bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selectivity and evolution of Aqp10 in solute permeability influenced by pore molecular weight
Authors: Nagashima Ayumi , Ushio Kazutaka , Nishihara Hidenori , Akimoto Jin , Kato Akira , Furuta Tadaomi 
Published: March 2024

AbstractAqp10 is an aquaglyceroporin that transports not only water but also uncharged low-molecular-weight compounds. We previously demonstrated the evolution of solute permeability in Aqp10 paralogs and showed that the urea and boric acid permeabilities of Aqp10.2 were much weaker than those of Aqp10.1 and plesiomorphic Aqp10s. However, the molecular mechanism responsible for the weak permeability of Aqp10.2 to urea and boric acid remains unclear. Herein, we present a novel hypothesis that explains the solute selectivity of Aqp10. We deduced the ancestral sequences of Aqp10.1 and Aqp10.2 paralogs via molecular phylogenetic analysis. Constructed structural models of these sequences revealed that both the well known amino acid site at position 3 and the sum of molecular weights of the four amino acid sites in the ar/R region were important for the formation of the Aqp10 selectivity filter. Site-directed mutagenesis revealed that a decrease in the sum of the molecular weights of the four amino acid sites enhanced the Aqp10 permeability to urea and boric acid. Based on this, we proposed a model in which the presence of two or more bulky amino acids in the ar/R region, which increases the sum of the molecular weights of amino acids in the ar/R region, was essential for the formation of a filter that limited urea and boric acid transport. Our results outline the molecular mechanism by which Aqp10.2 acquired a selectivity filter during evolution and provide structural insights into the narrowly tuned filter responsible for the solute selectivity of aquaglyceroporins.Significance StatementIn aquaglyceroporins, particularly Aqp10s, the urea and boric acid permeabilities of Aqp10.2 paralogs are much weaker than those of plesiomorphic Aqp10s. Here, we deduced the ancestral sequences of Aqp10.1 and Aqp10.2 via molecular phylogenetic analysis. Structural models of these sequences revealed that the sum of the four amino acid site molecular weights in the ar/R region, if more than one is bulky, contributed to the selectivity filter formation in the pore region. Using site-directed mutagenesis, reduction in the molecular weight of one bulky amino acid residue in the ar/R region restricted urea and boric acid permeability. Therefore, Aqp10.2 acquired a selectivity filter during evolution, and structural differences in this selectivity filter are responsible for the variable solute permeability of aquaglyceroporins.
Growth parameters of the clupeidsLimnothrissa miodonandStolothrissa tanganicaein northern Lake Tanganyika (Bujumbura sub-basin)
Authors: N’sibula Mulimbwa T. , Gordó-Vilaseca Cesc , Milec Leona J. M. , Patel Deepti M. , Alidor Kankonda Busanga , Micha Jean-Claude , Sarvala Jouko , Raeymaekers Joost A. M. 
Published: March 2024

SUMMARYThe analysis of growth parameters in fish stocks, such as the asymptotic length (L∞) and the curvature parameter (K), is crucial for the estimation of production rates and total mortality rates in fisheries management. Here, we estimated the growth parameters of the clupeidsLimnothrissa miodonandStolothrissa tanganicaein the northern part of Lake Tanganyika (Bujumbura sub-basin). Both species are important targets of pelagic fisheries, but the available estimates are based on scarce size frequency data, and rarely on size as a function of age data. We provide new estimates of L∞and K based on size as a function of age data, with age being inferred from otolith weights. Furthermore, we reanalyze several existing length frequency datasets using advanced statistical procedures to test if growth parameters estimated by length frequency analysis are consistent with those obtained from size as a function of age. We found that length frequency analysis consistently underestimates L∞and overestimates K as compared to length-at-age data. We recommend that length-at-age data are collected at a much broader spatial and temporal scale than currently available to advance our understanding of the growth dynamics of these two sardine species. This will improve the assessment of stock productivity of Lake Tanganyika’s pelagic fisheries and the conservation of these economically important fish species.
Biomimetic fractal topography enhances podocyte maturation in vitro
Authors: Liu Chuan , Aggarwal Praful , Wagner Karl T. , Landau Shira S. , Cui Teng , Song Xin , Shamaei Laleh , Rafatian Naimeh , Zhao Yimu , Rodriguez-Ramirez Sonia , Morton Keith , Virlee Elizabeth , Li Chen Yu , Bannerman Dawn , Pascual-Gil Simon , Okhovatian Sargol , Radisic Anastasia , Clotet-Freixas Sergi , Veres Teodor , Sadrzadeh Mohtada , Filleter Tobin , Broeckel Ulrich , Konvalinka Ana , Radisic Milica 
Published: March 2024

