bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodiummyo-inositol cotransporter-1, SMIT1, promotes cardiac hypertrophy and fibrosis in pressure overloaded mouse hearts
Authors: Marino Alice , Cumps Julien , Guilbert Laura , Baufays Claire , Ginion Audrey , Ferté Laura , Battault Sylvain , Ambroise Jerome , Bearzatto Bertrand , Zuurbier Coert J. , Lezoualch Frank , Pestiaux Camille , Pyka Grzegorz , Kerckhofs Greet , Tyteca Donatienne , Bouzin Caroline , Bertrand Luc , Horman Sandrine , Beauloye Christophe 
Published: October 2023

AbstractBackgroundSodiummyo-inositol cotransporter-1 (SMIT1) belongs to the sodium-glucose cotransporter (SGLT) family. SMIT1 is expressed in cardiac cells, including fibroblasts and cardiomyocytes. However, the function of SMIT1 in the heart remains unknown.MethodsWe used a model of pressure overload induced by transverse aortic constriction in wild type (WT) mice and mice lacking SMIT1 (Smit1-/-), combined with echocardiography, immunoblot and staining, contrast-enhanced microfocus computed tomography, and RNA-sequencing to evaluate the contribution of SMIT1 in cardiac hypertrophy, fibrosis and function. In addition, we used primary cultures of adult mouse and neonatal rat cardiomyocytes to define the molecular pathways affected by SMIT1.ResultsWe found that aortic banding fails to induce systolic dysfunction, cardiac hypertrophy and fibrosis inSmit1-/-mice, in contrast to WT controls. Deletion of SMIT1 reduces cardiacO-GlcNAcylation and maintains basal levels of Carabin following hemodynamic stress. In the absence of SMIT1, Carabin inhibits calcineurin/NFAT and Ras/ERK1/2 pathways, putting a brake on transcriptional reprogramming and further development of cardiac hypertrophy.In vitro, we showed that the lack of SMIT1 mitigates phenylephrine-induced hypertrophy and calcium increase in isolated cardiomyocytes.ConclusionsThis work establishes SMIT1 as a key driver of hypertrophy, suggesting that pharmacological inhibition of this SGLT member can serve as a potential strategy to prevent or treat pathological hypertrophy and heart failure.Abstract FigureGraphical abstract.Model of the role of SMIT1 in the development of cardiac hypertrophy.We found that SMIT1 modulates intracellular calcium levels, downregulates Carabin and increases OGT expression, to promote pathological cardiac hypertrophy and heart failure development.
Prefrontal activity sharpens spatial sensitivity of extrastriate neurons
Authors: Vanegas M. Isabel , Akbarian Amir , Clark Kelsey L. , Nesse William H. , Noudoost Behrad 
Published: October 2023

AbstractPrefrontal cortex is known to exert its control over representation of visual signals in extrastriate areas such as V4. Frontal Eye Field (FEF) is suggested to be the proxy for the prefrontal control of visual signals. However, it is not known which aspects of sensory representation within extrastriate areas are under the influence of FEF activity. We employed a causal manipulation to examine how FEF activity contributes to spatial sensitivity of extrastriate neurons. Finding FEF and V4 areas with overlapping response field (RF) in two macaque monkeys, we recorded V4 responses before and after inactivation of the overlapping FEF. We assessed spatial sensitivity of V4 neurons in terms of their response gain, RF spread, coding capacity, and spatial discriminability. Unexpectedly, we found that in the absence of FEF activity, spontaneous and visually-evoked activity of V4 neurons both increase and their RFs enlarge. However, assessing the spatial sensitivity within V4, we found that these changes were associated with a reduction in the ability of V4 neurons to represent spatial information: After FEF inactivation, V4 neurons showed a reduced response gain and a decrease in their spatial discriminability and coding capacity. These results show the necessity of FEF activity for shaping spatial responses of extrastriate neurons and indicates the importance of FEF inputs in sharpening the sensitivity of V4 responses.
Measures of population immunity can predict the dominant clade of influenza A (H3N2) in the 2017-2018 season and reveal age-associated differences in susceptibility and antibody-binding specificity
Authors: Kim Kangchon , Vieira Marcos C. , Gouma Sigrid , Weirick Madison E. , Hensley Scott E. , Cobey Sarah 
Published: October 2023

