bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adoption of Modern Beekeeping Technologies and Best Management Practices Among Honey Beekeepers in South West, Nigeria
Authors: Adekola P.J , Aderanti A , Oladoja M. A , Bobadoye Bridget O 
Published: June 2024

ABSTRACTColony collapse disorder (CCD) is an abnormal phenomenon which has been largely undocumented in Nigeria. However, several factors have been attributed to high cases of hive abandonment, amongst which is low adoption of hive management practices. This study was carried out to determine adoption of modern technologies and hive management practices amongst beekeepers within the south-west region of Nigeria to reduce the incidence of CCD. A multistage sampling procedure was used to select a total of 399 beekeepers in beekeeping zones across Ekiti, Oyo and Osun and Ondo States in South-West, Nigeria. Interview schedules were used to collect information on beekeepers to determine the level of adoption of modern beekeeping technologies among honey beekeepers to mitigate against colony collapse and results showed that honey beekeepers perception, benefits derived and constraints to adoption of modern honey beekeeping technologies determined what best management practices to adopt. In light of these findings, it is clear that beekeeping in Southwest Nigeria holds significant promise as a source of income and livelihood improvement. To harness this potential, policymakers, government agencies, and relevant stakeholders must consider tailored strategies to address the unique challenges faced by beekeepers in different states. Encouraging the adoption of modern beekeeping technologies and providing the necessary support systems can contribute to the sustainable growth of the beekeeping industry in the region.In conclusion, there is a need for enhanced education and training initiatives to improve beekeepers’ knowledge of good management practices, which can positively impact beekeeping outcomes. Moreover, addressing the issues related to time constraints and the lack of time for bee farm monitoring is essential to ensure the efficient management of beekeeping activities. The losses and consequent economic damages have encouraged researchers to develop new strategies to control honeybee diseases and pest infestations through the adoption of modern technology.
The comparison of single-cell RNA sequencing platforms based droplets
Authors: Wang Linyan , Zhong Yulong 
Published: June 2024

AbstractSingle-cell sequencing enables to reveal cellular heterogeneity and discover new cellular subpopulations. In terms of the strategy of single-cell sequencing, the main methods are based with combinatorial index, microwell and microfluidic. Due to the simplicity, methods based droplets are widely used for single-cell sequencing for multi-omics. Therefore, in order to facilitate researchers to choose a suitable platform to meet their application scenarios, we compared several commercial platforms: the Chromium X platform of 10x Genomics, the MobiNova-100 platform of MobiDrop, the SeekOne platform of SeekGene, and the C4 platform of BGI. Based the comprehensive assessment of the data analysis, the Chromium X platform shows a excellent performance, closely followed by MobiNova-100 platform.One-Sentence SummaryAs droplet-based single-cell sequencing platforms, Chromium X and MobiNova-100 have comparable data performance.
Methemoglobin aggregation is modulated by the anti-sickling drug voxelotor
Authors: Cove Brandon , Munoz Aldo , Singh Arnav , Jann Gavin , Brandon Kristal , Xing Li , Cocco Melanie J. 
Published: June 2024

