bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress-hardening behaviour of biofilm streamers
Authors: Savorana Giovanni , Redaelli Tommaso , Truzzolillo Domenico , Cipelletti Luca , Secchi Eleonora 
Published: October 2024

AbstractBacteria’s ability to withstand mechanical challenges is enhanced in their biofilm lifestyle, where they are encased in a viscoelastic polymer matrix [1]. Under fluid flow, biofilms can form as streamers – slender filaments tethered to solid surfaces and suspended in the flowing fluid [2, 3]. Streamers thrive in environments subjected to intense hydrodynamic stresses, such as medical devices and water filters, often resulting in catastrophic clogging [4]. Their colonisation success may depend on a highly adaptable mechanical response to varying stress conditions, though the evidence and underlying mechanisms of this adaptation remain elusive. Here, we demonstrate that biofilm streamers exhibit a stress-hardening behaviour, with both differential elastic modulus and effective viscosity increasing linearly with external stress. This stress-hardening is consistent across biofilms with different matrix compositions, formed by various bacterial species, and under diverse growth conditions. We further demonstrated that this mechanical response originates from the properties of extracellular DNA (eDNA) molecules [5], which constitute the structural backbone of the streamers. Our findings reveal an instantaneous, purely physical mechanism enabling streamers to adapt to hydrodynamic stresses. Given the ubiquity of eDNA in biofilms [1, 6], this discovery prompts a re-evaluation of its functional role in biofilm mechanics. Moreover, the stress-hardening behaviour may have broad implications for biofilm development, survival, and ecology, paralleling its role in tissues where it regulates processes such as morphogenesis, cancer formation and wound healing [7, 8].
Mammalian chemosensory bile acid detection supports species and gut microbiome evaluation
Authors: Haran Varun , Morimoto Mari , Rouyer Leena S. F. , McDonald Jeffrey G. , Wang Jinxin , Meeks Julian P. 
Published: October 2024

Long abstractThe rodent accessory olfactory system (AOS) detects environmental chemosignals and guides social and survival-oriented behaviors. Fecal bile acids activate neurons in the AOS, potentially serving as mammalian pheromones and kairomones, but few molecules in this large class have been evaluated thus far. We used live volumetric Ca2+imaging to screen naturally occurring bile acids for their capacity to activate peripheral vomeronasal sensory neurons (VSNs). We found that taurine-conjugated bile acids (tauro-BAs), including taurine-conjugates of cholic acid, deoxycholic acid, lithocholic acid, and chenodeoxycholic acid (TCA, TDCA, TLCA, TCDCA, respectively) activate large populations of VSNs at sub-micromolar concentrations. Tauro-BA-sensitive VSNs rarely responded to unconjugated (CA, CDCA, DCA, LCA), glycine-conjugated (GCA, GDCA, GLCA, GCDCA), or keto-conjugated (7-keto DCA, 12-keto DCA, 7-keto LCA) bile acids. Tauro-BA-sensitive VSNs were also insensitive to well-studied sulfated steroids, suggesting tauro-BAs activate vomeronasal receptors that have not yet been de-orphaned. Among the tauro-BAs, TDCA displayed particularly strong potency, activating many VSNs at sub-micromolar concentrations. Tauro-BAs were not detectable in mouse fecal extracts by mass spectrometry, but were found in reptile fecal extracts and germ-free mouse fecal extracts. VSN responses to germ-free and conventional mouse fecal extracts, conjugated bile acids, and tauro-BAs revealed that non-overlapping populations of VSNs respond to germ-free and conventional mouse feces. A subset of VSNs that were activated by germ-free mouse fecal extracts responded to tauro-BAs, whereas VSNs responsive to conventionally fecal extracts responded to unconjugated bile acids.In vivoexposure to TDCA alone, and to mouse fecal extracts spiked with TDCA, elicited mild aversion and stress-associated behaviors in a non-social context (avoidance, digging, grooming, etc.). These studies establish tauro-BAs as a novel class of aversive vomeronasal ligands that vary in feces across species and gut microbiomes.Short abstractThe rodent accessory olfactory system (AOS) detects environmental chemosignals and guides social and survival-oriented behaviors. Fecal bile acids activate neurons in the AOS, but the full repertoire of bile acids that activate VSNs is not known. A live Ca2+imaging screen revealed that VSNs were highly activated by taurine-conjugated bile acids (tauro-BAs) at sub-micromolar concentrations. Tauro-BAs were undetectable in conventionally raised mouse fecal extracts, but were found in reptile fecal extracts and germ-free mouse fecal extracts. VSN activity to tauro-BAs overlapped that of germ-free mouse fecal extracts, suggesting a link between bile acid chemosensation and the gut microbiome. When mice were exposed to taurodeoxycholic acidin vivo, they displayed mild aversion and stress-associated behaviors.
Melanocyte differentiation and mechanosensation are differentially modulated by distinct extracellular matrix proteins
Authors: Luthold Carole , Didion Marie , Benedum Emilio , Burkhart Ann-Kathrin , Demmerle Nina , Gunaratnam Gubesh , Rácz Vanessa Samira , Bischoff Markus , Ridzal Annika , Iden Sandra 
Published: October 2024

