bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETTIN-mediated auxin signalling is an angiosperm-specific neofunctionalization for carpel development
Authors: Ang Aaron Chun Hou , Mutte Sumanth , Weijers Dolf , Østergaard Lars 
Published: September 2024

SUMMARYThe phytohormone auxin affects processes throughout plant growth and development. While auxin signalling has been mainly attributed to a repressor degradation-based pathway, numerous alternative mechanisms for how auxin mediates its effect have been revealed in recent years. One such mechanism involves a direct auxin-induced switch in the transcriptional regulatory activity of the Auxin Response Factor (ARF) ETTIN (ETT). ETT lacks a conserved C-terminus domain involved in canonical pathway interactions but contains a middle region domain mediating auxin binding. As the ETT clade only exists in the angiosperms, it remains unknown when the pathway evolved. Here we provide evidence for a two-step origin of the ETT clade and its neofunctionalisation through the gain of auxin perception in gynoecium patterning. Phylogenetic analyses reveal the structural divergence of ETT and its paralogue ARF4 after their duplication from an ancestral euphyllophyte ARF3/4 clade. Auxin sensitivity was identified as an ETT-specific innovation that likely originated in the last common angiosperm ancestor. Furthermore,in plantacomplementation experiments demonstrated the full genetic redundancy of ETT and ARF4 in leaf and ovary development, but a specialised role for the ETT-mediated auxin signalling pathway in style development. Our work thus provides evidence that ETT was recruited from an ancestral role in leaf development and subsequently underwent neofunctionalisation through the acquisition of direct auxin sensing for a novel role in gynoecium patterning.
The speed limits for tau pathology progression in Alzheimer’s disease
Authors: Hoenig Merle C. , Dzialas Verena , Doering Elena , Bischof Gérard N. , van Eimeren Thilo , Drzezga Alexander ,   Alzheimer’s Disease Neuroimaging Initiative
Published: September 2024

AbstractObjectiveTo examine interactive effects of modifiable factors, genetic determinants and load-dependent pathology effects on tau pathology progression.MethodsData of 162 amyloid-positive individuals were included, for whom longitudinal [18F]AV-1451-PET scans, baseline information on global amyloid load, ApoE4 status, body-mass-index (BMI), hypertension, education, neuropsychiatric symptom severity and demographic information were available in ADNI. All [18F]AV-1451 PETs were intensity-standardized (reference: inferior cerebellum), z-transformed (control sample: 147 amyloid-negative subjects) and subsequently thresholded (z-score > 1.96) and converted to volume-maps. Based on these volume-maps, tau-changes over time were assessed in terms of 1)tau-speed(i.e. newly affected volume at follow-up), and 2)tau-level-rise(i.e. tau increase in previously affected volume). These two measures were entered as dependent variables in separate linear mixed effects models including four baseline risk factors (BMI, education, hypertension, neuropsychiatric symptom severity), baseline amyloid, tau-volume or tau burden, ApoE4 status, clinical stage, sex, and age as predictors. Next, we tested the interactive effects between baseline amyloid or tau burden with the four modifiable factors on either tau-speed or tau-level-rise, respectively.ResultsFaster tau-speed was linked to higher BMI, female sex, ApoE4-status, and baseline tau-volume. The effect of baseline tau-volume on tau-speed was driven by greater global amyloid burden. In terms of tau-level-rise, we observed that lower hypertension and BMI were linked to a slower increase in tau burden. A load-dependent effect of baseline amyloid and tau burden was found. Higher amyloid and BMI as well as lower education and higher tau burden were linked to greater tau-level-rise.ConclusionEducation, BMI and hypertension differentially influence tau speed and level rise by its interaction with initial pathological burden. Timely modification of these factors may overall slow tau’s progression.
Biases in volumetric versus surface analyses in population receptive field mapping
Authors: Linhardt David , Woletz Michael , Paz-Alonso Pedro M. , Windischberger Christian , Lerma-Usabiaga Garikoitz 
Published: September 2024

