bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering Microglial Cells to Promote Spinal Cord Injury Recovery
Authors: Zhou Qingsheng , Liu Jianchao , Fang Qiongxuan , Zhang Chunming , Liu Wei , Sun Yifeng 
Published: July 2024

AbstractSpinal cord injury (SCI) can result in irreversible damage, leading to lifelong paralysis for affected individuals. Microglia’s dual impact on neuronal regeneration after SCI, driven by their distinct roles at different stages, merits further study. We conducted a bioinformatic analysis of single-cell transcriptomes (scRNA), spatial transcriptomic (ST) data, and bulk RNA-seq data from Gene Expression Omnibus (GEO) datasets. The data were processed using R packages such as “Seurat”, “DESeq2”,“limma” and “GSVA.” Additionally, we utilized Gene Set Enrichment Analysis (GSEA) and the Enrichr web servers. Analysis of single-cell data and spatial transcriptomics has revealed notable changes in the microglial cell landscape in SCI. These changes encompass the inhibition of innate microglial cells, while reactive microglial cells exhibit pronounced reactive hyperplasia. Moreover, the TGFβ signaling pathway plays a crucial role in regulating the migration of innate microglial cells to enhance SCI recovery. However, reactive microglial cells exhibiting high Trem2 expression contribute to the neuroinflammatory response and can effectively modulate neural cell death in SCI. In particular, inhibiting Trem2 in reactive microglial cells not only reduces inflammation but also mitigates spinal cord injury, and enhancing the TGFβ signaling pathway. What’s more, the use of iPSC-derived microglial cells, which have demonstrated their capacity to augment the potential for replacing the functions of naive microglial cells, iPSC-derived microglia have the potential to replace the functions of naive microglial cells, holds significant promise in addressing SCI. Therefore, we posit that the engineering of microglial cells to promote the SCI recovery. The approach ofinhibiting Trem2-mediated neuroinflammatory responses and transplanting iPSC-derived microglia with long-term TGFβ stimulation may offer potential improvements in SCI recovery.
PyINETA: Open-source platform for INADEQUATE-JRES integration in NMR metabolomics
Authors: Taujale Rahil , Uchimiya Mario , Clendinen Chaevien S. , Borges Ricardo M. , Turck Christoph W. , Edison Arthur S. 
Published: July 2024

AbstractAnnotating compounds with high confidence is a critical element in metabolomics.13C-detection NMR experiment INADEQUATE (incredible natural abundance double-quantum transfer experiment) stands out as a powerful tool for structural elucidation, whereas this valuable experiment is not often included in metabolomics studies. This is partly due to the lack of community platform that provides structural information based INADEQUATE. Also, it is often the case that a single study uses various NMR experiments synergistically to improve the quality of information or balance total NMR experiment time, but there is no public platform that can integrate the outputs of INADEQUATE and other NMR experiments either. Here, we introduce PyINETA, Python-based INADEQUATE network analysis. PyINETA is an open-source platform that provides structural information of molecules using INADEQUATE, conducts database search, and integrates information of INADEQUATE and a complementary NMR experiment13CJ-resolved experiment (13C-JRES). Those steps are carried out automatically, and PyINETA keeps track of all the pipeline parameters and outputs, ensuring the transparency of annotation in metabolomics. Our evaluation of PyINETA using a model mouse study showed that our pipeline successfully integrated INADEQUATE and13C-JRES. The results showed that13C-labeled amino acids that were fed to mice were transferred to different tissues, and, also, they were transformed to other metabolites. The distribution of those compounds was tissue-specific, showing enrichment of particular metabolites in liver, spleen, pancreas, muscle, or lung. The value of PyINETA was not limited to those known compounds; PyINETA also provided fragment information for unknown compounds. PyINETA is available on NMRbox.
Neuron synchronization analyzed through spatial-temporal attention
Authors: Yang Haoming , Pramod KC , Chen Panyu , Lei Hong , Sponberg Simon , Tarokh Vahid , Riffell Jeffrey A. 
Published: July 2024