AbstractCells and tissues in their native environment are organized into intricate fractal structures, which are rarely recapitulated in their culturein vitro. The extent to which fractal patterns that resemble complex topography in vivo influence cell maturation, and the cellular responses to such shape stimulation remain inadequately elucidated. Yet, the application of fractal cues (topographical stimulation via self-similar patterns) as an external input may offer a much-needed solution to the challenge of improving the differentiated cell phenotypein vitro. Here, we established fractality in podocytes, branching highly differentiated kidney cells, and glomerulus structure. Biomimetic fractal patterns derived from glomerular histology were used to generate topographical (2.5-D) substrates for cell culture. Podocytes grown on fractal topography were found to express higher levels of functional markers and exhibit enhanced cell polarity. To track morphological complexities of differentiated podocytes, we employed a fluorescent labelling assay where labelled individual cells are tracked within otherwise optically silent confluent cell monolayer to reveal cell-cell interdigitation. RNAseq analysis suggests enhanced ECM deposition and remodeling in podocytes grown on fractal topography compared to flat surface or non-fractal microcurvature, mediated by YAP signaling. The incorporation of fractal topography into standard tissue culture well plates as demonstrated here may serve as a user-friendly bioengineered platform for high-fidelity cell culture.
High-frequency extracellular spiking in electrically-active cancer cells
Authors: Melikov Rustamzhon , De Angelis Francesco , Moreddu Rosalia 
Published: March 2024

AbstractMicroelectrode matrices have been extensively used in the past 30 years as a reliable platform to record the extracellular activity of cells traditionally regarded to as excitable, i.e. brain cells and muscle cells. Meanwhile, fundamental biology studies on cancer cells since the 1970s reveal that they exhibit altered functionalities of ion channels, membrane potentials, metabolism, and communication mechanisms when compared to their healthy counterparts. In this work, we present for the first time the presence of extracellular voltage spikes occurring at high frequencies (0.1-3.5 kHz) in breast cancer cells, resembling the ones observed in excitable cells, and the possibility to record them with 30 µm TiN microelectrode matrices. These preliminary findings may open a new path for exploration in a variety of research fields, enabling the access to bioelectrical dynamics in cancer cells and cell networks, targeting bioelectricity as a tool in anticancer drug development and cancer diagnostics, as well as provide a market expansion for companies commercializing microelectrodes and microelectrode recording systems.
Neuronal activity promotes axonal node-like clustering prior to myelination and remyelination in the central nervous system
Authors: Ronzano Rémi , Perrot Clément , Mazuir Elisa , Thetiot Melina , Aigrot Marie-Stéphane , Stheneur Paul , Lejeune François-Xavier , Stankoff Bruno , Lubetzki Catherine , Sol-Foulon Nathalie , Desmazières Anne 
Published: March 2024

ABSTRACTNodes of Ranvier ensure the fast saltatory conduction along myelinated axons, through their enrichment in voltage-gated sodium and potassium channels. We and others have shown that node-like cluster assembly can occur before myelination. In multiple sclerosis, demyelination is associated with node of Ranvier disassembly, but node-like reassembly can occur prior to remyelination. Given the crucial role of neuronal activity in inducing (re)myelination, we asked whether neuronal activity could regulate node-like clustering.We show that node-like clustering is promoted by neuronal activity and decreased when excitatory glutamatergic receptors are inhibited. Altering glutamatergic neurotransmission leads to the downregulation of Nav1.1 expression, which we show to be critical for node-like clustering. Neuronal activity also promotes node-like clustering in remyelination. As node-like clusters modulate conduction velocity and myelination initiation along axons, we propose that activity-dependent node-like clustering could modulate neuronal network establishment, as well as myelination regulation and patterning during development, plasticity and repair.
Naturalistic Object Representations Depend on Distance and Size Cues
Authors: Fairchild Grant T. , Holler Desiree E. , Fabbri Sara , Gomez Michael A. , Walsh-Snow Jacqueline C. 
Published: March 2024

