bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL7Rα is required for hematopoietic stem cell reconstitution of tissue-resident lymphoid cells
Authors: Worthington Atesh K. , Cool Taylor S. , Poscablo Donna M. , Hussaini Adeel , Beaudin Anna E. , Forsberg E. Camilla 
Published: July 2021

ABSTRACTTraditional, adult-derived lymphocytes that circulate provide adaptive immunity to infection and pathogens. However, subsets of lymphoid cells are also found in non-lymphoid tissues and are called tissue-resident lymphoid cells (TLCs). TLCs encompass a wide array of cell types that span the spectrum of innate-to-adaptive immune function. Unlike traditional lymphocytes that are continuously generated from hematopoietic stem cells (HSCs), many TLCs are of fetal origin and poorly generated from adult HSCs. Here, we sought to understand the development of murine TLCs across multiple tissues and therefore probed the roles of Flk2 and IL7Rα, two cytokine receptors with known roles in traditional lymphopoiesis. Using Flk2- and Il7r-Cre lineage tracing models, we found that peritoneal B1a cells, splenic marginal zone B (MZB) cells, lung ILC2s and regulatory T cells (Tregs) were highly labeled in both models. Despite this high labeling, highly quantitative, in vivo functional approaches showed that the loss of Flk2 minimally affected the generation of these cells in situ. In contrast, the loss of IL7Rα, or combined deletion of Flk2 and IL7Rα, dramatically reduced the cell numbers of B1a cells, MZBs, ILC2s, and Tregs both in situ and upon transplantation, indicating an intrinsic and more essential role for IL7Rα. Surprisingly, reciprocal transplants of WT HSCs showed that an IL7Rα-/- environment selectively impaired reconstitution of TLCs when compared to TLC numbers in situ. Taken together, our data revealed functional roles of Flk2 and IL7Rα in the establishment of tissue-resident lymphoid cells.
Citrus photosynthesis and morphology acclimate to phloem-affecting huanglongbing disease at the leaf and shoot levels
Authors: Keeley Mark , Rowland Diane , Vincent Christopher 
Published: July 2021

AbstractHuanglongbing (HLB) is a phloem-affecting disease of citrus that reduces growth and has impacted global citrus production. HLB is caused by a phloem-limited bacterium (CandidatusLiberibacter asiaticus;CLas). By inhibiting phloem function, HLB stunts sink growth, including reducing production of new shoots and leaves, and induces hyperaccumulation of foliar starch. HLB induces feedback inhibition of photosynthesis by reducing foliar carbohydrate export. In this work we assessed the relationship of bacterial distribution within the foliage, foliar starch accumulation, and net CO2assimilation (Anet). Because HLB impacts canopy morphology, we developed a chamber to measure whole-shootAnetto test the effects of HLB at both leaf and shoot levels. Whole-shoot-levelAnetsaturated at high irradiance, and green stems had high photosynthetic rates compared to leaves. Starch accumulation was correlated with bacterial population, and starch was negatively correlated withAnetat the leaf level but not at the shoot level. Starch increased initially after infection, then decreased progressively with increasing length of infection. HLB infection reducedAnetat the leaf level, but increased it at the whole shoot level, in association with reduced leaf size and greater relative contribution of stems to photosynthetic surface area. Although HLB-increased photosynthetic efficiency, total carbon fixed per shoot decreased because photosynthetic surface area was reduced. We conclude that the localized effects of infection on photosynthesis are mitigated by whole shoot morphological acclimation over time. Stems contribute important proportions of whole shootAnet, and these contributions are likely increased by the morphological acclimation induced by HLB.
Enhanced transcriptional heterogeneity mediated by NF-κB super-enhancers
Authors: Wibisana Johannes N. , Inaba Takehiko , Shinohara Hisaaki , Yumoto Noriko , Hayashi Tetsutaro , Umeda Mana , Ebisawa Masashi , Nikaido Itoshi , Sako Yasushi , Okada Mariko 
Published: July 2021

