bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a cytokinin-binding protein locus inMycobacterium tuberculosis
Authors: Yoo Jin Hee , Santarossa Cristina , Thomas Audrey , Ekiert Damian , Darwin K. Heran 
Published: March 2024

ABSTRACTCytokinins are adenine-based hormones that have been well-characterized in plants but are also made by bacteria, including the human-exclusive pathogenMycobacterium tuberculosis. InM. tuberculosis, cytokinins activate transcription of an operon that affects the bacterial cell envelope. In plants, cytokinins are broken down by dedicated enzymes called cytokinin oxidases into adenine and various aldehydes. In proteasome degradation-deficientM. tuberculosis, the cytokinin-producing enzyme Log accumulates, resulting in the buildup of at least one cytokinin-associated aldehyde. We therefore hypothesized thatM. tuberculosisencodes one or more cytokinin oxidases. Using a homology-based search for homologs of a plant cytokinin oxidase, we identified Rv3719 and a putative cytokinin-specific binding protein, Rv3718c. Deletion of the locus encoding these proteins did not have a measurable effect onin vitrogrowth. Nonetheless, Rv3718c bound a cytokinin with high specificity. Our data thus support a model whereby cytokinins play one or more roles in mycobacterial physiology.IMPORTANCENumerous bacterial species encode cytokinin-producing enzymes, the functions of which are almost completely unknown. This work contributes new knowledge to the cytokinin field for bacteria, and also revealed further conservation of cytokinin-associated proteins between plants and prokaryotes.
Dramatic Changes in Mitochondrial Subcellular Location and Morphology Accompany Activation of the CO2Concentrating Mechanism
Authors: Findinier Justin , Joubert Lydia-Marie , Schmid Michael F. , Malkovskiy Andrey , Chiu Wah , Burlacot Adrien , Grossman Arthur R. 
Published: March 2024

ABSTRACTDynamic changes in intracellular ultrastructure can be critical for the ability of organisms to acclimate to environmental conditions. Microalgae, which are responsible for ∼50% of global photosynthesis, compartmentalize their Rubisco into a specialized structure known as the pyrenoid when the cells experience limiting CO2conditions; this compartmentalization appears to be a component of the CO2Concentrating Mechanism (CCM), which facilitates photosynthetic CO2fixation as environmental levels of inorganic carbon (Ci) decline. Changes in the spatial distribution of mitochondria in green algae have also been observed under CO2limiting conditions, although a role for this reorganization in CCM function remains unclear. We used the green microalgaeChlamydomonas reinhardtiito monitor changes in the position and ultrastructure of mitochondrial membranes as cells transition between high CO2(HC) and Low/Very Low CO2(LC/VLC). Upon transferring cells to VLC, the mitochondria move from a central to a peripheral location, become wedged between the plasma membrane and chloroplast envelope, and mitochondrial membranes orient in parallel tubular arrays that extend from the cell’s apex to its base. We show that these ultrastructural changes require protein and RNA synthesis, occur within 90 min of shifting cells to VLC conditions, correlate with CCM induction and are regulated by the CCM master regulator CIA5. The apico-basal orientation of the mitochondrial membrane, but not the movement of the mitochondrion to the cell periphery, is dependent on microtubules and the MIRO1 protein, which is involved in membrane-microtubule interactions. Furthermore, blocking mitochondrial electron transport in VLC acclimated cells reduces the cell’s affinity for inorganic carbon. Overall, our results suggest that CIA5-dependent mitochondrial repositioning/reorientation functions in integrating cellular architecture and energetics with CCM activities and invite further exploration of how intracellular architecture can impact fitness under dynamic environmental conditions.
Genetic and phenotypic architecture of human myocardial trabeculation
Authors: McGurk Kathryn A , Qiao Mengyun , Zheng Sean L , Sau Arunashis , Henry Albert , Ribeiro Antonio Luiz P , Ribeiro Antônio H , Ng Fu Siong , Lumbers R Thomas , Bai Wenjia , Ware James S , O’Regan Declan P 
Published: March 2024