ABSTRACTDysfunctions in melanocytes can lead to pigmentation disorders, such as albinism, or contribute to the development of melanoma, the most aggressive form of skin cancer. Epidermal melanocytes typically interact with the collagen IV-rich basement membrane, but upon injury or in pathological conditions, they can encounter environments rich in collagen I or fibronectin. While alterations in ECM composition and stiffness are known to impact cell behavior, the specific roles of each of these cues for melanocyte functions remain unclear. To explore the impact of these extrinsic cues, we here exposed murine melanocytes to different ECM proteins as well as varying substrate stiffnesses. This study identified MITF, a key regulator of melanocyte differentiation and function, as an ECM- and mechanosensitive transcription factor. We further revealed that distinct ECM proteins and substrate stiffness engage a MEK/ERK/MITF signaling axis to control melanocyte functions. Exposure of melanocytes to collagen I restricted ERK activation, promoting high nuclear MITF levels associated with melanocyte proliferation and differentiation. Conversely, fibronectin elicited elevated ERK activation, leading to low nuclear MITF, correlating with a dedifferentiated and motile phenotype. Importantly, inhibiting ERK activity in melanocytes cultured on fibronectin led to increased MITF nuclear localization, MITF target gene expression and enhanced melanogenesis. Additionally, we uncovered that melanocyte mechanoresponses differ depending on the specific ECM environment. Together, these findings reveal a synergistic effect of extrinsic cues on melanocyte function, with a context-dependent MITF regulation downstream of ERK, offering new perspectives for our understanding of melanocyte-related pathologies.
Universal rules govern plasmid copy number
Authors: Ramiro-Martínez Paula , de Quinto Ignacio , Gama João Alves , Rodríguez-Beltrán Jerónimo 
Published: October 2024

AbstractPlasmids –autonomously replicating DNA molecules– are pervasive in the microbial world, where they fuel evolution as key vehicles for gene transfer. Plasmids are as diverse as their hosts and exhibit a broad range of replication and mobility strategies, genetic repertoires, host ranges, sizes, and copies per cell. While most of these features have been extensively characterized, the determinants of plasmid copy number (PCN) remain poorly understood. Here, we leveraged extensive DNA sequencing data to comprehensively analyze the copy number of thousands of diverse bacterial plasmids. We found that the copy number of natural plasmids is highly variable, spanning nearly three orders of magnitude, and that it is intrinsically robust against changes in genomic context. We further show that PCN variability is tightly associated with plasmid lifestyles and develop the concept of replicon dominance to explain interactions in widespread multi-replicon plasmids. Finally, we uncover a universal scaling law that links copy number and plasmid size across phylogenetic boundaries, indicating that pervasive constraints orchestrate the PCN-size trade-off. Altogether, our work pioneers large-scale analyses of PCN while uncovering the fundamental rules that govern plasmid biology.
A ubiquitous and diverse methanogenic community drives microbial methane cycling in eutrophic coastal sediments
Authors: Wallenius A.J. , Venetz J. , Zygadlowska O.M. , Lenstra W.K. , van Helmond N.A.G.M. , Dalcin Martins P. , Slomp C.P. , Jetten M.S.M. 
Published: October 2024

