bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acclimation temperature and parasite infection drive metabolic changes in a freshwater fish at different biological scales
Authors: Levet Marie , Killen Shaun S. , Bettinazzi Stefano , Mélançon Vincent , Breton Sophie , Binning Sandra A. 
Published: June 2024

AbstractEnvironmental stressors such as elevated temperature and parasite infection can impact individual energy metabolism. However, organismal responses to co-occurring stressors and their effects across biological scales remain unexplored despite the importance of integrative studies for accurately predicting the resilience of natural populations in changing environments.Using wild-caught, naturally parasitized pumpkinseed sunfish, Lepomis gibbosus, we quantified changes in cellular and whole-organism metabolism in response to temperature and parasite infection. We acclimated pumpkinseeds for three weeks at 20°C, 25°C, or 30°C before measuring whole-organism oxygen uptake (ṀO2) using intermittent flow-respirometry to quantify maximal and standard metabolic rates (MMR and SMR, respectively) and aerobic scope (AS). We also measured the maximal activity of enzymes (citrate synthase (CS), respiratory complexes I + III and IV of the electron transport system, and lactate dehydrogenase (LDH)) linked with cellular bioenergetics in fish heart, brain, spleen and gills using spectrophotometry.We found no interactions between acclimation temperatures and parasite intensity on cellular or whole-organism metabolism. However, both stressors were independently related to fish metabolism, with differing impacts across biological scales.Whereas MMR increased with acclimation temperature, this was not mirrored by increasing SMR or decreasing AS, suggesting thermal compensation across acclimation temperatures at the whole-organism level.On a cellular level, acclimation responses were similar across organs, with maximal activity of all enzymes decreasing with increasing acclimation temperature. However, LDH activity remained higher than aerobic enzyme activities (CS, ETS complexes I + III and IV) across acclimation temperatures and organs, especially in gills, where LDH activity drastically increased at 30°C. This may indicate a stronger reliance on anaerobic metabolism to sustain whole-organism metabolic performance.Fish with greater trematode infection had lower MMR and AS. There were no relationships between parasite intensity and SMR nor maximal enzyme activity.Our work shows that co-occurring stressors have distinct impacts on fish metabolism: parasites are primarily related to whole-organism metabolism while temperature impacts metabolism across biological scales. This highlights that interactions among co-occurring stressors are important for ecological realism and accurate predictions regarding population resilience to environmental changes.
B lymphocytes acquire myeloid and autoimmune phenotypes via the downregulation of lymphocyte-specific protein-1
Authors: Lee Naeun , Hong Bong-Ki , You Sungyong , Kwon Riri , Kwon Jihoon , Choi Eunbyeol , Lee Kang-Gu , Kim Yu-Mi , Li Yingjin , Kim Jayhyun , Park Young-Jun , Chung Yeonseok , Im Sin-Hyeog , Sabbagh Laurent , Cho Chul-Soo , Kim Wan-Uk 
Published: June 2024

AbstractActin-binding proteins (ABPs) have been established as important mediators of immune homeostasis, but their effects on lymphocytes are poorly understood. Here, we demonstrated that LSP1, an ABP, is a master regulator for innate immune responses in B lymphocytes.Lsp1deficiency in B cells upregulated the expression of myeloid genes, including CD11b, CD11c, and myeloperoxidase, and bestowed myeloid morphology. Strikingly,Lsp1-deficient B cells exhibited dual functions, namely, strong phagocytic activity and high antibody (Ab) production, like ‘chimera’. The PKCβ-CEBPβ pathway was found to be required for such functional chimerism. Moreover,Lsp1deficiency induced the myeloid B cell phenotype and autoantibody production in B cells and consequently accelerated the progression of experimental lupus in mice. These changes were abrogated by retinoic acid, which upregulated LSP1 expression. In lupus patients, LSP1 expression in B cells was downregulated and inversely correlated with myeloperoxidase (MPO) expression. Overall, this study reveals a new role of the ABP LSP1 in B lymphocytes and emphasizes its critical involvement in promoting autoimmune responses, particularly by generating functionally chimeric B cells.
From Genes to Nanotubes: Exploring the UV-Resistome in the Andean ExtremophileExiguobacteriumSp. S17
Authors: Galván Fátima Silvina , Alonso-Reyes Daniel Gonzalo , Albarracín Virginia Helena 
Published: June 2024