AbstractPopulation receptive field (pRF) mapping is a quantitative fMRI analysis method that links visual field positions with specific locations in the visual cortex. A common preprocessing step in pRF analyses involves projecting volumetric fMRI data onto the cortical surface, often leading to upsampling of the data. This process may introduce biases in the resulting pRF parameters. To investigate this, we present CON-pRF, a fully containerized pipeline for pRF mapping analysis that is designed to maximize reproducibility in pRF mapping studies. Using this pipeline, we compared pRF maps generated from original volumetric with those from upsampled surface data. Our results show substantial increases in pRF coverage in the central visual field of upsampled data sets. These effects were consistent across early visual cortex areas V1-3. Further analysis indicates that this bias is primarily driven by the non-linear relationship between cortical distance and visual field eccentricity, known as cortical magnification. Our results demonstrate that reproducible analysis pipelines enable the detection of potential biases introduced by varying processing steps, particularly when comparing across differently processed datasets.Key PointsSpatial upsampling increases pRF coverage in the fovea due to enhanced CNR and cortical magnification.The study highlights the need for careful consideration of data processing steps.CON-pRF is a containerized pipeline for enhanced reproducibility in pRF analysis.
Early Fibrin Biofilm Development in Cardiovascular Infections
Authors: Oukrich Safae , Hong Jane , Leon-Grooters Mariël , van Cappellen Wiggert , Slotman Johan A. , Koenderink Gijsje H. , van Wamel Willem J.B. , de Maat Moniek P.M. , Kooiman Klazina , Lattwein Kirby R. 
Published: September 2024

AbstractThe single most common microbe causing cardiovascular infections isStaphylococcus aureus(S. aureus).S. aureusproduces coagulase that converts fibrinogen to fibrin, which is incorporated into biofilms. This process aids in adherence to intravascular structures, defense against the host immune system, and resistance to antimicrobial treatment. Despite its significance, fibrin formation inS. aureusbiofilms remains poorly understood. Therefore, this study aimed to elucidate the early development of cardiovascular biofilms. Clinically isolated coagulase-positiveS. aureusand coagulase-negativeStreptococcus gordonii(S. gordonii) from patients with cardiovascular infections, and a coagulase mutantS. aureusΔcoa, were grown in tryptic soy broth (TSB), Iscove’s Modified Dulbecco’s Medium (IMDM), and pooled human plasma, with or without porcine heart valves. Bacterial growth, metabolic activity, and bacterial fibrinogen utilization were measured over 24 hr at 37 °C. Time-lapse confocal microscopy was used to visualize and track biofilm development.S. aureusexhibited more growth in TSB and human plasma thanS. gordoniiandS. aureusΔcoa, but showed similar growth asS. aureusΔcoa in IMDM. Peak metabolic activity for all isolates was highest in TSB and lowest in human plasma. The presence of porcine valves caused strain-dependent alterations in time to peak metabolic activity. Confocal imaging revealed fibrin-based biofilm development exclusively in the coagulase-producingS. aureusstrains. Between 2 and 6 hr of biofilm development, 74.9% (p=0.034) of the fibrinogen from the medium was converted to fibrin. Variations in fibrin network porosity and density were observed among different coagulase-producingS. aureusstrains. Fibrin formation is mediated byS. aureuscoagulase and first strands occurred within 3 hr for clinical strains after exposure to human plasma. This study stresses the importance of experimental design given the bacterial changes due to different media and substrates and provides insights into the early pathogenesis ofS. aureuscardiovascular biofilms.HighlightsBacterial growth and activity are medium and substrate dependentCoagulase is necessary forStaphylococcus aureusfibrin biofilm developmentFibrin strands begin forming inStaphylococcus aureusbiofilms within 3 hours
A newBetaflexivirusspecies inFerraria crispaplants
Authors: Dekker Rob J. , de Leeuw Wim C. , van Olst Marina , Ensink Wim A. , van Leeuwen Selina , Breit Timo M. , Jonker Martijs J. 
Published: September 2024

