bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introducing multifactorial electroculturomics: Alternating Current Electric Pulses, combined with mild thermal treatment, exhibit antimicrobial or stimulatory effects on bacterial pathogens and enteroviruses, implying prospects for targeted microbiomics applications
Authors: Spanou Grigoria , Daskou Maria , Kambouris Manousos E. , Mitsagga Chrysanthi , Mossialos Dimitris , Velegraki Aristea , Patrinos George P. , Giavasis Ioannis 
Published: November 2023

ABSTRACTAIMSTo surrogate chemical and high-energy microbicidals, Electroceuticals may be used as a stand-alone or combined treatment under the guise of Electroculturomics.METHODS AND RESULTSUsing high and low settings of Intensity and Frequency of a medical-rated instrument (TENS) of alternating current the viability and propagation of seven pathogenic bacteria and one enterovirus of environmental and medical importance were testedin vitro, in order to establish the interaction of electroceuticals and mild pasteurization protocols and identify potential synergies and/or antagonism of these treatments. The combined regimen showed synergy, following the prerogatives of the Bioelectric Effect, and antagonism. High frequency (800Hz) rather than low (2 Hz) seems detrimental, while intensity (10 or 1 mA) seems almost inconsequential, while longer sessions enhance detrimental effects but short exposure may be beneficial.CONCLUSIONSNo single treatment seems optimal for all tested bacteria. High frequency can be effective against low titers of Enterovirus, but at higher titers, the effect may be reversed. Case-specific effects on microbial growth patterns seem to be the norm.SIGNIFICANCE AND IMPACT OF STUDYDiverse mechanisms of microbicidal or stimulatory activity are implied, allowing individualized uses and targeted applications in food and environmental safety, therapeutics and industrial bioprocessing.
Mechanism of high energy efficiency of carbon fixation by sulfur-oxidizing symbionts revealed by single-cell analyses and metabolic modeling
Authors: Kleiner M. , Polerecky L. , Lott C. , Bergin C. , Häusler S. , Liebeke M. , Wentrup C. , Musat N. , Kuypers M. M. M. , Dubilier N. 
Published: November 2023

SummaryIn chemosynthetic symbioses between marine invertebrates and autotrophic sulfur-oxidizing bacteria the symbionts feed their host by producing organic compounds from CO2using reduced sulfur compounds as an energy source. One such symbiosis, the gutless marineworm Olavius algarvensisharbors at least five bacterial symbionts of which four have the genetic potential for an autotrophic metabolism.In this study we combined single-cell analyses of CO2fixation, CO2release and bulk uptake, with measurements of O2respiration, sulfur content, and polyhydroxyalkanoate content, as well as mathematical modelling to investigate how energy derived from sulfur oxidation drives carbon fluxes within the symbiosis and between the holobiont and its habitat. We found that under aerobic conditions without external energy sources only the primary symbiont,Ca. Thiosymbion algarvensis, fixed carbon. This symbiont relied on internal sulfur storage for energy production. Our model showed that the apparent efficiency of carbon fixation driven by sulfur oxidation in the symbiosis was higher than thermodynamically feasible if only stored sulfur was considered as source of energy and reducing equivalents. The model and additional calculations showed that reducing equivalents must be derived from a different source than energy. We identified the large amounts of polyhdroxyalkanoate stored by the symbiont as the likely source of reducing equivalents for carbon fixation in the symbiont which boosts the yield of sulfur-driven carbon fixation. The model also showed that heterotrophic carbon fixation by host tissue is not negligible and has to be considered when assessing transfer of carbon from the symbionts to the host.
Sexual History Was One Of The Least Frequently Documented Social History In Cerner PowerChart Histories: A Multi-Hospital Medical Center Experience For The Year 2022
Authors: Gupta Deepak 
Published: November 2023

AbstractBackgroundAs sexual history encompasses sensitive information about private lives, patients as well as providers may find it difficult to discuss during patient-provider encounters.ObjectivesTo ascertain the incidence of absent documentation about sexual history among patients at seven adult hospitals of a multi-hospital medical center during the year 2022.Materials and MethodsThe multi-hospital medical center information technology team ran a search query in electronic medical records to extract census of unique patient identifications quantifying absent documentation rates about social history categories of Tobacco, Alcohol, Substance Abuse, Home/Environment, Sexual, Nutrition/Health, Exercise, Employment/School, Other.ResultsAmong the patients managed in the year 2022 (n=25005), Other and Sexual social history categories were least frequently documented (1-2%). Contrarily, Home/Environment and Tobacco social history categories were most frequently documented (81-82%).ConclusionAmong the patients managed at the multi-hospital medical center, sexual history was one of the least frequently documented social history during the year 2022.
Characterization of tomatocanal-1mutant using a multi-omics approach
Authors: Ahchige Micha Wijesingha , Fisher Josef , Sokolowska Ewelina , Lyall Rafe , Illing Nicola , Skirycz Aleksandra , Zamir Dani , Alseekh Saleh , Fernie Alisdair R. 
Published: November 2023