ABSTRACTExiguobacteriumsp. S17, a polyextremophile isolated from modern stromatolites in a High-Altitude Andean Lake, exhibits a remarkable multi-resistance profile against toxic arsenic concentrations, high levels of UV radiation (UV), and elevated salinity. Here, we perform a comprehensive characterization of the mechanisms underlying the UV resistance of S17 (UV-resistome/UVres) through comparative genomics within theExiguobacteriumgenus. Additionally, we describe the morphological and ultrastructural changes in the strain when exposed to different levels of UV.UVresinExiguobacteriumspecies ranges from 112 to 132 genes, with a median of 117. While we anticipatedExiguobacteriumsp. S17 to lead the non-HAAL UVres, it ranked eleventh with 113 genes. This larger UVresinExiguobacteriumspp. aligns with their known adaptation to extreme environments. Morphological and ultrastructural analyses using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) demonstrated significant changes in response to UV exposure in S17 cells. We observed the formation of nanotubes (NTs), a novel finding inExiguobacteriumspp., which increased with higher UV-B doses. These NTs, confirmed to be membranous structures through sensitivity studies and SEM/TEM imaging, suggest a role in cellular communication and environmental sensing. Genomic evidence supports the presence of essential NT biogenesis genes in S17, further elucidating its adaptive capabilities.Our study highlights the complex interplay of genetic and phenotypic adaptations enablingExiguobacteriumsp. S17 to thrive in extreme UV environments. The novel discovery of NTs under UV stress presents a new avenue for understanding bacterial survival strategies in harsh conditions.
Climatic predictors of prominent honey bee (Apis mellifera) disease agents:Varroa destructor,Melissococcus plutonius, andVairimorphaspp
Authors: McAfee Alison , Alavi-Shoushtari Niloofar , Tran Lan , Labuschagne Renata , Cunningham Morgan , Tsvetkov Nadejda , Common Julia , Higo Heather , Pernal Stephen F. , Giovenazzo Pierre , Hoover Shelley E. , Guzman-Novoa Ernesto , Currie Robert W. , Veiga Patricia Wolf , French Sarah K. , Conflitti Ida M. , Pepinelli Mateus , Borges Daniel , Walsh Elizabeth M. , Bishop Christine A. , Zayed Amro , Duffe Jason , Foster Leonard J. , Guarna M. Marta 
Published: June 2024

AbstractImproving our understanding of how climate influences honey bee parasites and pathogens is critical as weather patterns continue to shift under climate change. While the prevalence of diseases vary according to regional and seasonal patterns, the influence of specific climatic predictors has rarely been formally assessed. To address this gap, we analyzed how occurrence and intensity of three prominent honey bee disease agents (Varroa destructor― hereonVarroa―Melissococcus plutonius, andVairimorphaspp.) varied according to regional, temporal, and climatic factors in honey bee colonies across five Canadian provinces. We found strong regional effects for all disease agents, with consistently highVarroaintensity and infestation probabilities and highM. plutoniusinfection probabilities in British Columbia, and year-dependent regional patterns ofVairimorphaspp. spore counts. Increasing wind speed and precipitation were linked to lowerVarroainfestation probabilities, whereas warmer temperatures were linked to higher infestation probabilities. Analysis of an independent dataset shows that these trends forVarroaare consistent within a similar date range, but temperature is the strongest climatic predictor of season-long patterns.Vairimorphaspp. intensity decreased over the course of the summer, with the lowest spore counts found at later dates when temperatures were warm.Vairimorphaspp. intensity increased with wind speed and precipitation, consistent with inclement weather limiting defecation flights. Probability ofM. plutoniusinfection generally increased across the spring and summer, and was also positively associated with inclement weather. These data contribute to building a larger dataset of honey bee disease agent occurrence that is needed in order to predict how epidemiology may change in our future climate.
Stochastic Gene Expression in Proliferating Cells: Differing Noise Intensity in Single-Cell and Population Perspectives
Authors: Zhang Zhanhao , Zabaikina Iryna , Nieto César , Vahdat Zahra , Bokes Pavol , Singh Abhyudai 
Published: June 2024