AbstractCardiac trabeculae form a network of muscular strands that line the inner surfaces of the heart. Their development depends on multiscale morphogenetic processes and, while highly conserved across vertebrate evolution, their role in the pathophysiology of the mature heart is not fully understood. We report variant associations across the allele frequency spectrum for trabecular morphology in 47,803 participants of the UK Biobank using fractal dimension analysis of cardiac imaging. We identified an association between trabeculation and rare variants in 56 genes that regulate myocardial contractility and ventricular development. Genome-wide association studies identified 68 novel loci in pathways that regulate sarcomeric function, differentiation of the conduction system, and cell fate determination. We found that trabeculation-associated variants were modifiers of cardiomyopathy phenotypes with opposing effects in hypertrophic and dilated cardiomyopathy. Together, these data provide insights into mechanisms that regulate trabecular development and plasticity, and identify a potential role in modifying monogenic disease expression.
MMA athletes demonstrate different brain vital sign profiles compared to matched controls at baseline
Authors: Munce Thayne A. , Fickling Shaun D. , Nijjer Shaquile , Poel Daniel N. , D’Arcy Ryan C.N. 
Published: March 2024

AbstractWe investigated objective brain vital signs derived from event-related potentials (ERPs) for mixed martial arts (MMA) athletes and matched controls (N=24). Brain vital sign scans were acquired from 9 MMA athletes and 15 age- and sex-matched controls. Our analysis specifically compared differences in brain vital signs between MMA athletes and controls at baseline. We predicted that MMA athletes would show significant differences relative to controls due to their ongoing exposure to repetitive head impacts. Participants were scanned to extract three well-established ERPs: N100 for auditory sensation; P300 for basic attention; and N400 for cognitive processing. Scans were verified using automated reports, with N100, P300, and N400 amplitudes and latencies manually identified by a blinded reviewer. Groups were evaluated at the waveform level with a mass-univariate analysis using non-parametric resampling. Brain vital signs were compared across groups with a Kruskal-Wallis H-test for independent samples, with FDR correction for multiple comparisons. We identified significant differences between MMA athletes and controls. Specifically, there were significant N400 amplitude reductions, indicating that exposure to repetitive head impacts in MMA may be associated with changes in brain function.
Ultrasonic Texture Analysis for Acute Myocardial Infarction Risk Stratification: A Pilot Study
Authors: Hathaway Quincy A. , Jamthikar Ankush D. , Chaitman Bernard R. , Carson Jeffery , Yanamala Naveena , Sengupta Partho P. 
Published: March 2024

AbstractBackgroundCurrent risk stratification tools for acute myocardial infarction (AMI) have limitations, particularly in predicting mortality. This study utilizes cardiac ultrasound radiomics (i.e., ultrasomics) to risk stratify AMI patients when predicting all-cause mortality.MethodsThe study included 197 patients: a) retrospective internal cohort (n=155) of non-ST-elevation myocardial infarction (n=63) and ST-elevation myocardial infarction (n=92) patients, and b) external cohort from the multicenter Door-To-Unload in ST-segment–elevation myocardial infarction [DTU-STEMI] Pilot Trial (n=42). Echocardiography images of apical 2, 3, and 4-chamber were processed through an automated deep-learning pipeline to extract ultrasomic features. Unsupervised machine learning (topological data analysis) generated AMI clusters followed by a supervised classifier to generate individual predicted probabilities. Validation included assessing the incremental value of predicted probabilities over the Global Registry of Acute Coronary Events (GRACE) risk score 2.0 to predict 1-year all-cause mortality in the internal cohort and infarct size in the external cohort.ResultsThree phenogroups were identified: Cluster A (high-risk), Cluster B (intermediate-risk), and Cluster C (low-risk). Cluster A patients had decreased LV ejection fraction (P=0.004) and global longitudinal strain (P=0.027) and increased mortality at 1-year (log rank P=0.049). Ultrasomics features alone (C-Index: 0.74 vs. 0.70, P=0.039) and combined with global longitudinal strain (C-Index: 0.81 vs. 0.70, P<0.001) increased prediction of mortality beyond the GRACE 2.0 score. In the DTU-STEMI clinical trial, Cluster A was associated with larger infarcts size (>10% LV mass, P=0.003), compared to remaining clusters.ConclusionsUltrasomics-based phenogroup clustering, augmented by TDA and supervised machine learning, provides a novel approach for AMI risk stratification.
A protocol for a scoping review on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies
Authors: Essouma Mickael , de Araujo Daniel Brito , Day Jessica , Gupta Latika , Knight Adina Kay , Reed Ann , Naddaf Elie , Elias Sallum Adriana Maluf , Marrani Edoardo , Conticini Edoardo , Appenzeller Simone , Knight Adina Kay , Dimachkie Mazen , Abou Tamima Mohamad , Gibson Daren , Kirkhus Eva , van der Koi Anneke J , Lilleker James B , Lucchini Matteo , Machado Pedro , Riopel Mary Anne , Sanner Helga , Schiffenbauer Adam , Guimarães Julio Brandão , Saad-Magalhaes Claudia , O’Hanlon Susan , Omori Clarissa Harumi , Phaneuf Susan , Sanner Helga , Moghadam-Kia Siamak , Tolend Mirkamal , Ventura Iazsmin Bauer , Rider Lisa G , Christopher-Stine Lisa , Paik Julie J , Feldman Brian , Shinjo Samuel Katsuyuki , Doria Andrea Schwarz 
Published: March 2024