ABSTRACTSickle cell disease is caused by a mutation in the beta subunit of hemoglobin (HbSS) that drives Hb fiber formation when the protein is in the deoxygenated (tense, T) state. The drug voxelotor was recently approved to treat sickle cell disease by preventing HbSS fiber formation. Voxelotor acts as an allosteric inhibitor of polymerization by maintaining the HbSS protein in the relaxed (R) conformation, limiting polymerization of T-state fibers. Normal blood cells contain small amounts of natural Hb fibers and a few percent of the Fe3+ferric form, metHb, incapable of binding oxygen. Although the drug Voxelotor is now in use, the effect of the drug on the oxidized metHb state has not been reported. Here we assessed the influence of voxelotor on normal human metHb. We compared the aggregation of metHb at two pH values (5.5 and 7.1). MetHb is known to form organized fiber structures at or below pH 5.5. We find that voxelotor significantly enhances fiber formation of metHb R-state at pH 5.5, consistent with the mode of action for this drug in maintaining the Hb R conformation. The opposite effect is observed at physiological pH values. Voxelotor significantly decreases the rate of metHb aggregate formation at pH 7.1 but did not affect protein stability. Notably, drug binding drives metHb into novel spherical particles with a morphology never seen before for Hb. The formation of these particles should be considered in patients being treated for sickle cell disease with voxelotor.WHY IT MATTERSVoxelotor is an FDA-approved drug for sickle cell anemia, known to prevent hemoglobin fiber formation. Here, we investigate its effect on methemoglobin, the form of hemoglobin in which iron takes on the ferric Fe3+state. Our study examines voxelotor’s impact on methemoglobin aggregation and stability. At pH 7.1, we found voxelotor to have an effect on methemoglobin solubility as evidenced by the formation of novel methemoglobin spherical structures. We observe that voxelotor significantly increases methemoglobin fiber formation at pH 5.5 but, notably, reduces methemoglobin aggregation at physiological pH levels. Minimal impact on methemoglobin thermodynamic stability is noted. These findings suggest voxelotor’s potential therapeutic efficacy for various hemoglobinopathies, including conditions characterized by Heinz body formation.
PharaCon: A new framework for identifying bacteriophages via conditional representation learning
Authors: Bai Zeheng , Zhang Yao-zhong , Pang Yuxuan , Imoto Seiya 
Published: June 2024

AbstractMotivationIdentifying bacteriophages (phages) within metagenomic sequences is essential for understanding microbial community dynamics. Transformer-based foundation models have been successfully employed to address various biological challenges. However, these models are typically pre-trained with self-supervised tasks that do not consider label variance in the pre-training data. This presents a challenge for phage identification as pre-training on mixed bacterial and phage data may lead to information bias due to the imbalance between bacterial and phage samples.ResultsTo overcome this limitation, this study proposed a novel conditional BERT framework that incorporates labels during pre-training. We developed an approach using a conditional BERT model for pre-training labeled data, incorporating label constraints with modified language modeling tasks. This approach allows the model to acquire label-conditional sequence representations. Additionally, we proposed a solution that utilizes conditional BERT in the fine-tuning phase as a classifier. We applied this conditional BERT framework to identify phages using a novel fine-tuning strategy, introducing PharaCon. We evaluated PharaCon against several existing methods on both simulated sequence datasets and real metagenomic contig datasets. The results demonstrate PharaCon's potential as an effective and efficient method for phage identification, highlighting the effectiveness of conditional B ERT as a solution for learning label-specific representations during pre-training on mixed sequence data.AvailabilityThe codes of PharaCon are now available in:https://github.com/Celestial-Bai/PharaCon.Contactyaozhong@ims.u-tokyo.ac.jpandimoto@hgc.jp
Dynamic changes in neuronal and glial GAL4 driver expression duringDrosophilaageing
Authors: Delandre Caroline , McMullen John P. D. , Marshall Owen J. 
Published: June 2024

AbstractUnderstanding how diverse cell types come together to form a functioning brain relies on the ability to specifically target these cells. This is often done using genetic tools such as the GAL4/UAS system inDrosophila melanogaster. Surprisingly, despite its extensive usage during studies of the ageing brain, detailed spatio-temporal characterisation of GAL4 driver lines in adult flies has been lacking. Here we show that three commonly used neuronal drivers (elav[C155]-GAL4,nSyb[R57C10]-GAL4andChAT-GAL4) and the commonly used glial driverrepo-GAL4all show rapid and pronounced decreases in activity over the first 1.5 weeks of adult life, with activity becoming undetectable in some regions after 30 days. In addition to an overall decrease in GAL4 activity over time, we found notable differences in spatial patterns, mostly occurring soon after eclosion. Although all lines showed these changes, thenSyb-GAL4line exhibited the most consistent and stable expression patterns over ageing. Our findings suggest that gene transcription of key loci decreases in the aged brain, a finding broadly similar to previous work in mammalian brains. Our results also raise questions over past work on long-term expression of disease models in the brain, and stress the need to find better genetic tools for ageing studies.
AI-assisted decoding of molecular signatures essential for NON-PHOTOTROPIC HYPOCOTYL3 condensation and function in phototropism
Authors: Manishankar Prabha , Reuter Lea , Rohr Leander , Fernandez Atiara , Yigit Yeliz Idil , Schmidt Tanja , Droste-Borel Irina , Keicher Jutta , Bock Andrea , Oecking Claudia 
Published: June 2024

