to simulate the HRTF using the boundary element method (BEM). We designed a setup of 28 cameras to obtain 3D models and HRTF from live awake bats. We directly compare the mesh models generated by our photogrammetry method and from μCT scans as well as the simulated HRTFs from both with measurements using an in-ear microphone.Geometries of the mesh models match well between photogrammetry and μCT, but with increasing errors where line of sight is compromised for photogrammetry. The resulting HRTFs are in great agreement when comparing μCT and in-ear measurements to photogrammetry (correlation coefficients above 0.6). The 3D model and simulated HRTF of the live and awake bat likewise aligns well to the results from the deceased animals.Photogrammetry is a viable alternative to μCT scans for the generation of surface models of small animals. These models allow numerical modelling of HRTFs at biologically relevant frequencies. Moreover, photogrammetry allows for model generation and subsequent HRTF simulation of live, awake animals, abolishing the need for euthanasia and anesthesia. It paves the way for large scale acquisition of 3D models for various purposes including HRTFs.
Forecasting range shifts of a dioecious plant species under climate change
Authors: Moutouama Jacob K. , Compagnoni Aldo , Miller Tom E.X. 
Published: September 2024

AbstractGlobal warming has triggered an urgent need for predicting the reorganization of Earth’s biodiversity. Currently, the vast majority of models used to forecast population viability and range shifts in response to climate change ignore the complication of sex structure, and thus the potential for females and males to differ in their sensitivity to climate drivers. We developed demographic models of range limitation, parameterized from geographically distributed common garden experiments, with females and males of a dioecious grass species (Poa arachnifera) throughout and beyond its range in the south-central U.S. Female-dominant and two-sex model versions both predict that climate change will alter population viability and will induce a poleward niche shift beyond current northern limits. However, the magnitude of niche shift was underestimated by the female-dominant model, because females have broader temperature tolerance than males and become mate-limited under female-biased sex ratios. Our result illustrate how explicit accounting for both sexes could enhance population viability forecasts and conservation planning for dioecious species in response to climate change.
Biochemical Characterization and Inhibitor Discovery forPfSir2A – New Tricks for An Old Enzyme
Authors: Donu Dickson , Boyle Emily , Curry Alyson , Cen Yana 
Published: September 2024

ABSTRACTThe Sir2 enzyme fromPlasmodium falciparum(PfSir2A) is essential for the antigenic variation of this parasite, and its inhibition is expected to have therapeutic effects for malaria. SelectivePfSir2A inhibitors are not available yet, partially due to the fact that this enzyme demonstrates extremely weakin vitrodeacetylase activity, making the characterization of its inhibitors rather challenging. In the current study, we report the biochemical characterization and inhibitor discovery for this enzyme.PfSir2A exhibits greater enzymatic activity in the presence of DNA for both the peptide and histone protein substrates, suggesting that nucleosomes may be the real substrates of this enzyme. Indeed, it demonstrates robust deacetylase activity against nucleosome substrates, stemming primarily from the tight binding interactions with the nucleosome. In addition to DNA/nucleosome, free fatty acids (FFAs) are also identified as endogenousPfSir2A regulators. Myristic acid, a biologically relevant FFA, shows differential regulation of the two distinct activities ofPfSir2A: activates deacetylation, but inhibits defatty-acylation. The structural basis of this differential regulation was further explored. Moreover, synthetic small molecule inhibitors ofPfSir2A were discovered through the screening of a library of human sirtuin regulators. The mechanism of inhibition of the lead compounds were investigated. Collectively, the mechanistic insights and inhibitors described in this study will facilitate the future development of small moleculePfSir2A inhibitors as antimalarial agents.
Maintenance of synaptic plasticity by negative-feedback of synaptic protein elimination: Dynamic modeling of KIBRA-PKMζ interactions in LTP and memory
Authors: Shouval Harel Z. , Flores-Obando Rafael E. , Sacktor Todd C. 
Published: September 2024

AbstractActivity-dependent modifications of synaptic efficacies are a cellular substrate of learning and memory. Current theories propose that the long-term maintenance of synaptic efficacies and memory is accomplished via a positive-feedback loop at the level of production of a protein species or a protein state. Here we propose a qualitatively different theoretical framework based on negative-feedback at the level of protein elimination. This theory is motivated by recent experimental findings regarding the binding ofPKMζand KIBRA, two synaptic proteins involved in maintenance of memory, and on how this binding affects the proteins’ degradation. We demonstrate this theoretical framework with two different models, a simple abstract model to explore generic features of such a process, and an experimentally motivated phenomenological model. The results of these models are qualitatively consistent with existing data, and generate novel predictions that could be experimentally tested to further validate or reject the negative-feedback theory.
Tunable Elliptical Cylinders for Rotational Mechanical Studies of Single DNA Molecules
Authors: Hong Yifeng , Ye Fan , Gao Xiang , Inman James T. , Wang Michelle D. 
Published: September 2024