AbstractThe global virome is still largely unknown. In this study we describe the discovery of a newBetaflexivirusspecies inFerraria crispaplants. The plant samples were collected in an experiment of 25Asparagalesplants, obtained from an urban botanic garden in the Netherlands, and analyzed by smallRNA-seq as well as RNA-seq. The newBetaflexivirusonly occurred in fourFerraria cripsaplants and was tentatively named Ferraria Betaflexivirus 1 (FerBfV-1). ThisBetaflexivirusshowed an RNA genome structure characteristic for the genusCapillovirus, a single-stranded (+) RNA virus. The closest knownCapillovirusesin GenBank showed a protein similarity less than 49%, which is well below the proposed demarcation value of species in this genus. Further comparison analysis of theCapillovirusgenus revealed the possible presence of two groups.
Mitochondrial Deletions and Healthspan: Lessons from the Common Repeat
Authors: Shamanskiy Victor , Gunbin Konstantin , Tretiakov Evgenii O. , Mazunin Ilya , Skripskaya Viktoria , Mikhailova Alina A. , Mikhailova Alina G. , Ree Natalia , Timonina Valeriia , Knorre Dmitry , Kunz Wolfram S. , Fiorellino Nathan , Reymond Alexandre , Bazykin Georgii A. , Fellay Jacques , Tanaka Masashi , Khrapko Konstantin , Popadin Konstantin 
Published: September 2024

AbstractAging, characterized by a series of functional declines correlated with advancing chronological age, has a significant mitochondrial DNA (mtDNA) component, with somatic mtDNA deletions playing a central role. In post-mitotic or slow-dividing cells like neurons and skeletal muscles, selfish mtDNA deletions clonally expand within a cell, ultimately leading to the deterioration and death of host cells and appearence of age-related phenotypes. Thus reducing the burden of somatic deletions could have far- reaching systemic benefits for the entire human body. Given the crucial role of direct nucleotide repeats in the formation of mitochondrial deletions, we hypothesize that minimizing these repeats in the human mitochondrial genome could enhance healthspan by decreasing somatic deletions. To investigate this hypothesis, we focus on the “common repeat”, a 13-base pair perfect direct repeat sequence (ACCTCCCTCACCA) located at positions 8470-8482 and 13447-13459, respectively. This perfect repeat: (i) is highly prevalent, with its potential deleterious consequences affecting the majority of humans; (ii) represents one of the most fragile sites, highly prone to forming deletions; (iii) when disrupted, is associated with a decreased somatic deletion load and enhanced human healthspan; (iv) is likely to experience positive selection in the present or near future due to indirect fitness effects, such as the “grandmother effect”, and direct fitness effects, such as (v) a decreased mutation rate. These observations support the argument that reducing the mtDNA somatic deletion load through targeted disruption of these repeats, or by using naturally occurring polymorphisms with disrupted repeats in mitochondrial medicine, could be an effective approach to increasing human longevity.
Aneuploidy of Specific Chromosomes is Beneficial to Cells Lacking Spindle Checkpoint Protein Bub3
Authors: Gadgil Pallavi , Ballew Olivia , Sullivan Timothy J. , Lacefield Soni 
Published: September 2024