AbstractThe transcription factor NF-κB, which plays an important role in cell fate determination, is involved in the activation of super-enhancers (SEs). However, the biological functions of the NF-κB SEs in gene control are not fully elucidated. We investigated the characteristics of NF-κB-mediated SE activity using fluorescence live-cell imaging of RelA, single-cell transcriptome, and chromatin accessibility analyses in anti-IgM-stimulated B cells. Cell stimulation induced nuclear foci formation of RelA and gene expression in a switch-like manner. The gained SEs induced a higher fold-change expression and enhanced cell-to-cell variability in transcriptional response. These properties were correlated with the number of gained cis-regulatory interactions, while switch-like gene induction was associated with the number of NF-κB binding sites in SE. Our study suggests that NF-κB SEs have unique roles for quantitative control of gene expression through direct binding to accessible DNA and enhanced DNA contacts.
The role of reading experience in atypical cortical tracking of speech and speech-in-noise in dyslexia
Authors: Destoky Florian , Bertels Julie , Niesen Maxime , Wens Vincent , Ghinst Marc Vander , Rovai Antonin , Trotta Nicola , Lallier Marie , De Tiège Xavier , Bourguignon Mathieu 
Published: July 2021

AbstractDyslexia is a frequent developmental disorder in which reading acquisition is delayed and that is usually associated with difficulties understanding speech in noise. At the neuronal level, children with dyslexia were reported to display abnormal cortical tracking of speech (CTS) at phrasal rate. Here, we aimed to determine if abnormal tracking is a cause or a consequence of dyslexia and if it is modulated by the severity of dyslexia or the presence of acoustic noise.We included 26 school-age children with dyslexia, 26 age-matched controls and 26 reading-level matched controls. All were native French speakers. Children’s brain activity was recorded with magnetoencephalography while they listened to continuous speech in noiseless and multiple noise conditions. CTS values were compared between groups, conditions and hemispheres, and also within groups, between children with best and worse reading performance.Syllabic CTS was significantly reduced in the right superior temporal gyrus in children with dyslexia compared with controls matched for age but not for reading level. Among children with dyslexia, phrasal CTS tended to lateralize to the left hemisphere in severe dyslexia and lateralized to the right hemisphere in children with mild dyslexia and in all control groups. Finally, phrasal CTS was lower in children with dyslexia compared with age-matched controls, but only in informational noise conditions. No such effect was seen in comparison with reading-level matched controls.Overall, our results confirmed the finding of altered neuronal basis of speech perception in noiseless and babble noise conditions in dyslexia compared with age-matched peers. However, the absence of alteration in comparison with reading-level matched controls suggests that such alterations are a consequence of reduced reading experience rather than a cause of dyslexia.HighlightsThe cortical tracking of speech (CTS) was assessed in dyslexia and proper controlsPhrasal CTS and its resistance to noise were altered in dyslexiaSuch alterations were not found in comparison with controls matched for reading levelThe severity of dyslexia modulated the hemispheric lateralization of phrasal CTS
Turnover Regulation of the Rho GTPase Cdc42 by Heat Shock Protein Chaperones and the MAPK Pathway Scaffold Bem4
Authors: González Beatriz , Cullen Paul J. 
Published: July 2021

AbstractAll cells maintain an axis of polarity that directs the orientation of growth. Cell polarity can be reorganized during development and in response to extrinsic cues to produce new cell types. Rho GTPases are central regulators of cell polarity and signal-dependent cell differentiation. We show here that one of the best understood Rho GTPases, the highly conserved yeast Cdc42p, is turned over by members of the Heat Shock family of Proteins (HSPs). The Hsp40p chaperone, Ydj1p, was required for turnover of Cdc42p by the NEDD4 E3 ubiquitin ligase, Rsp5p, in the proteosome. Cdc42p turnover was regulated by HSPs at high temperatures, and in aging cells where the protein formed aggregates, implicating HSPs in Rho GTPase quality control. We also show that Cdc42pQ61L, which mimics the active (GTP-bound) conformation of the protein, was turned over at elevated levels by Ydj1p and Rsp5p. A turnover-defective version of Cdc42pQ61L led to multibudding phenotypes, implicating Cdc42 turnover in singularity in cell polarization. Cdc42p turnover also impacted MAP kinase pathway specificity. A pathway-specific scaffold, Bem4p, stabilized Cdc42p levels, which biased Cdc42p function in one MAPK pathway over another. Turnover regulation of Rho GTPases by HSPs and scaffolds provides new dimensions to the regulation of cell polarity and signal-dependent morphogenesis.Significance StatementRho GTPases are switch-like proteins that govern major decisions in cell polarity and signaling in eukaryotes. We elucidate here a pathway that turns over the yeast Rho GTPase Cdc42p, which is mediated by the heat-shock family of proteins (HSPs) and the NEDD4-type E3 ubiquitin ligase Rsp5p. This finding provides a way for HSPs to exert their widespread effects on morphogenetic responses, phenotypic plasticity, and signaling pathways. We also found that turnover of an active version of Cdc42p is critical for modulating cell polarity. Cdc42p turnover also impacted its function in a pathway specific setting, as stabilization of Cdc42p by Bem4p (SmgGDS-type scaffold) influenced the activity of a specific MAPK pathway. HSPs may regulate Rho GTPase turnover in many systems.
Global change differentially modulates coral physiology and suggests future shifts in Caribbean reef assemblages
Authors: Bove Colleen B , Davies Sarah W , Ries Justin B , Umbanhowar James , Thomasson Bailey C , Farquhar Elizabeth B , McCoppin Jessica A , Castillo Karl D 
Published: July 2021

