bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem cell homeostasis in the root ofArabidopsisinvolves cell type specific complex formation of key transcription factors
Authors: Strotmann Vivien I. , García-Gómez Monica L. , Stahl Yvonne 
Published: April 2024

AbstractInArabidopsis thaliana, the stem cell niche (SCN) within the root apical meristem (RAM) is maintained by an intricate regulatory network that ensures optimal growth and high developmental plasticity. Yet, many aspects of this regulatory network of stem cell quiescence and replenishment are still not fully understood. Here, we investigate the interplay of the key transcription factors (TFs) BRASSINOSTEROID AT VASCULAR AND ORGANIZING CENTRE (BRAVO), PLETHORA 3 (PLT3) and WUSCHEL-RELATED HOMEOBOX 5 (WOX5) involved in SCN maintenance. Phenotypical analysis of mutants involving these TFs uncover their combinatorial regulation of cell fates and divisions in the SCN. Moreover, interaction studies employing fluorescence resonance energy transfer fluorescence lifetime imaging microscopy (FRET-FLIM) in combination with novel analysis methods, allowed us to quantify protein-protein interaction (PPI) affinities as well as higher-order complex formation of these TFs. We integrated our experimental results into a computational model, suggesting that cell type specific profiles of protein complexes and characteristic complex formation, that is also dependent on prion-like domains in PLT3, contribute to the intricate regulation of the SCN. We propose that these unique protein complex ‘signatures’ could serve as a read-out for cell specificity thereby adding another layer to the sophisticated regulatory network that balances stem cell maintenance and replenishment in theArabidopsisroot.
Similarity of drug targets to human microbiome metaproteome promotes pharmacological promiscuity
Authors: Beaudoin Christopher A. , Norget Shannon , Hala Sharif , van Tonder Andries J. 
Published: April 2024

AbstractSimilarity between candidate drug targets and human proteins is commonly assessed to minimize the occurrence of side effects. Although numerous drugs have been found to disrupt the health of the human microbiome, no comprehensive comparison between established drug targets and the human microbiome metaproteome has yet been conducted. Therefore, herein, sequence and structure alignments between human and pathogen drug targets and representative human gut, oral, and vaginal microbiome metaproteomes were performed. Both human and pathogen drug targets were found to be similar in sequence, function, structure, and drug binding capacity to proteins in diverse pathogenic and non-pathogenic bacteria from all three microbiomes. The gut metaproteome was identified as particularly susceptible overall to off-target effects. Certain symptoms, such as infections and immune disorders, may be more common among drugs that non-selectively target host microbiota. These findings suggest that similarities between human microbiome metaproteomes and drug target candidates should be routinely checked.
Interplay between a polerovirus and a closterovirus decreases aphid transmission of the polerovirus
Authors: Khechmar Souheyla , Chesnais Quentin , Villeroy Claire , Brault Véronique , Drucker Martin 
Published: April 2024

ABSTRACTMulti-infection of plant by viruses is very common and can change drastically infection parameters such as virus accumulation, distribution and vector transmission. Sugar beet is an important crop that is frequently co-infected by the polerovirus beet chlorosis virus (BChV) and the closterovirus beet yellows virus (BYV), both vectored by the green peach aphid (Myzus persicae). These phloem-limited viruses are acquired while aphids ingest phloem sap from infected plants. Here we found that co-infection decreased transmission of BChV by ∼50%, but had no impact on BYV transmission. The drastic reduction of BChV transmission was not due to lower accumulation of BChV in co-infected plants, nor to reduced phloem sap ingestion by aphids from these plants. Using the SABER-FISHin situhybridization technique on plants, we observed that 40% of the infected phloem cells were co-infected and that co-infection caused redistribution of BYV in these cells. The BYV accumulation pattern changed from distinct intracellular spherical inclusions in mono-infected cells to a diffuse form in co-infected cells. There, BYV co-localized with BChV throughout the cytoplasm, indicative of virus-virus interactions. We propose that BYV-BChV interactions could restrict BChV access to the sieve tubes and reduce its accessibility for aphids and present a model of how co-infection could alter BChV intracellular movement and/or phloem loading and reduce BChV transmission.IMPORTANCEMixed viral infections in plants are understudied yet can have significant influences on disease dynamics and virus transmission. We investigated how co-infection with two unrelated viruses, beet chlorosis virus (BChV) and beet yellows virus (BYV), affects aphid transmission of the viruses in sugar beet plants. We show that co-infection reduced BChV transmission by about 50% without affecting BYV transmission, despite similar virus accumulation rates in co-infected and mono-infected plants. Follow-up experiments examined the localization and intra-cellular distribution of the viruses, leading to the discovery that co-infection caused a redistribution of BYV in the phloem vessels and altered its repartition pattern within plant cells, suggesting virus-virus interactions. In conclusion, the interplay between BChV and BYV affects the transmission of BChV but not BYV, possibly through direct or indirect virus-virus interactions at the cellular level. Understanding these interactions could be crucial for managing virus propagation in crops and preventing yield losses.
A new method for detecting mixedMycobacterium tuberculosisinfection and reconstructing constituent strains provides insights into transmission
Authors: Sobkowiak Benjamin , Cudahy Patrick , Chitwood Melanie H. , Clark Taane G. , Colijn Caroline , Grandjean Louis , Walter Katharine S. , Crudu Valeriu , Cohen Ted 
Published: April 2024