AbstractEgocentric distance and real-world size are important cues for object perception and action. Nevertheless, most studies of human vision rely on two-dimensional pictorial stimuli that convey ambiguous distance and size information. Here, we use fMRI to test whether pictures are represented differently in the human brain from real, tangible objects that convey unambiguous distance and size cues. Participants directly viewed stimuli in two display formats (real objects and matched printed pictures of those objects) presented at different egocentric distances (near and far). We measured the effects of format and distance on fMRI response amplitudes and response patterns. We found that fMRI response amplitudes in the lateral occipital and posterior parietal cortices were stronger overall for real objects than for pictures. In these areas and many others, including regions involved in action guidance, responses to real objects were stronger for near vs. far stimuli, whereas distance had little effect on responses to pictures—suggesting that distance determines relevance to action for real objects, but not for pictures. Although stimulus distance especially influenced response patterns in dorsal areas that operate in the service of visually guided action, distance also modulated representations in ventral cortex, where object responses are thought to remain invariant across contextual changes. We observed object size representations for both stimulus formats in ventral cortex but predominantly only for real objects in dorsal cortex. Together, these results demonstrate that whether brain responses reflect physical object characteristics depends on whether the experimental stimuli convey unambiguous information about those characteristics.Significance StatementClassic frameworks of vision attribute perception of inherent object characteristics, such as size, to the ventral visual pathway, and processing of spatial characteristics relevant to action, such as distance, to the dorsal visual pathway. However, these frameworks are based on studies that used projected images of objects whose actual size and distance from the observer were ambiguous. Here, we find that when object size and distance information in the stimulus is less ambiguous, these characteristics are widely represented in both visual pathways. Our results provide valuable new insights into the brain representations of objects and their various physical attributes in the context of naturalistic vision.
Diclofenac-eugenol modulation of Kv7 and TRPV1 ion channels
Authors: Rivera-Ruedas Adrián , Medina-Vilchis Alejandro Rafael , Romero-Tovar Juan José , Cristóbal-Mondragón Gema R. , De la Rosa Victor 
Published: March 2024

AbstractPharmacological targeting of ion channels represents a crucial avenue for pain management. Among these, the Kv7 family of ion channels plays a significant role controlling neuronal excitability and the generation and propagation of pain-related nerve impulses, thus mitigating excessive electrical signaling and curtailing the exaggerated transmission of pain signals. Pain management strategies often involve a multimodal approach, combining various medications with distinct mechanisms of action to achieve optimal outcomes. Eugenol possesses a spectrum of biological activities, including analgesic and anti-inflammatory properties. When used in conjunction with the anti-inflammatory drug diclofenac, eugenol demonstrates enhanced analgesic efficacy in animal models. We investigated the effects of diclofenac and eugenol on Kv7 and TRPV1 ion channels, both agents act as Kv7 activators, whereas diclofenac inhibits the TRPV1 current, and eugenol reduce the capsaicin-activated current presumably competing for the same binding site. Eugenol shows a time dependent biphasic effect on acid-activated TRPV1 current, first activating and then a slow decay of the current. When eugenol and diclofenac are used together, they limit the extent of depolarization of cells expressing Kv7 and TRPV1. Our results shed light on the combined effectiveness of eugenol and diclofenac in the treatment of acute pain.
Mechanistic principles of hydrogen evolution in the membrane-bound hydrogenase
Authors: Sirohiwal Abhishek , Gamiz-Hernandez Ana P. , Kaila Ville R. I. 
Published: March 2024