AbstractCoastal areas are responsible for over 75% of global marine methane emissions and this proportion is predicted to grow due to an increase in anthropogenically induced eutrophication and deoxygenation. Prolonged periods of low oxygen and high organic matter input have been put forward to cause an imbalanced microbial methane cycle, as methane oxidation cannot keep up with methane production. However, it is still unclear what factors affect each process and which microorganisms are responsible. Here we show that methanogenic processes dominate microbial methane cycling in the anoxic sediments of marine Lake Grevelingen (NL) after summer stratification with bottom water anoxia. We observed a shallow and narrow sulfate-methane transition zone between 5 and 15 cm depth, with high methane concentrations (> 5 mM) below this zone. Methanogenesis was dominant over methanotrophy in all investigated layers as active methanogenesis potential was detected down to 60 cm below sea floor, but methane oxidation was only observed in a narrow section of the sulfate-methane transition zone. Based on amplicon sequencing and sediment incubations, we uncovered a metabolically and phylogenetically diverse methanogenic community with distinct niche separation in different sediment layers. ANME archaea and their putative syntrophic sulfate-reducing bacteria were restricted to a narrow zone and were co-occurring with the detected methane oxidation activity. Our results suggest that eutrophication and deoxygenation will further contribute to rising methane emissions in coastal areas, as the microbial methane cycle will be tilted towards increased methanogenesis while the efficiency of the microbial methane filter is expected to decline.
Systems genetic dissection of Alzheimer’s disease brain gene expression networks
Authors: Zhao Pinghan , Fadel Omar El , Le Anh , Mangleburg Carl Grant , Dhindsa Justin , Wu Timothy , Zhao Jinghan , Huang Meichen , Amoh Bismark , Marella Aditi Sai , Li Yarong , Seyfried Nicholas T. , Levey Allan I. , Liu Zhandong , Al-Ramahi Ismael , Botas Juan , Shulman Joshua M 
Published: October 2024

ABSTRACTIn Alzheimer’s disease (AD), changes in the brain transcriptome are hypothesized to mediate the impact of neuropathology on cognition. Gene expression profiling from postmortem brain tissue is a promising approach to identify causal pathways; however, there are challenges to definitively resolve the upstream pathologic triggers along with the downstream consequences for AD clinical manifestations. We have functionally dissected 30 AD-associated gene coexpression modules using a cross-species strategy in fruit fly (Drosophila melanogaster) models. Integrating longitudinal RNA-sequencing and behavioral phenotyping, we interrogated the unique and shared transcriptional responses to amyloid beta (Aβ) plaques, tau neurofibrillary tangles, and/or aging, along with potential links to progressive neuronal dysfunction. Our results highlight hundreds of conserved, differentially expressed genes mapping to human AD regulatory networks. To confirm causal modules and pinpoint AD network drivers, we performed systematicin vivogenetic manipulations of 357 conserved, prioritized targets, identifying 141 modifiers of Aβ- and/or tau-induced neurodegeneration. We discover an up-regulated network that is significantly enriched for both AD risk variants and markers of immunity / inflammation, and which promotes Aβ and tau-mediated neurodegeneration based on fly genetic manipulations in neurons. By contrast, a synaptic regulatory network is strongly downregulated in human brains with AD and is enriched for loss-of-function suppressors of Aβ/tau inDrosophila. Additional experiments suggest that this human brain transcriptional module may respond to and modulate Aβ-induced glutamatergic hyperactivation injury. In sum, our cross-species, systems genetic approach establishes a putative causal chain linking AD pathology, large-scale gene expression perturbations, and ultimately, neurodegeneration.
Heterogeneity in chromatin structure drives core regulatory pathways in B-cell Acute Lymphoblastic Leukemia
Authors: Sen Arko , Xu Zhichao , Tyndale Sélène T. , Yasis Jean , Cho Chae Yun , Bump Rosalind , Chandran Sahaana , Luo Linda , Fu Yi , Petersen Lillian Kay , Shokhirev Max , Kuo Dennis J. , McVicker Graham , Dixon Jesse R. 
Published: October 2024