SummaryThe recently describedcanal-1tomato mutant, which has a variegated leaf phenotype, has been shown to affect canalization of yield. The corresponding protein is orthologous to AtSCO2 - SNOWY COTYLEDON2, which has suggested roles in thylakoid biogenesis. Here we characterize thecanal-1mutant through a multi-omics approach, by comparing mutant to wild-type tissues. While whitecanal-1leaves are devoid of chlorophyll, green leaves of the mutant appear wild-type-like, despite an impaired protein function. Transcriptomic data suggest that green mutant leaves compensate for this impaired protein function by upregulation of transcription of photosystem assembly and photosystem component genes, thereby allowing adequate photosystem establishment, which is reflected in their wild-type-like proteome. Whitecanal-1leaves, however, likely fail to reach a certain threshold enabling this overcompensation, and plastids get trapped in an undeveloped state, while additionally suffering from high light stress, indicated by the overexpression of ELIP homolog genes. The metabolic profile of white and to a lesser degree also green tissues revealed upregulation of amino acid levels, that was at least partially mediated by transcriptional and proteomic upregulation. These combined changes are indicative of a stress response and suggest that white tissues behave as carbon sinks. In summary, our work demonstrates the relevance of the SCO2 protein in both photosystem assembly and as a consequence in the canalization of yield.Significance statementThe variegatedcanalized-1tomato mutant was recently described and the underlying geneSCO2suggested to be a yield canalization gene. Through a multi-omics approach we show that mutants require a transcriptional upregulation of photosystem components and assembly components, likely as overcompensation for partially impaired SCO2 function, to produce a wild type-like proteome and functional photosynthetic tissue Our data, furthermore, suggest that variation of green to white leaf area from plant to plant leads to the yield variation.
Comparative phenotyping of mice reveals canonical and noncanonical physiological functions of TRα and TRβ
Authors: Hönes GS , Geist D , Wenzek C , Pfluger PT , Müller TD , Aguilar-Pimentel A , Amarie OV , Becker L , Dragano N , Garrett L , Hölter SM , Rathkolb B , Rozman J , Spielmann N , Treise I , Wolf E , Wurst W , Fuchs H , Gailus-Durner V , de Angelis MH , Führer D , Moeller LC 
Published: November 2023

AbstractThyroid hormone (TH) effects are mediated through TH receptors (TRs) TRα1, TRβ1, and TRβ2. The TRs bind to thyroid hormone responsive elements on the DNA and regulate expression of TH target genes as ligand dependent transcription factors (canonical signaling). In addition, the TRs α and β mediate activation of signaling pathways, e.g. the PI3K/AKT and MAPK/ERK pathways (noncanonical signaling). Whether such DNA-binding independent TR action contributes to the spectrum of physiological TH effects is largely unknown. The aim of this study was to attribute physiological effects to the two TR isoforms α and β and their canonical and noncanonical signaling. We conducted multi-parameter phenotyping in male and female TR knockout mice (TRαKO, TRβKO), mice with disrupted canonical signaling due to a mutation in the TR DNA-binding domain (TRαGS, TRβGS) and their respective wild-type littermates. Perturbations in senses, especially hearing (mainly TRβ with a lesser impact of TRα), visual acuity and retinal thickness (TRα and TRβ), in muscle metabolism (TRα) and in heart rate (TRα) highlighted the role of canonical TR action. Strikingly, selective abrogation of canonical TR action often had little to no phenotypic consequence, suggesting that noncanonical TR action sufficed to maintain the wild-type phenotype for specific effects. For instance, macrocytic anemia, reduced retinal vascularization or increased anxiety related behavior were only observed in TRαKO, but not TRαGSmice. Noncanonical TRα action increased the efficiency of energy utilization and prevented hyperphagia observed in TRαKOmice. In summary, by examining the phenotypes of TRα and TRβ knockout models alongside their DNA-binding-deficient GS mutants and wildtype counterparts, we could establish that the independent noncanonical actions of TRα and TRβ play a crucial role in modulating sensory, behavioral, and metabolic functions. This comparison underscores the significance of the TRs in orchestrating a spectrum of physiological processes beyond their traditional genomic pathways.
Mapping the gene space at single-cell resolution with gene signal pattern analysis
Authors: Venkat Aarthi , Leone Sam , Youlten Scott E. , Fagerberg Eric , Attanasio John , Joshi Nikhil S. , Perlmutter Michael , Krishnaswamy Smita 
Published: November 2023