AbstractAcross diverse organisms, the temporal dynamics of spiking responses between neurons, the neural synchrony, is crucial for encoding different stimuli. Neural synchrony is especially important in the insect antennal (olfactory) lobe (AL). Previous studies on synchronization, however, rely on pair-wise synchronization metrics including the cross-correlogram and cos-similarity between kernelized spikes train. These pair-wise analyses overlook an important aspect of synchronization which is the interaction at the population neuron level. There are also limited modeling techniques that incorporate the synchronization between neurons in modeling population spike trains. Inspired by recent advancements in machine learning, we leverage a modern attention mechanism to learn a generative normalizing flow that captures neuron population synchronization. Our method not only reveals the spiking mechanism of neurons in the AL region but also produces semi-interpretable attention weights that characterize neuron interactions over time. These automatically learned attention weights allow us to elucidate the known principles of neuron synchronization and further shed light on the functional roles of different cell types (the local interneurons (LNs), and projection neurons (PNs)) in the dynamic neural network in the AL. By varying the balance of excitation and inhibition in this neural circuit, our method further uncovers the pattern between the strength of synchronization and the ratio of an odorant in the mixture.Author SummaryThe olfactory system can accurately compute the mixture of volatile compounds emitted from distant sources, enabling the foraging species to exhibit fast and effective decisions. However, altering ratios of one of the compounds in the mixture could be perceived as a different odor. Leveraging the current understanding of neural synchronization on sensory neural regions of insects, we construct a spatial-temporal attention normalizing flow, which partially replicates the AL region’s functionality by learning the spiking mechanics of neurons. Beyond providing insights of the spiking mechanism of neurons in the AL region, our method also produces semi-interpretable attention weights that characterize neuron interaction over time. These automatically learned attention weights allow us to dissect out the principles of neuron synchronization and interaction mechanisms between projection neurons (PNs) and local neurons (LNs). Utilizing our accurate model of these AL functionality, we show evidence that the behavioral relevant compounds are closely clustered together while varying the intensities of one of the behavioral compounds in the mixture could attenuate the synchronization
Ventral Morphology and Ecological Implications ofCindarella eucalla(Artiopoda, Xandarellida) from Chengjiang Biota, China
Authors: Zhang Maoyin , Liu Yu , Mai Huijuan , Schmidt Michel , Hou Xianguang 
Published: July 2024

AbstractArtiopoda, an early arthropod group, displays post-antennal appendages resembling trilobite limbs, but relationships with other ealy arthropods remain enigmatic. Limited studies and morphological details hinder the understanding of internal relationships within Artiopoda. Recently, exceptionally well preserved arthropod fossils from the Chengjiang Biota were studied using X-ray computed tomography, revealing detailed morphologies. In this study,Cindarella eucalla, a xandarellid from the Chengjiang Biota, was re-investigated using X-ray computed tomography and fluorescent microscopy to reconstruct its morphology and understand its phylogeny and ecology. This study successfully reconstructed a three-dimensional model ofCindarella eucalla, revealing features, such as spindle-shaped trunk tergites with the anterior six covered by the head shield and axial spines extending from the last four, natant hypostome, four post-antennal cephalic appendage pairs, dorsoventral mismatch existed between trunk tergites and limb pairs. This research suggests thatCindarella eucallacould escape in a very short time when it encounters an enemy, and it probably lived in muddy environments with ample light. Phylogenetic analysis indicates that Xandarellids may have close relationship with concililiterga or a clade composed of Nektaspida + (Conciliterga + (Phytophilaspis pergamena+ Trilobita)).
EGFR meets hATG8s – Biophysical and structural insights supporting a unique role of GABARAP during receptor trafficking
Authors: Üffing Alina , Weiergräber Oliver H. , Schwarten Melanie , Hoffmann Silke , Willbold Dieter 
Published: July 2024

AbstractThe human ATG8 family member GABARAP is involved in numerous autophagy-related and - unrelated processes. We recently observed that specifically the deficiency of GABARAP enhances EGFR degradation upon ligand stimulation. Here, we report on two putative LC3-interacting regions (LIRs) within the EGFR, the first of which (LIR1) is selected as GABARAP binding sitein-silico. Indeed,in-vitrointeraction studies reveal preferential binding of LIR1 to GABARAP and GABARAPL1. Our X-ray data demonstrate interaction of core LIR1 residues FLPV with both hydrophobic pockets of GABARAP suggesting a canonical binding. Although LIR1 occupies the LIR docking site, GABARAP Y49 and L50 appear dispensable this case. Our data support the hypothesis that GABARAP affects the fate of EGFR at least in part through direct binding.
Detecting latent gene-environment interaction when analyzing binary traits
Authors: Zhang Ziang , Lawless Jerald F. , Paterson Andrew D. , Sun Lei 
Published: July 2024