AbstractBackgroundFor antigenically variable pathogens such as influenza, strain fitness is partly determined by the relative availability of hosts susceptible to infection with that strain compared to others. Antibodies to the hemagglutinin (HA) and neuraminidase (NA) confer substantial protection against influenza infection. We asked if a cross-sectional antibody-derived estimate of population susceptibility to different clades of influenza A (H3N2) could predict the success of clades in the following season.MethodsWe collected sera from 483 healthy individuals aged 1 to 90 years in the summer of 2017 and analyzed neutralizing responses to the HA and NA of representative strains using Focus Reduction Neutralization Tests (FNRT) and Enzyme-Linked Lectin Assays (ELLA). We estimated relative population-average and age-specific susceptibilities to circulating viral clades and compared those estimates to changes in clade frequencies in the following 2017-18 season.ResultsThe clade to which neutralizing antibody titers were lowest, indicating greater population susceptibility, dominated the next season. Titer correlations between viral strains varied by age, suggesting age-associated differences in epitope targeting driven by shared past exposures. Yet substantial unexplained variation remains within age groups.ConclusionsThis study indicates how representative measures of population immunity might improve evolutionary forecasts and inform selective pressures on influenza.
Mapping the landscape: A protocol of a jurisdictional scan of self-identified learning health systems
Authors: Vanderhout Shelley , Bird Marissa , Giannarakos Antonia , Whitmore Carly 
Published: October 2023

AbstractBackgroundThere is a growing movement to implement learning health systems (LHS), in which real-time evidence, informatics, patient-provider partnerships and experiences, and organizational culture are aligned to support improvements in care. However, what constitutes a LHS varies based on context and capacity, hindering standardization, scale-up, and knowledge sharing. Further, LHS often use “usual care” as the benchmark for comparing new approaches to care, but disentangling usual care from multifarious care modalities found across settings is challenging. To advance robust LHS, a comprehensive overview of existing LHS including strengths and opportunities for growth is needed.ObjectivesTo scope and identify international existing LHS to: 1) inform the global landscape of LHS, highlight common strengths, and identify opportunities for growth or improvement; and 2) identify common characteristics, emphases, assumptions, or challenges described in establishing counterfactuals in LHS.MethodsA jurisdictional scan will be conducted according to modified PRISMA guidelines. LHS will be identified through a search of peer-reviewed and grey literature using Ovid Medline, Ebsco CINAHL, Ovid Embase, Clarivate Web of Science, and PubMed Non-Medline databases and the web along with informal discussions with peer LHS experts. Self-identified LHS will be included if they are described in sufficient detail, either in literature or during informal discussions, according to ≥4 of 10 criteria (core functionalities, analytics, use of evidence, co-design/implementation, evaluation, change management/governance structures, data sharing, knowledge sharing, training/capacity building, equity, sustainability) in an existing framework to characterize LHS. Search results will be screened, extracted, and analyzed to inform two descriptive reviews pertaining to our two main objectives. Data will be extracted according to a pre-specified extraction form and summarized descriptively.ImplicationsThis research will characterize the current landscape of worldwide LHS and provide a foundation for promoting knowledge and resource sharing, identifying next steps for the growth, improvement, and evaluation of LHS.
Comparative Organ Disease Burden and Sequelae of Influenza and SARS-CoV-2 Infection: An Observational Study Using Real-World Data
Authors: Bartha Istvan , Maher Cyrus , Lavrenko Victor , Boundy Keith , Kinter Elizabeth , Yeh Wendy , Corti Davide , Telenti Amalio 
Published: October 2023

AbstractInfections with SARS-CoV-2 and influenza are associated with acute and post-acute complications and sequelae of many organ systems (i.e., disease burden). It is important to understand the global disease burden that associates with and follows acute infection in order to establish preventive and therapeutic strategies and to reduce the use of health resources and improve patient health outcomes. To address these questions, we utilized the National Covid Cohort Collaborative, which is an integrated and harmonized data repository of electronic health record data in the USA. From this database, we included in analysis 346,648 eligible SARS-CoV-2-infected patients, 78,086 eligible influenza infected patients, and 146,635 uninfected controls. We describe the disease burden that extends over 2-3 months following infection, and we quantify the reduction of disease burden by treatment. We identify a burden of disease following medically attended influenza that is comparable to that of medically attended SARS-CoV-2 infection. However, in contrast to SARS-CoV-2, influenza acute infection and disease burden are not responsive to antiviral treatment and thus remain as an unmet medical need. Focusing therapeutic strategies solely on the short-term management of acute infection may also underestimate the extended health benefits of antiviral treatment.
Lifetime exposure to violence and early cardiometabolic risk factors in a healthy Swedish cohort
Authors: Lynch Rebekka , Aspelund Thor , Fang Fang , Bergstedt Jacob , Hauksdóttir Arna , Arnberg Filip K. , Hrafnkelsdóttir Þórdís Jóna , Pedersen Nancy L. , Valdimarsdóttir Unnur 
Published: October 2023