AbstractRandom fluctuations (noise) in gene expression can be studied from two complementary perspectives: following expression in a single cell over time or comparing expression between cells in a proliferating population at a given time. Here, we systematically investigated scenarios where both perspectives lead to different levels of noise in a given gene product. We first consider a stable protein, whose concentration is diluted by cellular growth, and the protein inhibits growth at high concentrations, establishing a positive feedback loop. For a stochastic model with molecular bursting of gene products, we analytically predict and contrast the steady-state distributions of protein concentration in both frameworks. Although positive feedback amplifies the noise in expression, this amplification is much higher in the population framework compared to following a single cell over time. We also study other processes that lead to different noise levels even in the absence of such dilution-based feedback. When considering randomness in the partitioning of molecules between daughters during mitosis, we find that in the single-cell perspective, the noise in protein concentration is independent of noise in the cell cycle duration. In contrast, partitioning noise is amplified in the population perspective by increasing randomness in cell-cycle time. Overall, our results show that the commonly used single-cell framework that does not account for proliferating cells can, in some cases, underestimate the noise in gene product levels. These results have important implications for studying the inter-cellular variation of different stress-related expression programs across cell types that are known to inhibit cellular growth.
PKA Activity-Driven Modulation of Bidirectional Long-Distance transport of Lysosomal vesicles During Synapse Maintenance
Authors: Badal Kerriann K. , Zhao Yibo , Raveendra Bindu L , Lozano-Villada Sebastian , Miller Kyle E. , Puthanveettil Sathyanarayanan V. 
Published: June 2024

AbstractThe bidirectional long-distance transport of organelles is crucial for cell body-synapse communication. However, the mechanisms by which this transport is modulated for synapse formation, maintenance, and plasticity are not fully understood. Here, we demonstrate through quantitative analyses that maintaining sensory neuron-motor neuron synapses in theAplysiagill-siphon withdrawal reflex is linked to a sustained reduction in the retrograde transport of lysosomal vesicles in sensory neurons. Interestingly, while mitochondrial transport in the anterograde direction increases within 12 hours of synapse formation, the reduction in lysosomal vesicle retrograde transport appears three days after synapse formation. Moreover, we find that formation of new synapses during learning induced by neuromodulatory neurotransmitter serotonin further reduces lysosomal vesicle transport within 24 hours, whereas mitochondrial transport increases in the anterograde direction within one hour of exposure. Pharmacological inhibition of several signaling pathways pinpoints PKA as a key regulator of retrograde transport of lysosomal vesicles during synapse maintenance. These results demonstrate that synapse formation leads to organelle-specific and direction specific enduring changes in long-distance transport, offering insights into the mechanisms underlying synapse maintenance and plasticity.
A small number of point mutations confer formate tolerance inShewanella oneidensis
Authors: Cross Megan C Gruenberg , Aboulnaga Elhussiny , TerAvest Michaela A 
Published: June 2024

AbstractMicrobial electrosynthesis (MES) is a sustainable approach to chemical production from CO2and clean electricity. However, limitations in electron transfer efficiency and gaps in understanding of electron transfer pathways in MES systems prevent full realization of this technology.Shewanella oneidensiscould serve as an MES biocatalyst because it has a well-studied, efficient transmembrane electron transfer pathway. A key first step in MES in this organism could be CO2reduction to formate. However, wild-typeS. oneidensisdoes not tolerate high levels of formate. In this work, we created and characterized formate-tolerant strains ofS. oneidensisfor further engineering and future use in MES systems through adaptive laboratory evolution. Two different point mutations in a sodium-dependent bicarbonate transporter and a DUF2721-contianing protein separately confer formate tolerance toS. oneidensis. The mutations were further evaluated to understand their role in improving formate tolerance. We also show that the wild-type and mutant versions of theS. oneidensissodium-dependent bicarbonate transporter improves formate tolerance ofZymomonas mobilis, indicating the potential for the transfer of this formate tolerance phenotype to other organisms.ImportanceShewanella oneidensisis a bacterium with a well-studied, efficient extracellular electron transfer pathway. This capability could make this organism a suitable host for microbial electrosynthesis using CO2or formate feedstocks. However, formate is toxic toS. oneidensis, limiting the potential for its use in these systems. In this work, we evolve several strains ofS. oneidensisthat have improved formate tolerance and we investigate some mutations that confer this phenotype. The phenotype is confirmed to be attributed to several single point mutations by transferring the wild- type and mutant versions of each gene to the unmutated strain. Finally, the formate tolerance mechanism of one mutation is studied using structural modeling and expression in another host. This study therefore presents a simple method for conferring formate tolerance to bacterial hosts.
Structural basis for transcription activation through cooperative recruitment of MntR
Authors: Shi Haoyuan , Fu Yu , Kodyte Vilmante , Andreas Amelie , Sachla Ankita J. , Miller Keiki , Shrestha Ritu , Helmann John D. , Glasfeld Arthur , Ahuja Shivani 
Published: June 2024