AbstractThe membrane-bound hydrogenase (Mbh) fromPyrococcus furiosusis an archaeal member of the Complex I superfamily. It catalyzes the reduction of protons to H2gas powered by a [NiFe] active site and transduces the free energy into proton pumping and Na+/H+-exchange across the membrane. Despite recent structural advances (1–4), the mechanistic principles of H2catalysis and ion transport in Mbh remain elusive. Here we probe how the redox chemistry drives the proton reduction to H2and how the catalysis couples to conformational dynamics in the membrane domain of Mbh. By combining large-scale quantum chemical density functional theory (DFT) and correlatedab initiowave function methods with atomistic molecular dynamics simulations, we show that the proton transfer reactions required for the catalysis are gated by electric field effects that direct the protons by water-mediated reactions from Glu21Ltowards the [NiFe] site, or alternatively along the nearby His75Lpathway that also becomes energetically feasible in certain reaction steps. These local proton-coupled electron transfer (PCET) reactions induce conformational changes around the active site that provide a key coupling element via conserved loop structures to the ion transport activity. We find that H2forms in a heterolytic proton reduction step, with spin crossovers tuning the energetics along key reaction steps. On a general level, our work showcases the role of electric fields in enzyme catalysis, and how these effects are employed by the [NiFe] active site of Mbh to drive the PCET reactions and ion transport.Significance statementHydrogen (H2) serves as a crucial solar fuel in renewable energy systems that can be efficiently produced by microbial hydrogenases. Here we probe the elusive mechanistic principles underlying the H2production in the ancient membrane-bound hydrogenase (Mbh) from the thermophilic archaeonPyrococcus furiosus. Distinct from other hydrogenases, Mbh not only produces H2, but it couples this activity with ion transport across a membrane that powers the archaeal energy metabolism. Our study elucidates key mechanistic principles underlying H2production and shed light on energy transducing enzymes that led to the evolution of modern mitochondrial respiratory enzymes.
Deep learning based genomic breeding of pest-resistant grapevine
Authors: Gan Yu , Liu Zhenya , Zhang Fan , Xu Qi , Wang Xu , Xue Hui , Su Xiangnian , Ma Wenqi , Long Qiming , Ma Anqi , Huang Guizhou , Liu Wenwen , Xu Xiaodong , Sun Lei , Zhang Yingchun , Liu Yuting , Fang Xinyue , Li Chaochao , Yang Xuanwen , Wei Pengcheng , Fan Xiucai , Zhang Chuan , Zhang Pengpai , Liu Chonghuai , Zhang Zhiwu , Huang Sanwen , Wang Yiwen , Liu Zhongjie , Zhou Yongfeng 
Published: March 2024

AbstractCrop pests have profoundly deleterious effects on crop yield and food security. However, conventional pest control depends heavily on the utilization of insecticides, which develops strong pesticide resistance and concerns of food safety. Crop and their wild relatives display diverse levels of pest resistance, indicating the feasibility for breeding of pest-resistant crop varieties. In this study, we integrate deep learning (DL)/machine learning (ML) algorithms, plant phenomics and whole genome sequencing (WGS) data to conduct genomic selection (GS) of pest-resistance in grapevine. We employ deep convolutional neural networks (DCNN) to accurately calculate the severity of damage by pests on grape leaves, which achieves a classification accuracy of 95.3% (Visual Geometry Group 16, VGG16, for binary trait) and a correlation coefficient of 0.94 in regression analysis (DCNN with Pest Damage Score, DCNN-PDS, for continuous trait). We apply DL models to predict and integrate phenotype (both binary and continuous) along with WGS data from 231 grape accessions, conducting Genome-Wide Association Studies (GWAS). This analysis detects a total of 69 QTLs, encompassing 139 candidate genes involved in pathways associated with pest resistance, including jasmonic acid (JA), salicylic acid (SA), ethylene, and other related pathways. Furthermore, through the combination with transcriptome data, we identify specific pest-resistant genes, such asACA12andCRK3, which play distinct roles in resisting herbivore attacks. Machine learning-based GS demonstrates a high accuracy (95.7%) and a strong correlation (0.90) in predicting the leaf area damaged by pests as binary and continuous traits in grapevine, respectively. In general, our study highlights the power of DL/ML in plant phenomics and GS, facilitating genomic breeding of pest-resistant grapevine.
Alternative silencing states of Transposable Elements in Arabidopsis
Authors: Hure Valentin , Piron-Prunier Florence , Yehouessi Tamara , Vitte Clémentine , Kornienko Aleksandra E. , Adam Gabrielle , Nordborg Magnus , Déléris Angélique 
Published: March 2024