ABSTRACTThe plasma membrane-associated protein NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) is a key component of plant phototropism. Blue light induces the release of NPH3 into the cytosol, where it dynamically transitions into membrane-less biomolecular condensates. Here, we combine experimental data with the power of AI-based protein structure prediction to uncover a bipartite C-terminal motif that enables self-interaction of NPH3. We further demonstrate its importance for both the association of NPH3 with the plasma membrane and the assembly of condensates in the cytosol, with a different part of the bipartite motif playing the key role in each case. However, the formation of cytosolic condensates additionally requires the co-operative action of an N-terminal NPH3 signature. We propose that NPH3 forms a crosslinked 3D network in the cytosol based on distinct molecular determinants that simultaneously self-associate. NPH3 variants incapable of condensation are non-functional, suggesting a fundamental role of NPH3 phase separation for phototropism. This structural snapshot could have direct implications for future analyses of the plant-specific NPH3/RPT2-Like protein family.
Avoidable false PSMC population size peaks occur across numerous studies
Authors: Hilgers Leon , Liu Shenglin , Jensen Axel , Brown Thomas , Cousins Trevor , Schweiger Regev , Guschanski Katerina , Hiller Michael 
Published: June 2024

SummaryInferring historical population sizes is key to identify drivers of ecological and evolutionary change, and crucial to predict the future of species on our rapidly changing planet. The pairwise sequentially Markovian coalescent (PSMC) method provided a revolutionary framework to reconstruct species’ demographic histories over millions of years based on the genome sequence of a single individual1. Here, we detected and solved a common artifact in PSMC and related methods: recent population peaks followed by population collapses. Combining real and simulated genomes, we show that these peaks do not represent true population dynamics. Instead, ill-set default parameters cause false peaks in our own and published data, which can be avoided by adjusted parameter settings. Furthermore, we show that certain population structure changes can cause similar patterns. Newer methods like Beta-PSMC perform better, but do not always avoid this artifact. Our results suggest testing multiple parameters before interpreting recent population peaks followed by collapses, and call for the development of robust methods.
IspE Kinase as an Anti-infective Target: Role of a Hydrophobic Pocket in Inhibitor Binding
Authors: Hamid Rawia , Walsh Danica J. , Diamanti Eleonora , Aguilar Diana , Lacour Antoine , Hamed Mostafa M. , Hirsch Anna K. H. 
Published: June 2024

AbstractEnzymes of the methylerythritol phosphate (MEP) pathway are potential targets for antimicrobial drug discovery. Here we focus on 4-diphosphocytidyl-2-C-methyl-D-erythritol (IspE) kinase from the MEP pathway. We use biochemical and structural biology methods to investigate homologs from the pathogenic microorganisms;Escherichia coli, Klebsiella pneumoniae, andAcinetobacter baumannii. We determined the X-ray structures of IspE-inhibitor complexes and studied selected inhibitors’ binding modes targeting the substrate pocket. The experimental results indicate the need for distinct inhibitor strategies due to structural differences among IspE homologs, particularly for A. baumannii IspE, which displays unique inhibitory profile due to a tighter hydrophobic subpocket in the substrate binding site. This study enhances our understanding of the MEP enzymes and sets the stage for structure-based drug design of selective inhibitors to combat pathogenic microorganisms.
Path-based reasoning for biomedical knowledge graphs with BioPathNet
Authors: Hu Yue , Oleshko Svitlana , Firmani Samuele , Zhu Zhaocheng , Cheng Hui , Ulmer Maria , Arnold Matthias , Colomé-Tatché Maria , Tang Jian , Xhonneux Sophie , Marsico Annalisa 
Published: June 2024