AbstractB-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Based on gene expression profiling, B-ALL can be classified into distinct transcriptional subtypes with differing disease outcomes. Many of these transcriptional subtypes are defined by mutations in transcription factors and chromatin-modifying enzymes, but how such diverse mutations lead to distinct transcriptional subtypes remains unclear. To illuminate the chromatin regulatory landscape in B-ALL, we analyzed 3D genome organization, open chromatin, and gene expression in 53 primary patient samples. At the level of 3D genome organization, we identified chromatin interactions that vary across transcriptional subtypes. These sites of variable 3D chromatin interactions correlate with local gene expression changes and are enriched for core drivers of B-ALL observed in genome-wide CRISPR knock-out screens. Sites of variable 3D genome interactions are frequently shared across multiple transcriptional subtypes and are enriched for open chromatin sites found in normal B-cell development but repressed in mature B-cells. Within an individual patient sample, the chromatin landscape can resemble progenitor chromatin states at some loci and mature B-cell chromatin at others, suggesting that the chromatin in B-ALL patient tumor cells is in a partially arrested immature state. By analyzing transcriptomic data from large cohorts of B-ALL patients, we identify gene expression programs that are shared across transcriptional subtypes, associated with B-cell developmental stages, and predictive of patient survival. In combination, these results show that the 3D genome organization of B-ALL reflects B-cell developmental stages and helps illustrate how B-cell developmental arrest interacts with transcriptional subtypes to drive B-ALL.
α-Copaene is a potent repellent against the Asian Citrus PsyllidDiaphorina citri
Authors: Magnani Rodrigo Facchini , Volpe Haroldo Xavier Linhares , Luvizotto Rejane Angélica Grigio , Mulinari Tatiana Aparecida , Agostini Thiago Trevisoli , Bastos Jairo Kenupp , Ribeiro Victor Pena , Carmo-Sousa Michele , Wulff Nelson Arno , Peña Leandro , Leal Walter S. 
Published: October 2024

AbstractThe Asian Citrus Psyllid (ACP),Diaphorina citri, severely threatens citrus production worldwide by transmitting the greening(= Huanglongbing)-causing bacteriumCandidatusLiberibacter asiaticus. There is growing evidence that the push-pull strategy is suitable to partially mitigate HLB by repelling ACP with transgenic plants engineered to produce repellents and attracting the vector to plants with a minimal disease transmission rate. Species that pull ACP away from commercial citrus plants have been identified, and transgenic plants that repel ACP have been developed. The concept of a repellent-producing plant was first demonstrated with anArabidopsisline engineered to overexpress a gene controlling the synthesis of β-caryophyllene and other sesquiterpenes. We have analyzed the volatile organic compounds released by thisArabidopsisline and identified α-humulene, α-copaene, and trace amounts of β-elemene, in addition to β-caryophyllene. Behavioral measurements demonstrated that α-copaene repels ACP at doses ca. 100x lower than those needed for β-caryophyllene repellence. In contrast, α-humulene is innocuous at the level emitted by the transgenic plant. We confirmed that a mixture of the three sesquiterpenes in the ratio 100:10:1 repels ACP. Likewise, a commercial sample of refined copaiba oil containing the three sesquiterpenes, in a proportion similar to that in the transgenic plant, repelled ACP.
Estimating Wingbeat Frequency on Hummingbirds using a No-labeling Learning Computer Vision Approach
Authors: Bastidas-Rodriguez Maria Ximena , Fernandes Ana Melisa , Espejo Uribe María José , Abaunza Diana , Roncancio Juan Sebastián , Gutierrez Zamora Eduardo Aquiles , Pai Cristian Flórez , Smiley Ashley , Hurme Kristiina , Clark Christopher J. , Rico-Guevara Alejandro 
Published: October 2024

SynopsisWingbeat frequency estimation is an important aspect for the study of avian flight, energetics, and behavioral patterns, among others. Hummingbirds, in particular, are ideal subjects to test a method for this estimation due to their fast wing motions and unique aerodynamics, which results from their ecological diversification, adaptation to high-altitude environments, and sexually selected displays. Traditionally, wingbeat frequency measurements have been done via “manual” image/sound processing. In this study, we present an automated method to detect, track, classify, and monitor hummingbirds in high-speed video footage, accurately estimating their wingbeat frequency using computer vision techniques and signal analysis. Our approach utilizes a zero-shot learning algorithm that eliminates the need for labeling during training. Results demonstrate that our method can produce automated wingbeat frequency estimations with minimal supervision, closely matching those performed by trained human observers. This comparison indicates that our method can, in some scenarios, achieve low or zero error compared to a human, making it a valuable tool for flight analysis. Automating video analysis can assist wingbeat frequency estimation by reducing processing time and, thus, lowering barriers to analyze biological data on fields such as aerodynamics, foraging behavior, and signaling.
Targeted Degradation of MYC2 through MPK6 Phosphorylation Reveals Mechanisms and Implications for Jasmonic Acid Signaling
Authors: Im Jong Hee , Son Seungmin , Jung Man-Young , Ko Jae-Heung , Han Kyung-Hwan 
Published: October 2024