ABSTRACTAneuploidy typically poses challenges for cell survival and growth. However, recent studies have identified exceptions where aneuploidy is beneficial for cells with mutations in certain regulatory genes. Our research reveals that cells lacking the spindle checkpoint geneBUB3exhibit aneuploidy of select chromosomes. While the spindle checkpoint is not essential in budding yeast, the loss ofBUB3andBUB1increases the probability of chromosome missegregation compared to wildtype cells. Contrary to the prevailing assumption that the aneuploid cells would be outcompeted due to growth defects, our findings demonstrate thatbub3Δ cells consistently maintained aneuploidy of specific chromosomes over many generations. We investigated whether the persistence of these additional chromosomes inbub3Δ cells resulted from the beneficial elevated expression of certain genes, or mere tolerance. We identified several genes involved in chromosome segregation and cell cycle regulation that confer an advantage to Bub3-depleted cells. Overall, our results suggest that the upregulation of specific genes through aneuploidy may provide a survival and growth advantage to strains with poor chromosome segregation fidelity.AUTHOR SUMMARYAccurate chromosome segregation is crucial for the proper development of all living organisms. Errors in chromosome segregation can lead to aneuploidy, characterized by an abnormal number of chromosomes, which generally impairs cell survival and growth. However, under certain stress conditions, such as in various cancers, cells with specific mutations and extra copies of advantageous chromosomes exhibit improved survival and proliferation. In our study, we discovered that cells lacking the spindle checkpoint protein Bub3 became aneuploid, retaining specific chromosomes. This finding was unexpected because althoughbub3Δ cells have a higher rate of chromosome mis-segregation, they were not thought to maintain an aneuploid karyotype. We investigated whether the increased copy number of specific genes on these acquired chromosomes offered a benefit to Bub3-deficient cells. Our results revealed that several genes involved in chromosome segregation and cell cycle regulation prevented the gain of chromosomes upon Bub3-depletion, suggesting that these genes confer a survival advantage. Overall, our study demonstrates that cells lacking Bub3 selectively retain specific chromosomes to increase the copy number of genes that promote proper chromosome segregation.
The contributions of biological maturity and experience to fine motor development in adolescence
Authors: Berencsi Andrea , Gombos Ferenc , Fehér Lili Julia , Gerván Patrícia , Utczás Katinka , Oláh Gyöngyi , Tróznai Zsófia , Kovács Ilona 
Published: September 2024

AbstractFine motor function develops into adulthood, but little is known about the differential effects of biological maturation and experience on speed and complex sequential performance of the hand. To determine maturity levels, ultrasonic bone age (BA) was assessed in 225 adolescents (123 females; BA range: 9.9 to 17.9 years). The role of experience was evaluated based on chronological age (CA, range: 11.1 to 16.5 years), musical instrumental experience, and handedness. Multiple linear regression modeling showed that BA is the strongest predictor of sequential motor performance, while CA influenced motor speed when no musical instrumental experience was present. When present, the amount of highly specific musical instrumental experience becomes the main predictor of sequential performance.
Design of linked-domain protein inhibitors of UBE2D as tools to study cellular ubiquitination
Authors: Bukhari Zara , Gu Li , Nederstigt Anneroos E. , Cope Logan J. , Bolhuis Derek L. , Harvey Kim , Allen Tristan , Hill Spencer , Yang Yujie , Lawson Guy , Lu Cai , Tran Tommy , Pineda Leah , Low Leanne , Chiang Andrew , Song Jason , Fong Michelle V. , Rangel Vanessa M. , Chan William K. , Kleiger Gary , Goldfarb Dennis , Vierra Craig A. , Brown Nicholas G. , Harrison Joseph S. 
Published: September 2024

ABSTRACTUbiquitin (Ub) is a post-translational modification that largely controls proteostasis through mechanisms spanning transcription, translation, and notably, protein degradation. Ub conjugation occurs through a hierarchical cascade of three enzyme classes (E1, E2, and E3s) involving >1000 proteins that regulate the ubiquitination of proteins. The E2 Ub-conjugating enzymes are the midpoint, yet their cellular roles remain under-characterized, partly due to a lack of inhibitors. For example, the cellular roles of the promiscuous E2 UBE2D/UBCH5 are not well described. Here, we develop a highly selective, multivalent, engineered protein inhibitor for the UBE2D family that simultaneously targets the RING- and backside-binding sites. In HeLa cells, these inhibitors phenocopy knockdown of UBE2D by reducing the IC50to cisplatin and whole-cell proteomics reveal an increased abundance of ∼20% of the identified proteins, consistent with reduced Ub degradation and proteotoxic stress. These precision tools will enable new studies probing UBE2D’s central role in proteome management.
Sex-dependent metabolic remodeling of kidneys revealed by arteriovenous metabolomics
Authors: Kelly Miranda E. , Hoffner Lauren A. , Ramirez Cuauhtemoc B. , Anica Alexis L. , Kim Joohwan , Tong Gregory , Kim Yeojin , Choi Wonsuk , Jang Kihong , Alam Yasmine H. , Jung Sunhee , Le Johnny , Tamburini Ian , Lopez Miranda L. , Bae Hosung , Chun Yujin , Song Won-Suk , Martinez Thomas F. , Jang Cholsoon , Lee Gina 
Published: September 2024