AbstractThe angular optical trap (AOT) is a powerful technique for measuring the DNA topology and rotational mechanics of fundamental biological processes. Realizing the full potential of the AOT requires rapid torsional control of these processes. However, existing AOT quartz cylinders are limited in their ability to meet the high rotation rate requirement while minimizing laser-induced photodamage. In this work, we present a novel trapping particle design to meet this challenge by creating small metamaterial elliptical cylinders with tunable trapping force and torque properties. The optical torque of these cylinders arises from their shape anisotropy, with their optical properties tuned via multilayered SiO2and Si3N4deposition. We demonstrate that these cylinders can be rotated at about 3 times the rate of quartz cylinders without slippage while enhancing the torque measurement resolution during DNA torsional elasticity studies. This approach opens new opportunities for previously inaccessible rotational studies of DNA processing.
DefiningTarget Population of Environmentsto Enviromics Studies Using R-based GIS Tools
Authors: Cruz Demila D. M. , Heinemann Alexandre B. , Marcatti Gustavo E. , Resende Rafael T. 
Published: September 2024

AbstractWe propose an R-based function that facilitates the definition of TPE (Target Population of Environments) as GIS polygons for enviromics studies in plant breeding. By adjusting parameters such as pixel size, buffers, and concavity, this function enhances envirotypic-based G×E interaction analysis and provides a flexible tool to optimize environmental and spatial assessments.
Second-Generation Cap Analogue Prodrugs for Targeting Aberrant Eukaryotic Translation Initiation Factor 4E (eIF4E) Activity in Drug-Resistant Melanoma
Authors: Cárdenas Emilio L. , O’Rourke Rachel L. , Menon Arya , Vega-Hernández Gabriela , Meagher Jennifer , Stuckey Jeanne , Garner Amanda L. 
Published: September 2024

ABSTRACTMelanoma is the deadliest form of skin cancer with a 5-year survival rate of less than 20%. While significant strides have been made in the field of kinase-targeted and immune-based therapies for melanoma, the development of resistance to these therapeutic agents has hindered the success of treatment. Drug-resistant melanoma is particularly reliant on enhanced cap-dependent translation to drive the production of oncoproteins that promote growth and survival. The m7GpppX cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) is the rate-limiting factor of cap-dependent translation initiation, and its overexpression in melanoma tumors has been shown to drive resistance to BRAFV600Ekinase-targeted inhibitors. These findings point to eIF4E-targeted therapies as a promising strategy to overcome drug resistance in melanoma. Herein, we build upon our previous work of developing cell-permeable cap analogue inhibitors to design second-generation cap analogues that inhibit eIF4E-mediated cap-dependent translation in drug-resistant melanoma cells.
Temporal Information Encoding in Isolated Cortical Networks
Authors: Ferdous Zubayer Ibne , Berdichevsky Yevgeny 
Published: September 2024

AbstractTime-dependent features are present in many sensory stimuli. In the sensory cortices, timing features of stimuli are represented by spatial as well as temporal code. A potential mechanism by which cortical neuronal networks perform temporal-to-spatial conversion is ‘reservoir computing’. The state of a recurrently-connected network (reservoir) represents not only the current stimulus, or input, but also prior inputs. In this experimental study, we determined whether the state of an isolated cortical network could be used to accurately determine the timing of occurrence of an input pattern – or, in other words, to convert temporal input features into spatial state of the network. We used an experimental system based on patterned optogenetic stimulation of dissociated primary rat cortical cultures, and read out activity via fluorescent calcium indicator. We delivered input sequences of patterns such that a pattern of interest occurred at different times. We developed a readout function for network state based on a support vector machine (SVM) with recursive feature elimination and custom error correcting output code. We found that the state of these experimental networks contained information about inputs for at least 900 msec. Timing of input pattern occurrence was determined with 100 msec precision. Accurate classification required many neurons, suggesting that timing information was encoded via population code. Trajectory of network state was largely determined by spatial features of the stimulus, with temporal features having a more subtle effect. Local reservoir computation may be a plausible mechanism for temporal/spatial code conversion that occurs in sensory cortices.Significance StatementHandling of temporal and spatial stimulus features is fundamental to the ability of sensory cortices to process information. Reservoir computation has been proposed as a mechanism for temporal-to-spatial conversion that occurs in the sensory cortices. Furthermore, reservoirs of biological, living neurons have been proposed as building blocks for machine learning applications such as speech recognition and other time-series processing. In this work, we demonstrated that living neuron reservoirs, composed of recurrently connected cortical neurons, can carry out temporal-spatial conversion with sufficient accuracy and at sufficiently long time scale to be a plausible model for information processing in sensory cortices, and to have potential computational applications.