AbstractIn single-cell sequencing analysis, several computational methods have been developed to map the cellular state space, but little has been done to map or create embeddings of the gene space. Here, we formulate the gene embedding problem, design tasks with simulated single-cell data to evaluate representations, and establish ten relevant baselines. We then present a graph signal processing approach we callgene signal pattern analysis(GSPA) that learns rich gene representations from single-cell data using a dictionary of diffusion wavelets on the cell-cell graph. GSPA enables characterization of genes based on their patterning on the cellular manifold. It also captures how localized or diffuse the expression of a gene is, for which we present a score called thegene localization score. We motivate and demonstrate the efficacy of GSPA as a framework for a range of biological tasks, such as capturing gene coexpression modules, condition-specific enrichment, and perturbation-specific gene-gene interactions. Then, we showcase the broad utility of gene rep-resentations derived from GSPA, including for cell-cell communication (GSPA-LR), spatial transcriptomics (GSPA-multimodal), and patient response (GSPA-Pt) analysis.
An interdependent Metabolic and Genetic Network shows emergent propertiesin vitro
Authors: Giaveri Simone , Bohra Nitin , Diehl Christoph , Ballinger Martine , Paczia Nicole , Glatter Timo , Erb Tobias J. 
Published: November 2023

AbstractA hallmark of all living organisms is their ability for self-regeneration which requires a tight integration of metabolic and genetic networks. Here we constructed a metabolic and genetic linked in vitro network (MGLN) that shows life-like behavior outside of a cellular context and generates its own building blocks from non-living matter. To this end, we integrated the metabolism of the crotonyl-CoA/ethyl-malonyl-CoA/hydroxybutyryl-CoA (CETCH) cycle with cell-free protein synthesis using recombinant elements (PURE). We demonstrate that the MGLN produces the essential amino acid glycine from inorganic carbon (CO2), and incorporates it into target proteins following DNA-encoded instructions. By programming genetically encoded response into metabolic networks our work opens new avenues for the development of advanced biomimetic systems with emergent properties, including decision-making, self-regeneration and evolution.
Learning sequence, structure, and function representations of proteins with language models
Authors: Hamamsy Tymor , Barot Meet , Morton James T. , Steinegger Martin , Bonneau Richard , Cho Kyunghyun 
Published: November 2023

AbstractThe sequence-structure-function relationships that ultimately generate the diversity of extant observed proteins is complex, as proteins bridge the gap between multiple informational and physical scales involved in nearly all cellular processes. One limitation of existing protein annotation databases such as UniProt is that less than 1% of proteins have experimentally verified functions, and computational methods are needed to fill in the missing information. Here, we demonstrate that a multi-aspect framework based on protein language models can learn sequence-structure-function representations of amino acid sequences, and can provide the foundation for sensitive sequence-structure-function aware protein sequence search and annotation. Based on this model, we introduce a multi-aspect information retrieval system for proteins, Protein-Vec, covering sequence, structure, and function aspects, that enables computational protein annotation and function prediction at tree-of-life scales.
Optimal investments in private land conservation depend more on landholder preferences than climate change
Authors: Williams Brooke A. , Archibald Carla L. , Brazill-Boast James , Drielsma Michael J. , Thapa Rajesh , Love Jamie , Cho Frankie H. T. , Lunney Daniel , Fitzsimons James A. , Iftekhar Sayed , Villarreal-Rosas Jaramar , Bekessy Sarah , Hetherington Scott Benitez , McAlpine Clive A. , Beaumont Linda , Thonell Jillian , Rhodes Jonathan R. 
Published: November 2023

AbstractEffective private land conservation strategies that consider both landholder preferences and future climatic conditions are critical for preserving biodiversity and ecosystem services. Yet, the interaction and relative importance of these factors for conservation planning performance is unknown. Here, we assess the importance of considering landholder preferences and climate change for prioritising locations for conservation tenders to recruit landholders for conservation covenants. To achieve this we develop a planning framework that accounts for the tender process to optimise investment across regions and apply it to koala-focused tenders in New South Wales (NSW), Australia, exploring four planning approaches that consider or are ignorant to landholder preferences and the tender process and/or climate change. We find that optimal investments depend more on landholder preferences than climate change, and when landholder preferences are ignored, there is little benefit in accounting for climate change. Our analysis reveals new insights into this important interaction.
Moving as a group imposes constraints on the energetic efficiency of movement
Authors: Klarevas-Irby James A. , Nyaguthii Brendah , Farine Damien R. 
Published: November 2023