AbstractIn genome-wide association studies (GWAS), it is desirable to test for interactions (GxE) between single-nucleotide polymorphisms (SNPs,G’s) and environmental variables (E’s). However, directly accounting for interaction is often infeasible, becauseEis latent. For quantitative traits (Y) that are approximately normally distributed, it has been shown that indirect testing onGxEcan be done by testing for heteroskedasticity ofYbetween genotypes. However, when traits are binary, the existing methodology based on testing the heteroskedasticity of the trait across genotypes cannot be generalized. In this paper, we propose an approach to indirectly testGxEfor binary traits based on the non-additive effectG, and subsequently propose a joint test that accounts for the main and interaction effects of each SNP during GWAS. We illustrate the statistical features including type-I-error control and power of the proposed method through extensive numerical studies. Applying our method to the UK Biobank dataset, we showcase the practical utility of the proposed method, revealing SNPs and genes with strong potential for latent interaction effects.
OpenTn5: Open-Source Resource for Robust and Scalable Tn5 Transposase Purification and Characterization
Authors: Soroczynski Jan , Anderson Lauren J. , Yeung Joanna L. , Rendleman Justin M. , Oren Deena A. , Konishi Hide A. , Risca Viviana I. 
Published: July 2024

AbstractTagmentation combines DNA fragmentation and sequencing adapter addition by leveraging the transposition activity of the bacterial cut-and-paste Tn5 transposase, to enable efficient sequencing library preparation. Here we present an open-source protocol for the generation of multi-purpose hyperactive Tn5 transposase, including its benchmarking in CUT&Tag, bulk and single-cell ATAC-seq. The OpenTn5 protocol yields multi-milligram quantities of pG-Tn5E54K, L372Pprotein per liter ofE. coliculture, sufficient for thousands of tagmentation reactions and the enzyme retains activity in storage for more than a year.
The penetration ring is a novel infection structure formed by the penetration peg for invading plant cell membrane in rice blast fungus
Authors: Fang Wenqin , Zai Xiaoyu , Chen Jia , Abubakar Yakubu Saddeeq , Wu Qiuqiu , Fang Zhenyu , Huang Xiuwei , Gan Xiang , Ebbole Daniel J. , Wang Zonghua , Zheng Wenhui 
Published: July 2024

AbstractMany fungal pathogens develop specialized infection structures such as appressoria to penetrate plant cells. However, it is not clear whether special structures are formed after cell wall penetration before invading host cytoplasm membrane in hemibiotrophic pathogens. Here, we showed that a penetration ring consisting of Ppe1 secreted proteins is formed after appressorium-mediated cell wall penetration and remained at the base of penetration site after invading plant cytoplasm membrane in the rice blast fungusMagnaporthe oryzae. The same persistent Ppe1 ring is formed after the penetration of neighboring cells by transpressoria.PPE1is specifically expressed during plant infection and the Δppe1mutant is defective in penetration and invasive growth. Blockage of penetration peg formation impedes the development of the Ppe1 ring. Close examinations showed that the penetration ring is formed at the collar of penetration pegs between plant cell wall and cytoplasm membrane and it is persistent as a fixed ring even after invasive hyphae invaded neighboring cells. Furthermore, Ppe1 is a member of an expanded family of secreted proteins that are unique to fungal pathogens using extreme appressorium turgor for plant penetration. Other members of the Ppe1 family also localize to the penetration ring for anchoring on cytoplasm membrane during plant infection. Taken together, a penetration ring consisting of a family of secreted proteins is formed between plant cell wall and cytoplasm membrane, which may function as a novel physical structure at the interface between the tip of penetration pegs and plant cytoplasm membrane before the differentiation of invasive hyphae.Significance StatementLike many other plant pathogens, the rice blast fungus forms melanized appressoria (specialized infection structures) to penetrate plant cells. In this study, we showed that a penetration ring is formed by penetration pegs after appressorium- or transpressorium-mediated penetration of plant cell wall. This ring of secreted proteins is persistent at the point of penetration pegs invading plant cytoplasm membrane to form invasive hyphae. Therefore, after the penetration of plant cell wall, the rice blast fungus forms a penetration ring that consists of a family of secreted proteins unique to pathogens using extreme appressorium turgor for penetration and may function as a physical structure for anchoring onto plant cytoplasm membrane and developing invasive hyphae in penetrated cells.
Post-weaning social isolation alters sociability in a sex-specific manner
Authors: Myers Teneisha , Birmingham Elizabeth A. , Rhoads Brigham T. , McGrath Anna G. , Miles Nylah A. , Schuldt Carmen B. , Briand Lisa A. 
Published: July 2024