ABSTRACTBackgroundCurrently, there is lack of standardization of magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults among treatment centres across the globe. Therefore, we will perform scoping reviews of the literature to inform available semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs with the final goal of providing evidence-based information for the future development of a universal standardized MRI scoring system in specific research and clinical settings in this population.MethodsElectronic databases (PubMed, EMBASE, and Cochrane) will be searched to select relevant articles published from January 2000 to October 2023. Data will be synthesized narratively.DiscussionThis scoping review will extensively map evidence on the indications, utility for diagnosis and assessment of disease activity and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for MRI assessment of skeletal muscle changes in patients with IIMs.
An efficient inducible model for the control of gene expression in renin cells
Authors: Medrano Silvia , Yamaguchi Manako , Yamaguchi Hiroki , de Almeida Lucas Ferreira , Sigmund Curt D. , Sequeira-Lopez Maria Luisa S. , Ariel Gomez R. 
Published: March 2024

ABSTRACTBackgroundFate mapping and genetic manipulation of renin cells have relied on either non-inducibleCrelines that can introduce developmental effects of gene deletion or BAC transgene-based inducible models that may be prone to spurious and/or ectopic gene expression.MethodsWe generated an inducible mouse model in whichCreERT2is under the control of the endogenousAkr1b7gene, an independent marker of renin cells.ResultsWe evaluated the pattern ofCreexpression inAkr1b7CreERT2/+;R26RmTmG/+mice in which Akr1b7+/renin+cells become GFP+ upon tamoxifen administration. At E18.5 and P5, GFP was found in Juxtaglomerular cells, along the arterioles, and in the glomerular mesangium. In adult kidneys, GFP was present mainly in Juxtaglomerular cells. In mice treated with captopril and a low sodium diet to induce recruitment of renin cells, GFP extended along the afferent arterioles and in the mesangium. In addition, we deleted renin in adult mice and found a marked reduction in kidney renin expression and mean arterial pressure in mutant animals. When subjected to a homeostatic threat, mutant mice were unable to recruit renin+cells. Most importantly, mice with renin deletion induced in the adult developed concentric vascular hypertrophy ruling out potential developmental effects on the vasculature due to the lack of renin.ConclusionsRenin can be efficiently and specifically deleted in renin cells in adult life using our conditional model.Akr1b7CreERT2mice constitute an excellent model for the fate mapping of renin cells and for the spatial and temporal control of gene expression in renin cells.
MAC3A and MAC3B modulateFLMsplicing to repress photoperiod-dependent floral transition
Authors: Huang Yu-Wen , Tseng Chih-Yen , Tu Yi-Tsung , Hsieh Hsin-Yu , Wang Yu-Sen , Ly Yun-Tung , Chen Yu-Zhen , Tu Shih-Long , Lee Chin-Mei 
Published: March 2024