ABSTRACTMovement is a key part of life for both solitary and group-living animals. In solitary animals, the energetic costs of making large displacements can be mitigated by energetically efficient strategies—specifically faster, straighter movements. However, little is known about whether moving as part of a collective enhances or limits the ability for individual group members to express such strategies. Drawing on 6 years of population-level high-resolution (1Hz) GPS tracking of group-living vulturine guineafowl (Acryllium vulturinum), we detected 886 events from 94 tagged individuals where their groups made large displacements, shifting their home ranges in response to changing environmental conditions. We contrasted these movements with data with 94 large displacement events by 19 lone, dispersing individuals. Our results suggest that individuals moving as part of group can significantly reduce their energetic cost of transport when making large displacements (15.5% reduction relative to their normal daily ranging behaviours) by increasing the speed and straightness of their movements. However, even during their most-efficient movements, individuals in groups could not achieve or maintain the same increases in speed that others could when moving alone, resulting in significantly limited efficiency gains (solitary individuals were 34.9% more efficient than individuals in groups). Overall, this study provides evidence for a substantial, and previously hidden, energetic cost arising from collective movement.
Epigenetic Small-Molecule Screen for Inhibition and Reversal of Acinar Ductal Metaplasia in Mouse Pancreatic Organoids
Authors: Atanasova Kalina R. , Perkins Corey M. , Ratnayake Ranjala , Jiang Jinmai , Chen Qi-Yin , Schmittgen Thomas D. , Luesch Hendrik 
Published: November 2023

AbstractBackgroundAcinar ductal metaplasia (ADM) is among the earliest initiating events in pancreatic ductal adenocarcinoma (PDAC) development.MethodsWe developed a novel morphology-based screen using organoids from wildtype and p48Cre/+(Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA).ResultsOf the 144 compounds screened, nine hits and two additional natural product HDAC inhibitors were validated by dose-response analysis. The class I HDAC inhibitors apicidin and FK228, and the histone methyltransferase inhibitor chaetocin demonstrated pronounced ADM inhibition and reversal without inducing significant cytotoxicity at 1 µM. Thioester prodrug class I HDAC inhibitor largazole attenuated ADM while its disulfide homodimer was effective in both ADM inhibition and reversal. Prioritized compounds were validated for ADM reversal in p48Cre/+;LSL-KrasG12D/+(KC) mouse organoids using both morphological and molecular endpoints. Molecular index analysis of ADM reversal in KC mouse organoids demonstrated improved activity compared to TSA. Improved prodrug stability translated into a stronger phenotypic and molecular response. RNA-sequencing indicated that angiotensinogen was the top inhibited pathway during ADM reversal.ConclusionOur findings demonstrate a unique epigenetic mechanism and suggest that the phenotypic screen developed here may be applied to discover potential treatments for PDAC.
Ribosomal RNA synthesis by RNA polymerase I is regulated by premature termination of transcription
Authors: Azouzi Chaïma , Schwank Katrin , Queille Sophie , Kwapisz Marta , Aguirrebengoa Marion , Henras Anthony , Lebaron Simon , Tschochner Herbert , Lesne Annick , Beckouët Frédéric , Gadal Olivier , Dez Christophe 
Published: November 2023

ABSTRACTThe RNA polymerase I (Pol I) enzyme that synthesizes large rRNA precursors, exhibits high rate of pauses during elongation, indicative of a discontinuous process. We show here that Premature Termination of Transcription (PTT) by Pol I is a critical regulatory step limiting rRNA productionin vivo. The Pol I mutant, SuperPol (RPA135-F301S), produces 1.5-fold more rRNA than the wild type (WT). Combined CRAC and rRNA analysis link increased rRNA production in SuperPol to reduced PTT, resulting in shifting polymerase distribution toward the 3’ end of rDNA genes.In vitro, SuperPol shows reduced nascent transcript cleavage, associated with more efficient transcript elongation after pauses. Notably, SuperPol is resistant to BMH-21, a drug impairing Pol I elongation and inducing proteasome- mediated degradation of Pol I subunits. Compared to WT, SuperPol maintains subunit stability and sustains high transcription levels upon BMH-21 treatment. These comparative results show that PTT is alleviated in SuperPol while it is stimulated by BMH-21 in WT Pol I.
Estradiol Mediates Greater Germinal Center Responses to Influenza Vaccination in Female than Male Mice
Authors: Dhakal Santosh , Park Han-Sol , Seddu Kumba , Lee John , Creisher Patrick S. , Davis Kimberly M. , Hernandez Isabella R. , Maul Robert W. , Klein Sabra L. 
Published: November 2023

AbstractAdult females of reproductive ages develop greater antibody responses to inactivated influenza vaccine (IIV) than males. How sex, age, and sex steroid changes impact B cells and durability of IIV-induced immunity and protection over 4-months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center (GC) B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1-4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes determining gene,Sry, was deleted from ChrY and transferred to Chr3, to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.ImportanceFemales of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza was mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females.