AbstractAdolescence is a critical period for brain development in humans and stress exposure during this time can have lasting effects on behavior and brain development. Social isolation and loneliness are particularly salient stressors that lead to detrimental mental health outcomes particularly in females, although most of the preclinical work on social isolation has been done in male animals. Our lab has developed a model of post-weaning adolescent social isolation that leads to increased drug reward sensitivity and altered neuronal structure in limbic brain regions. The current study utilized this model to determine the impact of adolescent social isolation on a three-chamber social interaction task both during adolescence and adulthood. We found that while post-weaning isolation does not alter social interaction during adolescence (PND45), it has sex-specific effects on social interaction in adulthood (PND60), potentiating social interaction in male mice and decreasing it in female mice. As early life stress can activate microglia leading to alterations in neuronal pruning, we next examined the impact of inhibiting microglial activation with daily minocycline administration during the first three weeks of social isolation on these changes in social interaction. During adolescence, minocycline dampened social interaction in male mice, while having no effect in females. In contrast, during adulthood, minocycline did not alter the impact of adolescent social isolation in males, with socially isolated males exhibiting higher levels of social interaction compared to their group housed counterparts. In females, adolescent minocycline treatment reversed the effect of social isolation leading to increased social interaction in the social isolation group, mimicking what is seen in naïve males. Taken together, adolescent social isolation leads to sex-specific effects on social interaction in adulthood and adolescent minocycline treatment alters the effects of social isolation in females, but not males.
Pymportx: Facilitating Next-Generation Transcriptomics Analysis in Python
Authors: Pena González Paula , Lozano-Paredes Dafne , Rojo-Álvarez José Luis , Bote-Curiel Luis , Sánchez-Arévalo Lobo Víctor Javier 
Published: July 2024

AbstractThe efficient importation of quantified gene expression data is pivotal in transcriptomics. Historically, the R package Tximport addressed this need by enabling seamless data integration from various quantification tools. However, the Python community lacked a corresponding tool, restricting cross-platform bioinformatics interoperability. We introduce Pymportx, a Python adaptation of Tximport, which replicates and extends the original package’s functionalities. Pymportx maintains the integrity and accuracy of gene expression data while improving processing speed and integration within the Python ecosystem. It supports new data formats and includes tools for enhanced data exploration and analysis. Available under the MIT license, Pymportx integrates smoothly with Python’s bioinformatics tools, facilitating a unified and efficient workflow across the R and Python ecosystems. This advancement not only broadens access to Python’s extensive toolset but also fosters interdisciplinary collaboration and the development of cutting-edge bioinformatics analyses.Availability and ImplementationPymportx is released as an open-source software under the MIT license. The source code is available on GitHub athttps://github.com/victorsanchezarevalo/Pymportx.
Influenza-induced alveolar macrophages protect against death by malaria-associated acute lung injury
Authors: Reed Jenna S. , Nayan Ritika , Deckers Margot , Evavold Brian D. , Lamb Tracey J. 
Published: July 2024