AbstractUnderstanding complex interactions in biomedical networks is crucial for advancements in biomedicine, but traditional link prediction (LP) methods are limited in capturing this complexity. Representation-based learning techniques improve prediction accuracy by mapping nodes to low-dimensional embeddings, yet they often struggle with interpretability and scalability. We present BioPathNet, a novel graph neural network framework based on the Neural Bellman-Ford Network (NBFNet), addressing these limitations through path-based reasoning for LP in biomedical knowledge graphs. Unlike node-embedding frameworks, BioPathNet learns representations between node pairs by considering all relations along paths, enhancing prediction accuracy and interpretability. This allows visualization of influential paths and facilitates biological validation. BioPathNet leverages a background regulatory graph (BRG) for enhanced message passing and uses stringent negative sampling to improve precision. In evaluations across various LP tasks, such as gene function annotation, drug-disease indication, synthetic lethality, and lncRNA-mRNA interaction prediction, BioPathNet consistently outperformed shallow node embedding methods, relational graph neural networks and task-specific state-of-the-art methods, demonstrating robust performance and versatility. Our study predicts novel drug indications for diseases like acute lymphoblastic leukemia (ALL) and Alzheimer’s, validated by medical experts and clinical trials. We also identified new synthetic lethality gene pairs and regulatory interactions involving lncRNAs and target genes, confirmed through literature reviews. BioPathNet’s interpretability will enable researchers to trace prediction paths and gain molecular insights, making it a valuable tool for drug discovery, personalized medicine and biology in general.
Biochemical and structural insights into the auto-inhibited state of Mical1 and its activation by Rab8
Authors: Rai Amrita , Janning Petra , Vetter Ingrid R. , Goody Roger S. 
Published: June 2024

AbstractMical1 regulates F-actin dynamics through the reversible oxidation of actin, a process controlled by its interactions with various proteins. Upon binding to Rab8 family members, Mical1 links endosomes to the cytoskeleton, promoting F-actin disassembly. In the absence of Rab, Mical1 exists in an auto-inhibited state, but its biochemical characterization remains incomplete. Our study reveals that the N-terminal MO-CH-LIM domains of Mical1 form an intramolecular complex with its C-terminal bMERB domain. Mutational analysis, guided by the AlphaFold2 model, identifies critical residues at the binding interface. Additionally, we demonstrate that full-length Mical1 binds to Rab8 in a 1:2 stoichiometry, thereby releasing auto-inhibition. Through structure-based mutational studies, we uncover allostery between the N and C-terminal Rab binding sites. Notably, Rab binding at the high-affinity C-terminal site precedes binding at the N-terminal site, suggesting a sequential binding mode. These findings elucidate how Rab8 binding releases the MO-CH-LIM domains from the Mical1 bMERB domain, facilitating interactions with other proteins and the actin cytoskeleton, thereby modulating actin dynamics.
A bottom-up approach identifies the antipsychotic and antineoplastic trifluoperazine and the ribose derivative deoxytubercidin as novel microglial phagocytosis inhibitors
Authors: Rodriguez-Iglesias Noelia , Paris Iñaki , Valero Jorge , Cañas-Zabala Lorena , Carretero Alejandro , Hatje Klas , Zhang Jitao David , Patsch Christoph , Britschgi Markus , Gutbier Simon , Sierra Amanda 
Published: June 2024

ABSTRACTPhagocytosis is an indispensable function of microglia, the brain professional phagocytes. Microglia are particularly efficient phagocytosing cells that undergo programmed cell death (apoptosis) in physiological conditions. However, mounting evidence suggests microglial phagocytosis dysfunction in multiple brain disorders. These observations prompted us to search for phagocytosis modulators (enhancers or inhibitors) with therapeutic potential. We used a bottom-up strategy that consisted on the identification of phagocytosis modulators using phenotypic high throughput screenings (HTSs) in cell culture and validation in organotypic cultures andin vivo. We performed two complementary HTS campagnes: at Achucarro, we used primary cultures of mouse microglia and compounds of the Prestwick Chemical Library; at Roche, we used human iPSC derived macrophage-like cells and a proprietary chemo-genomic library with 2,200 compounds with known mechanism-of-action. Next, we validated the more robust compounds using hippocampal organotypic cultures and identified two hits: trifluoperazine, a dopaminergic and adrenergic antagonist used as an antipsychotic and antineoplastic; and deoxytubercidin, a ribose derivative. Finally, we tested whether these compounds were able to modulate phagocytosis of apoptotic newborn cells in the adult hippocampal neurogenic nichein vivoby administering them into the mouse hippocampus using osmotic minipumps. We confirmed that both trifluoperazine and deoxytubercidin have anti-phagocytic activityin vivo, and validated our bottom-up strategy to identify novel phagocytosis modulators. These results show that chemical libraries with anotated mechanism of action are an starting point for the pharmacological modulation of microglia in drug discovery projects aiming at the therapeutic manipulation of phagocytosis in brain diseases.GRAPHICAL ABSTRACT
Self-organized spatial targeting of contractile actomyosin rings for synthetic cell division
Authors: Reverte-López María , Kanwa Nishu , Qutbuddin Yusuf , Jasnin Marion , Schwille Petra 
Published: June 2024