AbstractIntroductionViolence exposure has been associated with cardiovascular disease. Less is known about underlying mechanisms, including early cardiometabolic risk factors, and possible sex differences of such associations.MethodsWe used data from the Swedish LifeGene study on 23,215 males and females, aged 18-50 years. At baseline (2009-1016) participants answered the Life Stressor Checklist-Revised alongside questions on medical diagnoses of hypertension, diabetes, dyslipidemia and smoking history. At a clinical visit, blood pressure, BMI, glycated hemoglobin (HbA1c), total cholesterol, ApoB/ApoA1 ratio, and high-sensitivity C-Reactive Protein (hs-CRP) were measured. Modified Poisson and linear regression were used to test the association between violence and cardiometabolic risk factors.ResultsAt mean age 33±8 years, lifetime exposure to violence was reported by 23% of females and 15% of males. Those exposed to violence were more likely to smoke (PR 1.86, CI: 1.66–2.07) and report a diagnosis of hypertension (PR 1.39, CI: 1.18-1.64). While no differences were observed in measured systolic blood pressure (B -0.34, CI: -0.70, 0.02), HbA1c (B 0.06, CI: - 0.08, 0.20) or total cholesterol (B -0.01, CI: -0.04, 0.02), both males and females exposed to violence had higher BMI (B 0.51, CI: 0.39–0.63) and hs-CRP (B 0.11, CI: 0.06–0.16), after adjustment. Violence in childhood, as opposed to adulthood, and exposure to both sexual and physical violence, as opposed to either type, was more strongly associated with hs-CRP and BMI.DiscussionIn a young healthy Swedish sample, lifetime exposure to violence was associated with some but not all early cardiometabolic risk factors among both males and females.
Synthetic Peptide Nucleic Acids in Action:In VivoInterference of thegroELGene from Pea Aphid EndosymbiontBuchnera aphidicola
Authors: Tan Kathrine Xin Yee , Shigenobu Shuji 
Published: October 2023

AbstractThe unculturable nature of intracellular obligate symbionts presents a significant challenge for elucidating gene functionality, necessitating the development of gene manipulation techniques. One of the best-studied obligate symbioses is that between aphids and the bacterial endosymbiontBuchnera aphidicola.Given the extensive genome reduction observed inBuchnera, the remaining genes are crucial for understanding the host-symbiont relationship, but a lack of tools for manipulating gene function in the endosymbiont has significantly impeded the exploration of the molecular mechanisms underlying this mutualism. In this study, we introduced a novel gene manipulation technique employing synthetic single-stranded peptide nucleic acids (PNAs). We targeted the criticalBuchnera groELusing specially designed antisense PNAs conjugated to an arginine-rich cell-penetrating peptide (CPP). Within 24 h of PNA administration via microinjection, we observed a significant reduction ingroELexpression andBuchneracell count. Notably, the interference ofgroELled to profound morphological malformations inBuchnera, indicative of impaired cellular integrity. The gene knockdown technique developed in this study, involving the microinjection of CPP-conjugated antisense PNAs, provides a potent approach forin vivogene manipulation of unculturable intracellular symbionts, offering valuable insights into their biology and interactions with hosts.
Seasonal dynamics of the microbial methane filter in the water column of a eutrophic coastal basin
Authors: Venetz Jessica , Żygadłowska Olga M. , Dotsios Nicky , Wallenius Anna J. , van Helmond Niels A.G.M. , Lenstra Wytze K. , Klomp Robin , Slomp Caroline P. , Jetten Mike S.M. , Veraart Annelies J. 
Published: October 2023