AbstractBackgroundMixed infection with multiple strains of the same pathogen in a single host can present clinical and analytical challenges. Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we presentMixInfect2,a new tool to accurately detect mixed samples fromMycobacterium tuberculosisWGS data. We then evaluate three approaches for reconstructing the underlying mixed constituent strain sequences. This allows these samples to be included in downstream analysis to gain insights into the epidemiology and transmission of mixed infections.MethodsWe employed a Gaussian mixture model to cluster allele frequencies at mixed sites (hSNPs) in each sample to identify signals of multiple strains. Building upon our previous tool, MixInfect, we increased the accuracy of classifyingin vitromixed samples through multiple improvements to the bioinformatic pipeline. Major and minor proportion constituent strains were reconstructed using three approaches and assessed by comparing the estimated sequence to the known constituent strain sequence. Lastly, mixed infections in a real-worldMycobacterium tuberculosispopulation from Moldova were detected with MixInfect2 and clusters of recent transmission that included major and minor constituent strains were built.ResultsAll 36/36in vitromixed and 12/12 non-mixed samples were correctly classified with MixInfect2, and major strain proportions estimated with high accuracy, outperforming previous tools. Reconstructed major strain sequences closely matched the true constituent sequence by taking the allele at the highest frequency at hSNPs, while the best performing approach to reconstruct the minor proportion strain sequence was identifying the closest non-mixed isolate in the same population, though no approach was effective when the minor strain proportion was at 5%. Finally, fewer mixed infections were identified in Moldova than previous estimates (6.6% vs 17.4%) and we found multiple instances where the constituent strains of mixed samples were present in transmission clusters.ConclusionsMixInfect2 accurately detects samples with evidence of mixed infection from WGS data and provides an excellent estimate of the mixture proportions. While there are limitations in reconstructing the constituent strain sequences of mixed samples, we present recommendations for the best approach to include these isolates in further analyses.
Brain-wide arousal signals are segregated from movement planning in the superior colliculus
Authors: Johnston Richard , Smith Matthew A. 
Published: April 2024

AbstractThe superior colliculus (SC) is traditionally considered a brain region that functions as an interface between processing visual inputs and generating eye movement outputs. Although its role as a primary reflex center is thought to be conserved across vertebrate species, evidence suggests that the SC has evolved to support higher-order cognitive functions including spatial attention. When it comes to oculomotor areas such as the SC, it is critical that high precision fixation and eye movements are maintained even in the presence of signals related to ongoing changes in cognition and brain state, both of which have the potential to interfere with eye position encoding and movement generation. In this study, we recorded spiking responses of neuronal populations in the SC while monkeys performed a memory-guided saccade task and found that the activity of some of the neurons fluctuated over tens of minutes. By leveraging the statistical power afforded by high-dimensional neuronal recordings, we were able to identify a low-dimensional pattern of activity that was correlated with the subjects’ arousal levels. Importantly, we found that the spiking responses of deep-layer SC neurons were less correlated with this brain-wide arousal signal, and that neural activity associated with changes in pupil size and saccade tuning did not overlap in population activity space with movement initiation signals. Taken together, these findings provide a framework for understanding how signals related to cognition and arousal can be embedded in the population activity of oculomotor structures without compromising the fidelity of the motor output.
Somatosensory-evoked response induces extensive diffusivity and kurtosis changes associated with neural activity in rodents
Authors: Hertanu Andreea , Pavan Tommaso , Jelescu Ileana O. 
Published: April 2024