AbstractSex is a fundamental biological variable important in biomedical research, drug development, clinical trials, and prevention approaches. Among many organs, kidneys are known to exhibit remarkable structural, histological, and pathological differences between sexes. However, whether and how kidneys display distinct metabolic activities between sexes is poorly understood. By developing kidney-specific arteriovenous (AV) metabolomics combined with transcriptomics, we report striking sex differences in both basal metabolic activities and adaptive metabolic remodeling of kidneys after a fat-enriched ketogenic diet (KD), a regimen known to mitigate kidney diseases and improve immunotherapy for renal cancer. At the basal state, female kidneys show highly accumulated aldosterone and various acylcarnitines. In response to the KD, aldosterone levels remain high selectively in females but the sex difference in acylcarnitines disappears. AV data revealed that, under KD, female kidneys avidly take up circulating fatty acids and release 3-hydroxybutyrate (3-HB) whereas male kidneys barely absorb fatty acids but consistently take up 3-HB. Although both male and female kidneys take up gluconeogenic substrates such as glycerol, glutamine and lactate, only female kidneys exhibit net glucose release. Kidney transcriptomics data incompletely predict these sex differences, suggesting post-transcriptional/translational regulation mechanisms. This study provides foundational insights into the sex-dependent and diet-elicited metabolic flexibility of the kidneys in vivo, serving as a unique resource for understanding variable disease prevalence and drug responses between male and female kidneys.
Genetic variation in phenology of wildArabidopsis thalianaplants
Authors: DeLeo Victoria L. , Des Marais David L. , Juenger Thomas E. , Lasky Jesse R. 
Published: September 2024

AbstractPhenology and the timing of development are often under selection, but at the same time influence selection on other traits by controlling how traits are expressed across seasons. Plants often exhibit high natural genetic variation in phenology when grown in controlled environments, and many genetic and molecular mechanisms underlying phenology have been dissected. There remains considerable diversity of germination and flowering time within populations in the wild and the contribution of genetics to phenological variation of wild plants is largely unknown. We obtained collection dates of naturally inbredArabidopsis thalianaaccessions from nature and compared them to experimental data on the descendant inbred lines that we synthesized from two new and 155 published controlled experiments. We tested whether the genetic variation in flowering and germination timing from experiments predicted the phenology of the same inbred lines in nature. We found that genetic variation in phenology from controlled experiments significantly, but weakly, predicts day of collection from the wild, even when measuring collection date with accumulated photothermal units. We found that experimental flowering time breeding values were correlated to wild flowering time at location of origin estimated from herbarium collections. However, local variation in collection dates within a region was not explained by genetic variation in experiments, suggesting high plasticity across small-scale environmental gradients. This apparent low heritability in natural populations may suggest strong selection or many generations are required for phenological adaptation and the emergence of genetic clines in phenology.
Suppression by RNA Polymerase I Inhibitors Varies Greatly Between Distinct RNA Polymerase I Transcribed Genes in Malaria Parasites
Authors: Samuel Hermela , Campelo-Morillo Riward , Kafsack Björn F.C. 
Published: September 2024

AbstractTranscription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is the rate-limiting step in ribosome biogenesis and a major determinant of cellular growth rates. Unlike virtually every other eukaryote, which express identical rRNA from large tandem arrays of dozens to hundreds of identical rRNA genes in every cell, the genome of the human malaria parasitePlasmodium falciparumcontains only a handful single-copy 47S rRNA loci that differ substantially from one another in length, sequence and expression in different cell-types. We found that growth of malaria parasite was acutely sensitive to the Pol I inhibitors 9-hydroxyellipticine and BMH-21 and demonstrate that they greatly reduce the transcription of 47S rRNAs as well as transcription of other non-coding RNA genes. Surprisingly, we found that the various types of Pol I-transcribed genes differed by more than two orders of magnitude in their susceptibility to these inhibitors and explore the implications of these findings for regulation of rRNA inP. falciparum.