AbstractOne of the challenges of bottom-up synthetic biology is the engineering of a minimal module for self-division of synthetic cells. To produce the contractile forces required for the controlled excision of cell-like compartments such as giant unilamellar vesicles (GUVs), reconstituted cytokinetic rings made of actin are considered to be among the most promising structures of a potential synthetic division machinery. Although the targeting of actin rings to GUV membranes and their myosin-induced constriction have been previously demonstrated, large-scale vesicle deformation has been precluded due to the lacking spatial control of these contractile structures. Here, we show the combinedin vitroreconstitution of actomyosin rings and the bacterial MinDE protein system, effective in targetingE.coliZ-rings to mid-cell, within GUVs. Incorporating this spatial positioning tool, which induces active transport of any diffusible molecule on membranes, yields self-organized assembly of actomyosin rings at the equatorial plane of vesicles. Remarkably, the synergistic effect of Min oscillations and the contractile nature of actomyosin bundles induces mid-vesicle membrane deformation and striking bleb-like protrusions, leading to shape remodeling and symmetry breaking. Our system showcases how functional machineries from various organisms may be synergistically combinedin vitro, leading to the emergence of new functionality towards a synthetic division system.
Dizocilpine derivatives with neuroprotective effect lacking the psychomimetic side effects
Authors: Konecny Jan , Misiachna Anna , Chvojkova Marketa , Kleteckova Lenka , Kolcheva Marharyta , Novak Martin , Prchal Lukas , Ladislav Marek , Hemelikova Katarina , Netolicky Jakub , Hrabinova Martina , Kobrlova Tereza , Karasova Jana Zdarova , Pejchal Jaroslav , Jendelova Pavla , Pang Yuan-Ping , Vales Karel , Korabecny Jan , Soukup Ondrej , Horak Martin 
Published: June 2024

AbstractWe aimed to prepare novel dibenzosuberane derivatives that act on N-methyl-D-aspartate (NMDA) receptors with potential neuroprotective effects. Our approach involved modifying the tropane moiety of MK-801, a potent open-channel blocker known for its psychomimetic side effects, by introducing a seven-membered ring with substituted base moieties specifically to alleviate these undesirable effects. Ourin silicoanalyses showed that these derivatives should have high gastrointestinal absorption and cross the blood-brain barrier (BBB). Our pharmacokinetic studies in rats supported this conclusion and confirmed the ability of leading compounds3land6fto penetrate the BBB. Electrophysiological experiments showed that all compounds exhibited different inhibitory activity towards the two major NMDA receptor subtypes, GluN1/GluN2A and GluN1/GluN2B. Of the selected compounds intentionally differing in the inhibitory efficacy,6fshowed high relative inhibition (∼90% for GluN1/GluN2A), while3lshowed moderate inhibition (∼50%). Anin vivotoxicity study determined that compounds3land6fwere safe at 10 mg/kg doses with no adverse effects. Behavioral studies demonstrated that these compounds did not induce hyperlocomotion or impair prepulse inhibition of startle response in rats. Neuroprotective assays using a model of NMDA-induced hippocampal neurodegeneration showed that compound3lat a concentration of 30 μM significantly reduced hippocampal damage in rats. These results suggest that these novel dibenzosuberane derivatives are promising candidates for developing NMDA receptor-targeted therapies with minimal psychotomimetic side effects.