AbstractThe manganese transport regulator (MntR) fromB. subtilisis a dual regulatory protein that responds to heightened Mn2+availability in the cell by both repressing the expression of uptake transporters and activating the expression of efflux proteins. Recent work indicates that, in its role as an activator, MntR binds several sites upstream of the genes encoding Mn2+exporters, leading to a cooperative response to manganese. Here, we use cryo-EM to explore the molecular basis of gene activation by MntR and report a structure of four MntR dimers bound to four 18-base pair sites across an 84-base pair regulatory region of themnePpromoter. Our structures, along with solution studies including mass photometry andin vivotranscription assays, reveal that MntR dimers employ polar and non-polar contacts to bind cooperatively to an array of low-affinity DNA-binding sites. These results reveal the molecular basis for cooperativity in the activation of manganese efflux.
Electrical and G-protein Regulation of CaV2.2 (N-type) Channels
Authors: Nilsson Michelle , Wang Kaiqian , Mínguez-Viñas Teresa , Angelini Marina , Berglund Stina , Olcese Riccardo , Pantazis Antonios 
Published: June 2024

AbstractHow G-proteins inhibit N-type, voltage-gated, calcium-selective channels (CaV2.2) during presynaptic inhibition is a decades-old question. G-proteins Gβγ bind to intracellular CaV2.2 regions, but the inhibition is voltage-dependent. Using the hybrid electrophysiological and optical approach voltage-clamp fluorometry, we show that Gβγ acts by selectively inhibiting a subset of the four different CaV2.2 voltage-sensor domains (VSDs I-IV). During regular “willing” gating, VSDs I and IV activation resemble pore opening, VSD III activation is hyperpolarized, and VSD II appears unresponsive to depolarization. In the presence of Gβγ, CaV2.2 gating is “reluctant”: pore opening and VSD-I activation are strongly and proportionally inhibited, VSD IV is modestly inhibited while VSD III is not. We propose that Gβγ inhibition of VSD-I and -IV underlies reluctant CaV2.2 gating and subsequent presynaptic inhibition.
A novel family of lncRNAs relate facioscapulohumeral muscular dystrophy to nucleolar architecture and protein synthesis
Authors: Salsi Valentina , Losi Francesca , Fosso Bruno , Ferrarini Marco , Pini Sara , Manfredi Marcello , Vattemi Gaetano , Mongini Tiziana , Maggi Lorenzo , Pesole Graziano , Henras Anthony K. , Kaufman Paul D. , McStay Brian , Tupler Rossella 
Published: June 2024

ABSTRACTFacioscapulohumeral muscular dystrophy (FSHD) is a hereditary myopathy linked to deletions of the tandemly arrayed D4Z4 macrosatellite repeats at human chromosome 4q35. These deletions accompany local chromatin changes and the anomalous expression of nearby transcriptsFRG2A, DBET,andD4Z4.We discovered thatFRG2Ais one member of a family of long non-coding RNAs (lncRNAs) expressed at elevated levels in skeletal muscle cells with distinct amounts detected in individual patients. We found thatFRG2AlncRNA preferentially associates with rDNA sequences and centromeres and promotes the three-dimensional association of centromeres with the nucleolar periphery in FSHD cells. Furthermore, we demonstrate that the elevatedFRG2Aexpression in cells from FSHD patients reduces rDNA transcription and global protein synthesis. Our results frame an entirely unanticipated new disease model in which elevated lncRNAs levels mediated by deletions of D4Z4 macrosatellite repeats leads to a diminished protein synthesis capacity, thereby contributing to muscle wasting.
Cell type-specific inhibitory modulation of sound processing in the auditory thalamus
Authors: Rolón-Martínez S. , Mendoza A.J. , Angeloni C.F. , Vogler N.W. , Chen R. , Vu K. , Haas J.S. , Geffen M.N. 
Published: June 2024