AbstractMYC2 is a key regulator in the Jasmonic acid (JA) signaling pathway, yet the mechanisms governing its stability remain unclear. In this study, we demonstrate that MYC2 is degraded by MPK6 under JA signaling. Through yeast two-hybrid and co-immunoprecipitation assays, andin vitrokinase assay, we show that MPK6 directly interacts with and phosphorylates MYC2. Additionally, MYC2 transcriptional activity is enhanced in thempk6mutant. Further, MPK6 phosphorylates MYC2 at threonine 328, leading to its degradation. These findings suggest that MPK6 drives MYC2 degradation by specifically phosphorylating threonine 328 within the JA signaling pathway.
Impact of Optogenetic Activation of the Thalamic Reticular Nucleus on Sleep Architecture in Mice
Authors: Arai Mayuko , Tok Sean , Kent Brianne A 
Published: October 2024

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide and is often accompanied by significant sleep disturbances, such as sleep fragmentation, early awakenings, decreased sleep efficiency, and insomnia. It has been suggested that the alterations in activity of the thalamic reticular nucleus (TRN) are closely associated with sleep disruptions in AD. Evidence suggests that activating neurons expressing gamma-aminobutyric acid (GABA) within the TRN may enhance sleep quality and potentially ameliorate neuropathology associated with AD. However, the precise mechanisms through which TRN influences sleep disruptions and AD pathophysiology remain poorly understood. In this study, we investigated whether activating GABAergic TRN neurons could alter sleep architecture in wild-type mice. Utilizing optogenetic stimulation, we observed that activation of these neurons did not significantly alter sleep state durations or delta wave power, a key indicator of Slow Wave Sleep (SWS). Furthermore, the application of a two-virus strategy inadvertently led to non-specific opsin expression beyond the targeted TRN area. We discuss the potential factors that contributed to these outcomes, providing directions for future investigations to better delineate the role of the TRN in sleep and AD.
A genotype-first approach identifies variants for orofacial clefts and other phenotypes in dogs
Authors: Buckley Reuben M , Bilgen Nüket , Harris Alexander C , Savolainen Peter , Tepeli Cafer , Erdoğan Metin , Serres Armero Aitor , Dreger Dayna L , van Steenbeek Frank G , Hytönen Marjo K , Hale Jessica , Lohi Hannes , Çınar Kul Bengi , Boyko Adam R , Ostrander Elaine A 
Published: October 2024

AbstractDog breeding promotes within-group homogeneity through conformation to strict breed standards, and also drives between-group heterogeneity in pursuit of characteristic breed traits. There are over 350 recognized dog breeds that provide the foundation for investigating the genetic basis of phenotypic diversity. Typically, breed standard phenotypes such as stature, fur length, and craniofacial structure are analyzed in genetic association studies. However, such analyses are limited to the assayed phenotypes, leaving difficult to measure phenotypic subtleties potentially overlooked. In this study, the genotype-first approach was adapted to the dog genome to investigate coding variation from over 2000 dogs, leading to discoveries of new mutations related to craniofacial morphology and stature. Breed-enriched variants were prioritized according to gene constraint, which was calculated using a mutation model derived from trinucleotide substitution probabilities in the dog. Among the discovered variants was a splice-acceptor mutation inPDGFRAassociated with bifid nose, a characteristic trait of Çatalburun dogs, implicating the gene’s role in midline closure, and a frameshift mutation inLCORLassociated with large canine body size, thus highlighting the importance of allelic heterogeneity in selection for breed traits. Most priority variants were not associated with genomic signatures for breed differentiation, as these regions were enriched for constrained genes intolerant to nonsynonymous variation, suggesting a model of breed phenotype diversification based on regulatory changes to essential genes. Identification of trait-associated variants in dogs informs new biological roles for genes. Improved collection of breed disease risk data, along with increased breed representation, will drive further discoveries.