AbstractThe DNA methylation/H3K9me2 and Polycomb-group proteins (PcG)-H3K27me3 pathways have long been considered mutually exclusive and specific to TEs and genes, respectively. However, H3K27me3 can be recruited to many TEs in the absence of DNA methylation machinery and sometimes also co-occur with DNA methylation. In this study, we show that TEs can also be solely targeted by H3K27me3 in wild-type Arabidopsis plants. These H3K27me3-marked TEs not only comprise degenerate relics but also seemingly intact copies that display the epigenetic features of responsive PcG target genes as well as an active H3K27me3 regulation. We also show that H3K27me3 can be deposited on newly inserted transgenic TE sequences in a TE-specific manner indicating that silencing is determined incis. Finally, comparison of Arabidopsis natural accessions reveals the existence of a category of TEs - which we refer to as “bifrons” - that are marked by DNA methylation or H3K27me3 depending on the ecotype. This variation can be linked to intrinsic TE features and totrans- acting factors, and reveals a change in epigenetic status across TE lifespan. Our study sheds light on an alternative mode of TE silencing associated with H3K27me3 instead of DNA methylation in flowering plants. It also suggests dynamic switching between the two epigenetic marks at the species level, a new paradigm that might extend to other multicellular eukaryotes.
Photoelectricity generation from beet juice in a bio-electrochemical cell
Authors: Farber Yair , Rasuli David , Shlosberg Yaniv 
Published: March 2024

AbstractThe world is striving for the development of novel clean energy technologies that can replace the utilization of fossil fuels, and assist in the struggle against climate change. A unique approach that does not involve any carbon emission is bio-photo electrochemical cells (BPECs). This method integrates live organisms with an electrochemical system, while native redox species that exist in the organisms can generate dark and photo electrical current. Such systems were previously shown using photosynthetic micro and macro organisms in which the photocurrent mostly derives from photosynthesis. Another electron source was reported to originate from cherries which consist of pigments and enhance the production of the strong electron donor ascorbic acid under solar irradiation. In this work, we show the ability to produce electrical and photoelectrical current from beet juice. We apply cyclic voltammetry and fluorescence methods to show that among the major components that play a role in the current and photocurrent generation are NADPH and flavins.
LIPIDS MODULATE THE DYNAMICS OF GPCR:β-ARRESTIN INTERACTION
Authors: Gomes Antoniel , Di Michele Michela , Roessner Rita Ann , Damian Marjorie , Bisch Paulo M. , Sibille Nathalie , Louet Maxime , Baneres Jean-Louis , Floquet Nicolas 
Published: March 2024

Abstractβ-arrestins are key privileged molecular partners of G-Protein Coupled Receptors (GPCRs), triggering not only their desensitization but also intracellular signaling. Existing structures point to a high conformational plasticity of β-arrestin:GPCRs interaction, with two completely different orientations between receptor and β-arrestin. The same set of structures also indicates that the C-edge loop of β-arrestin could contribute to its anchoring to the membrane, through an interaction with specific lipids, namely PI(4,5)P2. Combining molecular dynamics simulations and fluorescence spectroscopy, we show that β-arrestin 1 interacts with membranes even in the absence of a receptor, an interaction that is enhanced by PI(4,5)P2 presumably holding the β-arrestin 1 C-edge loop into the lipid bilayer. This key interaction helps β-arrestin 1 to adopt a “receptor ready” orientation. As a consequence, PI(4,5)P2 also favors the coupling of β-arrestin 1 to the ghrelin receptor (GHSR). In addition, we show that β-arrestin can adopt the two known extreme orientations when complexed with GHSR. Of importance, PI(4,5)P2 shifts the equilibrium between the two different arrangements, favoring one of them. Simulations performed on the GHSR:β-arrestin complex suggest that release of the C-edge loop is required for these transitions to occur and point to a different distribution of PI(4,5)P2 around the complex depending on the orientation of receptor-bound arrestin. Taken together, our results highlight how PI(4,5)P2 plays a true third player role in the β-arrestin:GPCRs interaction, not only by preparing β-arrestin for its further interaction with receptors but also by modulating its orientation once the protein:protein complex is formed.