AbstractNeural tissue microstructure is dynamic during brain activity, presenting changes in cellular morphology and membrane permeability. The sensitivity of diffusion MRI (dMRI) to restrictions and hindrances in the form of cell membranes or subcellular structures enables the exploration of brain activity under a new paradigm, offering a more direct functional contrast than its BOLD counterpart. The current work aims at probing Mean Diffusivity (MD) and Mean Kurtosis (MK) changes and their time-dependence signature across various regions in the rat brain during somatosensory processing and integration, upon unilateral forepaw stimulation. We report adecreasein MD in the contralateral primary somatosensory cortex, forelimb region (S1FL), previously ascribed to cellular swelling and increased tortuosity in the extracellular space, paralleled by a positive BOLD response. For the first time, we also report a paireddecreasein MK during stimulation in S1FL, suggesting increased membrane permeability. This observation was further supported by the reduction in exchange time estimated from the kurtosis time-dependence analyses. Conversely, the secondary somatosensory cortex and subcortical areas, formerly reported as responsive to sensory stimulation in rodents (thalamus, striatum, hippocampal subfields), displayed a marked MD and MKincrease,paralleled by a weak-to-absent BOLD response. Overall, MD and MK uncovered functional-induced changes with higher sensitivity than BOLD. Although the exact origin of the MD and MK increase is yet to be unraveled, the potential of dMRI to provide complementary functional insights, even below the BOLD detection threshold, has been showcased.
Florigen-producing cells express FPF1-LIKE PROTEIN 1 that accelerates flowering and stem growth in long days with sunlight red/far-red ratio inArabidopsis
Authors: Takagi Hiroshi , Lee Nayoung , Hempton Andrew K. , Purushwani Savita , Notaguchi Michitaka , Yamauchi Kota , Shirai Kazumasa , Kawakatsu Yaichi , Uehara Susumu , Albers William G. , Downing Benjamin L. R. , Ito Shogo , Suzuki Takamasa , Matsuura Takakazu , Mori Izumi C. , Mitsuda Nobutaka , Kurihara Daisuke , Matsushita Tomonao , Song Young Hun , Sato Yoshikatsu , Nomoto Mika , Tada Yasuomi , Hanada Kousuke , Cuperus Josh T. , Queitsch Christine , Imaizumi Takato 
Published: April 2024

SummarySeasonal changes in spring induce flowering by expressing the florigen, FLOWERING LOCUS T (FT), inArabidopsis.FTis expressed in unique phloem companion cells with unknown characteristics. The question of which genes are co-expressed withFTand whether they have roles in flowering remains elusive. Through tissue-specific translatome analysis, we discovered that under long-day conditions with the natural sunlight red/far-red ratio, theFT-producing cells express a gene encoding FPF1-LIKE PROTEIN 1 (FLP1). The masterFTregulator, CONSTANS (CO), controlsFLP1expression, suggestingFLP1’s involvement in the photoperiod pathway. FLP1 promotes early flowering independently ofFT,is active in the shoot apical meristem, and induces the expression ofSEPALLATA 3(SEP3), a key E-class homeotic gene. Unlike FT, FLP1 facilitates inflorescence stem elongation. Our cumulative evidence indicates that FLP1 may act as a mobile signal. Thus, FLP1 orchestrates floral initiation together with FT and promotes inflorescence stem elongation during reproductive transitions.
Variation in the Distribution of Large-scale Spatiotemporal Patterns of Activity Across Brain States
Authors: Meyer-Baese Lisa , Anumba Nmachi , Bolt T , Daley L , LaGrow TJ , Zhang Xiaodi , Xu Nan , Pan Wen-Ju , Schumacher E , Keilholz Shella 
Published: April 2024

AbstractA few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.
Site saturation mutagenesis of 500 human protein domains reveals the contribution of protein destabilization to genetic disease
Authors: Beltran Antoni , Jiang Xiang’er , Shen Yue , Lehner Ben 
Published: April 2024

AbstractMissense variants that change the amino acid sequences of proteins cause one third of human genetic diseases1. Tens of millions of missense variants exist in the current human population, with the vast majority having unknown functional consequences. Here we present the first large-scale experimental analysis of human missense variants across many different proteins. Using DNA synthesis and cellular selection experiments we quantify the impact of >500,000 variants on the abundance of >500 human protein domains. This dataset, Human Domainome 1, reveals that >60% of pathogenic missense variants reduce protein stability. The contribution of stability to protein fitness varies across proteins and diseases, and is particularly important in recessive disorders. Combining stability measurements with protein language models annotates functional sites across proteins. Mutational effects on stability are largely conserved in homologous domains, allowing accurate stability prediction across entire protein families using energy models. Domainome 1 demonstrates the feasibility of assaying human protein variants at scale and provides a large consistent reference dataset for clinical variant interpretation and the training and benchmarking of computational methods.
Peaks and Distributions of White Matter Tract-related Strains in Bicycle Helmeted Impacts: Implication for Helmet Ranking and Optimization
Authors: Zhou Zhou , Fahlstedt Madelen , Li Xiaogai , Kleiven Svein 
Published: April 2024