AbstractLower respiratory tract infections are common in malaria-endemic areas, and there is some evidence that co-infections between various bacteria/viruses andPlasmodiummay affect disease prognosis. In this study, we report the novel finding that co-infection with influenza/A/X31 protects mice from death byPlasmodium bergheiNK65-Edinburgh, a model of severe malarial pulmonary leak which underpins malaria-associated acute lung injury (MA-ALI) and malaria-associated acute respiratory distress (MA-ARDS). Co-infected mice exhibit equivalent parasitemia as mice with malaria only, suggesting that the survival phenotype is due to differences in immune kinetics. We demonstrated that the pulmonary leak typical ofPbE is attenuated in co-infected mice without alteration in CD8 T cell activation and recruitment to the lung. Upon further examination of the immune response to influenza/A/X31 we identified a population of arginase 1-expressing alveolar macrophages that traffic to the lungs early during infection. In vitro these macrophages inhibit CD8 T cell activation and proliferation better than non-arginase expressing cells. Removal of arginase-1 expressing alveolar macrophagesin vivovia administration of the antimetabolite gemcitabine removed the protective effects of influenza/A/X31co-infection on MA-ALI. This study opens a route to better understanding of how to modulate the immunopathology observed in pulmonary leak associated with severe malaria, which must be achieved to rationally design therapeutic interventions for MA-ARDS / MA-ALI.
Ideal efficacy photoswitches for TRPC4/5 channels harness high potency for spatiotemporally-resolved control of TRPC function in live tissues
Authors: Müller Markus , Niemeyer Konstantin , Ojha Navin K. , Porav Sebastian A. , Vinayagam Deivanayagabarathy , Urban Nicole , Büchau Fanny , Oleinikov Katharina , Makke Mazen , Bauer Claudia C. , Johnson Aidan V. , Muench Stephen P. , Zufall Frank , Bruns Dieter , Schwarz Yvonne , Raunser Stefan , Leinders-Zufall Trese , Bon Robin S. , Schaefer Michael , Thorn-Seshold Oliver 
Published: July 2024

ABSTRACTDirectly probing the endogenous biological roles of target proteins with high spatial and temporal resolution, as non-invasively and reproducibly as possible, is a shared conceptual goal for research across many fields, as well as for targeted therapies. Here we describe the rational conceptual design and test-case practical implementation of a photopharmacological paradigm to empower high-performance photomodulation studiesin vivo. TRPC4/5 ion channels are involved in many spatiotemporally resolved circuits, from pain and anxiety, to reproductive signaling, digestion, and obesity. To unpick their biology requires spatiotemporally precise tools, which were lacking. We developed “ideal efficacy photoswitch” ligands to control their diverse functionsin situ. TheseE⇆Z-photoswitchable ligands bias TRPC[4]/5 channel activity with exquisite photocontrol, from strong agonism under 360 nm, to low agonism at 385 nm, to strong antagonism at 410-460 nm. Cryo-EM structures of both TRPC4 and TRPC5 with bothZ-agonists andE-antagonists support the rationale for efficacy switching through competitiveE/Zisomer binding. Crucially, since theE/Zratio is exclusively determined by the light wavelength applied,their channel photocontrol is exclusively wavelength-dependent, yet drug-concentration-independent: so is reproducible from cell culture to >millimetre-depth tissues. Indeed, we were able to photocontrol both direct and downstream TRPC4/5 biology in cell lines or primary cells in culture, from calcium flux, to primary neuron excitability and adrenaline release; and even in tissues, photoswitching small intestine motility and peristalsis. The TRPC4/5 ligands we develop will thus unlock a range of high-precision investigations in TRP biology. More broadly, we propose that the success of this efficacy photoswitch program, from concept to tissue level translation, is mainly a consequence of how biology has evolved proteins for efficacy control. We therefore foresee that a variety of functionally responsive protein targets, not only sensory and signaling ion channels and receptors, will be amenable to similarly high-performance photocontrol evenin vivo, if a new generation of reagent development adopts this paradigm ofideal efficacy photoswitching.Table of Contents Graphic
Fundamental frequency predominantly drives talker differences in auditory brainstem responses to continuous speech
Authors: Polonenko Melissa J. , Maddox Ross K. 
Published: July 2024

AbstractDeriving human neural responses to natural speech is now possible, but the responses to male- and female-uttered speech have been shown to differ. These talker differences may complicate interpretations or restrict experimental designs geared toward more realistic communication scenarios. This study found that when a male and female talker had the same fundamental frequency, auditory brainstem responses (ABRs) were very similar. Those responses became smaller and later with increasing fundamental frequency, as did click ABRs with increasing stimulus rates. Modeled responses suggested that the speech and click ABR differences were reasonably predicted by peripheral and brainstem processing of stimulus acoustics.