AbstractIn the water column of coastal waters, methane-oxidizing bacteria (MOB) can form a methane biofilter. This filter can counteract high benthic methane fluxes and thereby lower methane emissions to the atmosphere. Recent metagenomic studies revealed that the metabolism of the MOB in the filter is versatile, and could quickly respond to changing oxygen concentrations. Changes in oxygen availability in coastal basins are largely driven by seasonal stratification and mixing. However, it is still unclear how well the methane biofilter functions throughout the seasons, and how this relates to MOB community composition. Here, we determined water column methane and oxygen depth profiles and the methanotrophic community structure, methane oxidation potential, and methane fluxes of the Scharendijke basin in marine Lake Grevelingen between March and October 2021. In this period, the methane filter mainly consisted of three MOB belonging toMethylomonadaceae. Although in low relative abundance, the methanotrophic community was present in the mixed water column in March and had increased to 9 % by July in the stratified water column, with a distinct vertical niche partitioning in the redoxcline. The methane and oxygen gradients were vertically decoupled in summer upon the formation of a suboxic zone. Surprisingly, this did not affect the vertical distribution or potential methane oxidation of MOB. Moreover, water-air fluxes remained below 0.6 mmol m-2day-1. Our findings suggest active methane removal by MOB in virtually anoxic water. Weakening of the stratification in September resulted in higher diffusive methane fluxes to the atmosphere (up to 1.6 mmol m-2day-1). This was likely due to a faster supply of methane, but also a reduction of methane oxidation. Thus, despite the rapid adaptation and versatile genomic potential of the MOB community, seasonal water column dynamics significantly influence methane removal efficiency.
A Layered Microcircuit Model of Somatosensory Cortex with Three Interneuron Types and Cell-Type-Specific Short-Term Plasticity
Authors: Jiang Han-Jia , Qi Guanxiao , Duarte Renato , Feldmeyer Dirk , van Albada Sacha J 
Published: October 2023

AbstractThree major types of GABAergic interneurons, parvalbumin- (PV), somatostatin- (SOM) and vasoactive intestinal peptide-expressing (VIP) cells, play critical but distinct roles in the cortical microcircuitry. Their specific electrophysiology and connectivity shape their inhibitory functions. To study the network dynamics and signal processing specific to these cell types in the cerebral cortex, we developed a multi-layer model incorporating biologically realistic interneuron parameters from rodent somatosensory cortex. The model is fitted toin vivodata on cell-type-specific population firing rates. With a protocol of cell-type-specific stimulation, network responses when activating different neuron types are examined. The model reproduces the experimentally observed inhibitory effects of PV and SOM cells and disinhibitory effect of VIP cells on excitatory cells. We further create a version of the model incorporating cell-type-specific short-term synaptic plasticity (STP). While the ongoing activity with and without STP is similar, STP modulates the responses of Exc, SOM, and VIP cells to cell-type-specific stimulation, presumably by changing the dominant inhibitory pathways. With slight adjustments, the model also reproduces sensory responses of specific interneuron types recordedin vivo. Our model provides predictions on network dynamics involving cell-type-specific short-term plasticity and can serve to explore the computational roles of inhibitory interneurons in sensory functions.
Assessing Lanthanide-Dependent Methanol Dehydrogenase Activity: The Assay Matters
Authors: Phi Manh Tri , Singer Helena , Zäh Felix , Haisch Christoph , Schneider Sabine , den Camp Huub J.M. Op , Daumann Lena J. 
Published: October 2023

AbstractArtificial dye-coupled assays have been widely adopted as a rapid and convenient method to assess the activity of methanol dehydrogenases (MDH). Lanthanide(Ln)-dependent XoxF-MDHs from methanotrophs and methylotrophs are able to incorporate different lanthanides (Lns) in their active site. The artificial dye-coupled assay showed that the earlier Lns exhibit a higher enzyme activity than the late Lns. Although this assay is widely used, there are limitations. It is not unusual that a pH of 9 is required and that activators like ammonium have to be added to the assay mixture which do not reflect the conditions inside the cell. Moreover, different Ln-MDH variants are not obtained by the direct isolation from the cells grown with the respective Ln, but by metal titration of the Ln in a partial-apo-MDH or by incubation of an apo-MDH with the Ln. Herein, we report the cultivation of Ln-dependent methanotrophMethylacidiphilum fumariolicumSolV with nine different Lns, the isolation of the respective MDH and the assessment of the enzyme activity using the artificial dye-coupled assay. We compare these results with an adapted protein-coupled assay using the physiological partner and electron acceptor cytochromecGJ(cytcGJ) instead of artificial dyes. We demonstrate that, depending on the assay, two distinct trends are observed among the Ln series. The specific activity of La-, Ce- and Pr-MDH, as measured by the protein-coupled assay, exceeds the specific enzyme activity measured by the dye-coupled assay. This suggests that the early Lns also have a positive effect on the interaction between XoxF-MDH and its cytcGJthereby increasing functional efficiency.
Mapping RNA-Protein Interactions with Subcellular Resolution Using Colocalization CLIP
Authors: Yi Soon , Singh Shashi S. , Rozen-Gagnon Kathryn , Luna Joseph M. 
Published: October 2023