AbstractPlants adjust their flowering time by integrating environmental cues through complex regulatory networks. RNA splicing plays a crucial role in modulating gene expression in response to flowering signals. The MOS4-associated complex (MAC), consisting of the evolutionarily conserved E3 ubiquitin ligases MAC3A and MAC3B, is pivotal in splicing regulation. However, their involvement in floral transition remained unclear. This study observed thatmac3a/mac3bmutants flowered significantly earlier under short-day (SD) conditions, a phenotype absent under long-day (LD) conditions. This early flowering correlated with upregulation ofFLOWERING LOCUS T(FT) andSUPPRESSOR OF OVEREXPRESSION OF CO 1(SOC1) compared to wild-type plants. Transcriptomic analysis revealed alterations in transcript levels and splicing profiles of key floral regulators across different flowering pathways. Further investigation identified the thermosensory flowering regulatorFLOWERING LOCUS M(FLM) as being influenced byMAC3AandMAC3B. Subsequently, we found thatMAC3AandMAC3Bexhibited higher expression and were associated withFLMtranscripts to modulate their splicing in SD. This study elucidates how the MAC complex, through RNA splicing regulation, integrates environmental signals to modulate flowering, unveiling a new layer of complexity in flowering pathways crosstalk under non-inductive photoperiods.
Ligand-induced CaMKIIα hub Trp403 flip, hub domain stacking and kinase inhibition
Authors: Narayanan Dilip , Larsen Anne Sofie G. , Gauger Stine Juul , Adafia Ruth , Hammershøi Rikke Bartschick , Hamborg Louise , Bruus-Jensen Jesper , Griem-Krey Nane , Gee Christine L. , Frølund Bente , Stratton Margaret M. , Kuriyan John , Kastrup Jette Sandholm , Langkilde Annette E. , Wellendorph Petrine , Solbak Sara M. Ø. 
Published: March 2024

Abstractγ-Hydroxybutyric acid (GHB) analogs are small molecules that bind competitively to a specific cavity in the oligomeric CaMKIIα hub domain. Binding affects conformation and stability of the hub domain, which may explain the neuroprotective action of some of these compounds. Here, we describe molecular details of interaction of the larger-type GHB analog 2-(6-(4-chlorophenyl)imidazo[1,2-b]pyridazine-2-yl)acetic acid (PIPA). Like smaller-type analogs, PIPA binding to the CaMKIIα hub domain promoted thermal stability. PIPA additionally inhibited CaMKIIα kinase activity by reducing CaM sensitivity. A high-resolution X-ray crystal structure of a stabilized CaMKIIα (6x mutant) hub construct revealed details of the binding mode of PIPA, which involved outward placement of tryptophan 403 (Trp403), a central residue in a flexible loop close to the upper hub cavity. Small-angle X-ray scattering (SAXS) solution structures and mass photometry of the CaMKIIα wildtype hub domain in the presence of PIPA revealed a high degree of ordered self-association (stacks of CaMKIIα hub domains). This stacking neither occurred with the smaller compound 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA), nor when Trp403 was replaced with leucine (W403L). Additionally, CaMKIIα W403L hub was stabilized to a larger extent by PIPA compared to CaMKIIα hub wildtype, indicating that loop flexibility is important for holoenzyme stability. Thus, we propose that ligand-induced outward placement of Trp403 by PIPA, which promotes an unforeseen mechanism of hub domain stacking, may be involved in the observed reduction in CaMKIIα kinase activity. Altogether, this sheds new light on allosteric regulation of CaMKIIα activity via the hub domain.
The expression of integron arrays is shaped by the translation rate of cassettes
Authors: Carvalho André , Hipólito Alberto , da Roza Filipa Trigo , García-Pastor Lucía , Vergara Ester , Buendía Aranzazu , García-Seco Teresa , Escudero José Antonio 
Published: March 2024

ABSTRACTIntegrons are key elements in the rise and spread of multidrug resistance in Gram-negative bacteria. These genetic platforms capture cassettes containing promoterless genes and stockpile them in arrays of variable length. In the current integron model, expression of cassettes is granted by the Pc promoter in the platform and is assumed to decrease as a function of its distance. Here we explored this model using a large collection of 136 antibiotic resistance cassettes and show that the effect of distance is in fact negligible. Instead, cassettes have a strong impact in the expression of downstream genes because their translation rate affects the stability of the whole polycistronic mRNA molecule. Hence, poorly translated cassettes decrease the expression and resistance phenotype of cassettes downstream. Our data puts forward a novel integron model in which expression is contingent on the translation of cassettes upstream, rather than on the distance to the Pc.
Genomic diversity inPaenibacillus polymyxa: Unveiling distinct species groups and functional variability
Authors: Wallner Adrian , Antonielli Livio , Mesguida Ouiza , Rey Patrice , Compant Stéphane 
Published: March 2024