AbstractTraumatic brain injury (TBI) in cyclists is a growing public health problem, with helmets being the major protection gear. Finite element head models have been increasingly used to engineer safer helmets often by mitigating brain strain peaks. However, how different helmets alter the spatial distribution of brain strain remains largely unknown. Besides, existing research primarily used maximum principal strain (MPS) as the injury parameter, while white matter fiber tract-related strains, increasingly recognized as effective predictors for TBI, have rarely been used for helmet evaluation. To address these research gaps, we used an anatomically detailed head model with embedded fiber tracts to simulate fifty-one helmeted impacts, encompassing seventeen bicycle helmets under three impact locations. We assessed the helmet performance based on four tract-related strains characterizing the normal and shear strain oriented along and perpendicular to the fiber tract, as well as the prevalently used MPS. Our results showed that both the helmet model and impact location affected the strain peaks. Interestingly, we noted that helmets did not alter strain distribution, except for one helmet under one specific impact location. Moreover, our analyses revealed that helmet ranking outcome based on strain peaks was affected by the choice of injury metrics (Kendall’s tau coefficient: 0.58 ∼ 0.93). Significant correlations were noted between tract-related strains and angular motion-based injury metrics. This study provided new insights into computational brain biomechanics and highlighted the helmet ranking outcome was dependent on the choice of injury metrics. Our results also hinted that the performance of helmets could be augmented by mitigating the strain peak and optimizing the strain distribution with accounting the selective vulnerability of brain subregions, although more research was needed to develop region-specific injury criteria.
Effects of social position on subsequent courtship and mating activity in an African cichlid
Authors: Martashvili Anastasia , Jedwab Sara , Vij Lakshita , Kuighadush Avraham Zion , Alvarado S.G. 
Published: April 2024

AbstractWithin social hierarchies, rank can be dynamic and modulated by changes in molecular and/or physiological substrates. Here, we sought to better understand how social environment and rank shape male spawning behaviors and outcomes in African cichlid fishAstatotilapia burtoni. First, using a social dyad paradigm, we generated territorial (T)/ Non-territorial (NT) male pairs. After establishing a stable social hierarchy, the behaviors of the Ts and NTs were recorded and scored. Afterward, pairs were separated and individually moved into a spawning phase, which consisted of a new tank with novel females and no other males where their behaviors were scored. While previous studies have shown how territorial and non-territorial males have unique behavioral profiles, we sought to deepen this interpretation with a focus on the latency of decision-making, and on transition matrices representing enriched sequences of behavior. We found that while the courtship behaviors are shared between stably territorial and ascending males in the spawning phase, only the animals that were territorial in the dyad phase were the ones that were reproductively successful in the subsequent 16 hour spawning phase.
Advancing cooperative breeding research with a peer-reviewed and “live” Cooperative-Breeding Database (Co-BreeD)
Authors: Mocha Yitzchak Ben , Woith Maike , Drobniak Szymon M. , Markman Shai , Frisoni Francesca , Baglione Vittorio , Boersma Jordan , Cousseau Laurence , Covas Rita , Braga de Miranda Guilherme Henrique , Dey Cody J. , Doutrelant Claire , Gula Roman , Heinsohn Robert , Kingma Sjouke A. , Li Jianqiang , Middleton Kyle-Mark , Radford Andrew N. , Restrepo Carla , Rubenstein Dustin R. , Schradin Carsten , Theuerkauf Jörn , Warrington Miyako H. , Williams Dean A. , Woxvold Iain A. , Griesser Michael 
Published: April 2024

AbstractResearch on cooperative breeding (a system with the core characteristic of individuals providing care for the offspring of others) is important for understanding sociality and cooperation. However, large-scale comparative analyses on the drivers and consequences of cooperation frequently use considerably inaccurate datasets (e.g. due to inconsistent definitions and outdated information). To advance comparative research on cooperative breeding, we introduce theCooperative-BreedingDatabase (Co-BreeD), a growing database of key socio-biological parameters of birds and mammals. First, we describe Co-BreeD’s structure as a (i) sample-based (i.e. multiple samples per species linked to an exact sampling location and period), (ii) peer-reviewed and (iii) updatable resource. Respectively, these curating principles allow for (i) investigating intra- and inter-species variation and linking between fine-scale social and environmental parameters, (ii) accuracy and (iii) continuous correction and expansion with the publication of new data. Second, we present the first Co-BreeD dataset, which estimates the prevalence of breeding events with potential alloparents in 265 samples from 233 populations of 150 species, including 2 human societies (N = 26,366 breeding events). We conclude by demonstrating (i) how Co-BreeD facilitates more accurate comparative research (e.g. increased explanatory power by enabling the study of cooperative breeding as a continuous trait, and statistically accounting for the sampling error probabilities), and (ii) that cooperative breeding in birds and mammals is more prevalent than currently estimated.