SummaryRNA binding proteins (RBPs) are essential for RNA metabolism and profoundly impact health and disease. The subcellular organization of RBP interaction networks with target RNAs remains largely unexplored. Here, we develop colocalization CLIP, a method that combines CrossLinking and ImmunoPrecipitation (CLIP) with proximity labeling, to explore in-depth the subcellular RNA interactions of the well-studied RNA-binding protein HuR. Using this method, we uncover HuR’s dynamic and location-specific interactions with RNA, revealing alterations in sequence preferences and interactions in the nucleus, cytosol, or stress granule compartments. We uncover HuR’s unique binding preferences within stress granules during arsenite stress, illuminating intricate interactions that conventional methodologies cannot capture. Overall, coCLIP provides a powerful method for revealing RBP:RNA interactions based on localization and lays the foundation for an advanced understanding of RBP models that incorporate subcellular location as a critical determinant of their functions.
Expression of Filaments of theGeobacterExtracellular Cytochrome OmcS inShewanella oneidensis
Authors: Lin Tong , Ding Wenqi , Zhang Danni , Yang Yun , Li Feng , Xu Dake , Lovley Derek R. , Song Hao 
Published: October 2023

ABSTRACTThe physiological role ofGeobacter sulfurreducensextracellular cytochrome filaments is a matter of debate and the development of proposed electronic device applications of cytochrome filaments awaits methods for large-scale cytochrome nanowire production. Functional studies inGeobacter sulfurreducensare stymied by the broad diversity of redox-active proteins on the outer cell surface and the redundancy and plasticity of extracellular electron transport routes.G. sulfurreducensis a poor chassis for producing cytochrome nanowires for electronics because of its slow, anaerobic growth. Here we report that filaments of theG. sulfurreducenscytochrome OmcS can be heterologously expressed inShewanella oneidensis. Multiple lines of evidence demonstrated that a strain ofS. oneidensis, expressing theG. sulfurreducensOmcS gene on a plasmid, localized OmcS on the outer cell surface. Atomic force microscopy revealed filaments with the unique morphology of OmcS filaments emanating from cells. Electron transfer to OmcS appeared to require a functional outer-membrane porin-cytochrome conduit. The results suggest thatS. oneidensis, which grows rapidly to high culture densities under aerobic conditions, may be a suitable for development of a chassis for producing cytochrome nanowires for electronics applications and may also be good model microbe for elucidating cytochrome filament function in anaerobic extracellular electron transfer.
Mutations upstream fromsdaCandmalTinEscherichia coliuncover a complex interplay between the cAMP receptor protein and different sigma factors
Authors: Frendorf Pernille Ott , Heyde Sophia A. H. , Nørholm Morten H. H. 
Published: October 2023

AbstractInEscherichia coli, one of the best understood microorganisms, much can still be learned about the basic interactions between transcription factors and promoters, particularly in the stationary phase. When a cAMP-deficientcyamutant is supplied with maltose as the main carbon source, mutations develop upstream from the two genesmalTandsdaC. Here, we explore the regulation of the two promoters, using fluorescence-based genetic reporters in combination with both spontaneously evolved and systematically engineeredcis-acting mutations. We show that in thecyamutant, regulation ofmalTandsdaCevolves toward cAMP-independence and increased expression in stationary phase. Furthermore, we show that the location of the cAMP receptor protein (Crp) binding site upstream ofmalTis important for alternative sigma factor usage. This provides new insights into the architecture of bacterial promoters and the global interplay between Crp and sigma factors in different growth phases.