AbstractPaenibacillus polymyxais a bacterial species of high interest, as suggested by the increased number of publications on its functions in the past years. Accordingly, the number of described strains and sequenced genomes is also on the rise. While functional diversity was repeatedly suggested for this species, the available genomic data is now sufficient to confidently segregate strains affiliated toP. polymyxainto two major species groups. As these strains exhibit considerable potential in agriculture, medicine, and bioremediation, it is preferable to clarify their taxonomic affiliation to facilitate reliable and durable approval as active ingredients. Strains currently affiliated toP. polymyxacan be separated into two major species groups with differential potential in nitrogen fixation, plant interaction, secondary metabolism, and antimicrobial resistance, as inferred from genomic data.
Isolation and characterization of a phage collection againstPseudomonas putida
Authors: Brauer Age , Rosendahl Sirli , Kängsep Anu , Lewańczyk Alicja Cecylia , Rikberg Roger , Hõrak Rita , Tamman Hedvig 
Published: March 2024

AbstractThe environmental bacteriumPseudomonas putidahas a wide range of metabolic pathways and thus entails great promise both as cell factories in biotechnological production and for bioremediation approaches to degrade various aromatic pollutants. To thrive in the environment,P. putidahas to be able to endure the constant threat posed by bacteriophages. Surprisingly, up until now, only a few phages have been isolated for the common laboratory strainP. putidaKT2440, and no phage defence mechanisms have been characterized yet. Here, we introduce a novelCollection ofEnvironmentalPseudomonas putidaPhages fromEstonia (CEPEST), consisting of 67 dsDNA phages that belong to 22 phage species and nine phage genera. We show that most of the phages in the CEPEST collection are more infectious at lower temperatures, have a narrow host range, and require intact LPS forP. putidainfection. Additionally, we demonstrate that cryptic prophages in theP. putidachromosome strongly protect against the infection of many phages, whereas the chromosomal toxin-antitoxin systems play no role in phage defence ofP. putida.
Microbiome turnover during offspring development varies with maternal care, but not moult, in a hemimetabolous insect
Authors: Cheutin Marie-Charlotte , Boucicot Manon , Meunier Joël 
Published: March 2024

AbstractThe ecological success of insects often depends on their association with beneficial microbes. However, insect development involves repeated moults, which can have dramatic effects on their microbial communities. Here, we investigated whether and how moulting affects the microbiome of a hemimetabolous insect, and whether maternal care can modulate these effects. We reared European earwig juveniles with or without mothers and used 16S rRNA metabarcoding to analyse the prokaryotic fraction of the core microbiome of eggs, recently and old moulted individuals at four developmental stages and the resulting adults. The 218 samples obtained showed that the microbiome diversity changed non-linearly during development and that these changes were associated with bacterial biomarkers. Surprisingly, these changes did not occur during moulting, but rather between the beginning and end of certain developmental stages. We also found that access to maternal care affected the microbiome of both juveniles and adults, even when the last contact with mothers was two months before adulthood. Overall, these results provide new insights into our understanding of the (in)stability of the prokaryotic microbiome in hemimetabolous insects and its independence from moult. More generally, they question the role of microbiome acquisition through maternal care in maintaining family life in species where this behaviour is facultative.
Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST
Authors: Kraus Felix , He Yuchen , Swarup Sharan , Overmyer Katherine A. , Jiang Yizhi , Brenner Johann , Capitanio Cristina , Bieber Anna , Jen Annie , Nightingale Nicole M. , Anderson Benton J. , Lee Chan , Paulo Joao A. , Smith Ian R. , Plitzko Jürgen M. , Gygi Steven P. , Schulman Brenda A. , Wilfling Florian , Coon Joshua J. , Harper J. Wade 
Published: March 2024

SUMMARYLysosomal storage diseases (LSDs) comprise ∼50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multi-omic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially inNPC1-/-andNPC2-/-mutants, where lysosomes accumulate cholesterol. Autophagic and endocytic cargo delivery failures correlated with elevated lyso-phosphatidylcholine species and multi-lamellar structures visualized by cryo-electron tomography. Loss of mitochondrial cristae, MICOS- complex components, and OXPHOS components rich in iron-sulfur cluster proteins inNPC2-/-cells was largely alleviated when iron was provided through the transferrin system. This study reveals how lysosomal dysfunction affects mitochondrial homeostasis and underscores nMOST as a valuable discovery tool for identifying molecular phenotypes across LSDs.