ABSTRACTInhibition plays an important role in controlling the flow and processing of auditory information throughout the central auditory pathway, yet how inhibition shapes auditory processing in the medial geniculate body (MGB), the key region in the auditory thalamus, is poorly understood. MGB gates the flow of auditory information to the auditory cortex, and it is inhibited largely by the thalamic reticular nucleus (TRN). The TRN comprises two major classes of inhibitory neurons: parvalbumin (PVTRN)-positive and somatostatin (SSTTRN)-positive neurons. PV and SST neurons have been shown to play differential roles in controlling sound responses in other brain regions. In the somatosensory and visual subregions of the TRN, PVTRNand SSTTRNneurons exhibit anatomical and functional differences. However, it remains unknown whether and how PVTRNand SSTTRNneurons differ in their anatomical projections from the TRN, and whether and how they differentially modulate activity in the vMGB. We find that PVTRNand SSTTRNneurons exhibit differential projection patterns within the thalamus: PVTRNneurons predominantly project to vMGB, whereas SSTTRNneurons project to the dorso-medial regions of MGB. Furthermore, PVTRNand SSTTRNneurons bi-directionally modulate sound responses in MGB. Selective optogenetic inactivation of PVTRNneurons increased sound-evoked activity in over a third of MGB neurons, while another large fraction of neurons showed suppressed activity. In contrast, inactivating SSTTRNneurons largely reduced tone-evoked activity in vMGB neurons. Cell type-specific computational models identified candidate circuit mechanisms for generating the bi-directional effects of TRN inactivation on MGB sound responses. These distinct inhibitory pathways within the auditory thalamus reveal a cell type-specific role for thalamic inhibition in auditory computation.
Neuronal networks quantified as vector fields
Authors: Szeier Szilvia , Jörntell Henrik 
Published: July 2024

AbstractThe function of the brain function is defined by the interactions between its neurons. But these neurons exist in tremendous numbers, are continuously active and densely interconnected. Thereby they form one of the most complex dynamical systems known and there is a lack of approaches to characterize the functional properties of such biological neuronal networks. Here we introduce an approach to describe these functional properties by using its activity-defining constituents, the weights of the synaptic connections and the current activity of its neurons. We show how a high-dimensional vector field, which describes how the activity distribution across the neuron population is impacted at each instant of time, naturally emerges from these constituents. We show why a mixture of excitatory and inhibitory neurons and a diversity of synaptic weights are critical to obtain a network vector field with a structural richness. We argue that this structural richness is the foundation of activity diversity in the brain and thereby an underpinning of the behavioral flexibility and adaptability that characterizes biological creatures.
regulaTER: An R Library to Study the Regulatory Roles of Transposable Elements
Authors: Eskier Doğa , Yetkin Seray , Arslan Nazmiye , Karakülah Gökhan , Alotaibi Hani 
Published: July 2024

AbstractGene expression is regulated at the transcriptional and translational levels and a plethora of epigenetic mechanisms. Regulation of gene expression by transposable elements is well documented. However, a comprehensive analysis of their regulatory roles is challenging due to the lack of dedicated approaches to define their contribution. Here, we present regulaTER, a new R library dedicated to deciphering the regulatory potential of transposable elements in given phenotype. regulaTER utilizes a variety of genomics data of any origin and combines gene expression level information to predict the regulatory roles of transposable elements. We further validated its capabilities using data generated from an epithelial-mesenchymal and mesenchymal-epithelial transition cellular model. regulaTER stands out as an essential asset for uncovering the impact of transposable elements on the regulation of gene expression, with high flexibility to perform a range of transposable element-focused analyses. Our results also provided insights on the contribution of the MIR and B element subfamilies in regulating EMT and MET through the FoxA transcription factor family. regulaTER is publicly available and can be downloaded fromhttps://github.com/karakulahg/regulaTER.