AbstractGlobal change driven by anthropogenic carbon emissions is altering ecosystems at unprecedented rates, especially coral reefs, whose symbiosis with algal endosymbionts ise particularly vulnerable to increasing ocean temperatures and altered carbonate chemistry. Here, we assess the physiological responses of the coral holobiont (animal host + algal symbiont) of three Caribbean coral species from two reef environments after exposure to simulated ocean warming (28, 31 °C), acidification (300 - 3290 μatm), and the combination of stressors for 93 days. We used multidimensional analyses to assess how multiple coral holobiont physiological parameters respond to ocean acidification and warming. Our results demonstrate significantly diminishing holobiont physiology in S. siderea and P. astreoides in response to projected ocean acidification, while future warming elicited severe declines in P. strigosa. Offshore S. siderea fragments exhibited higher physiological plasticity than inshore counterparts, suggesting that this offshore population has the capacity to modulate their physiology in response to changing conditions, but at a cost to the holobiont. Plasticity of P. strigosa and P. astreoides was not clearly different between natal reef environments, however, temperature evoked a greater plastic response in both species. Interestingly, while these species exhibit unique physiological responses to ocean acidification and warming, when data from all three species are modeled together, convergent stress responses to these conditions are observed, highlighting the overall sensitivities of tropical corals to these stressors. Our results demonstrate that while ocean warming is a severe acute stressor that will have dire consequences for coral reefs globally, chronic exposure to acidification may also impact coral physiology to a greater extent than previously assumed. The variety of responses to global change we observe across species will likely manifest in altered Caribbean reef assemblages in the future.
Long-read isoform sequencing reveals tissue-specific isoform expression between active and hibernating brown bears (Ursus arctos)
Authors: Tseng Elizabeth , Underwood Jason G. , Evans Hutzenbiler Brandon D. , Trojahn Shawn , Kingham Brewster , Shevchenko Olga , Bernberg Erin , Vierra Michelle , Robbins Charles T. , Jansen Heiko T. , Kelley Joanna L. 
Published: July 2021

SummaryUnderstanding hibernation in brown bears (Ursus arctos) can provide insight into many human diseases. During hibernation, brown bears experience states of insulin resistance, physical inactivity, extreme bradycardia, obesity, and the absence of urine production. These states closely mimic human diseases such as type 2 diabetes, muscle atrophy, renal and heart failure, cachexia, and obesity. The reversibility of these states from hibernation to active season allows for the identification of novel mediators with possible therapeutic value for humans. Recent studies have identified genes and pathways that are differentially expressed between active and hibernation seasons. However, little is known about the role of differential expression of gene isoforms on hibernation physiology. To identify both distinct and novel mRNA isoforms, we performed full-length RNA-sequencing (Iso-Seq) on three tissue types from three individuals sampled during both active and hibernation seasons. We combined the long-read data with the reference annotation for an improved transcriptome and mapped RNA-seq data from six individuals to the improved transcriptome to quantify differential isoform usage between tissues and seasons. We identified differentially expressed isoforms in all study tissues and showed that adipose has a high level of differential isoform usage with isoform switching, regardless of whether the genes were differentially expressed. Our analyses provide a comprehensive evaluation of isoform usage between active and hibernation states, revealing that differential isoform usage, even in the absence of differential gene expression, is an important mechanism for modulating genes during hibernation. These findings demonstrate the value of isoform expression studies and will serve as the basis for deeper exploration into hibernation biology.
Apo and ligand-bound high resolution Cryo-EM structures of the human Kv3.1 reveal a novel binding site for positive modulators
Authors: Botte Mathieu , Huber Sophie , Bucher Denis , Klint Julie K. , Rodríguez David , Tagmose Lena , Chami Mohamed , Cheng Robert , Hennig Michael , Rahman Wassim Abdul 
Published: July 2021

AbstractKv3 ion-channels constitute a class of functionally distinct voltage gated ion channels characterized by their ability to fire at a high frequency. Several disease relevant mutants, together with biological data, suggest the importance of this class of ion channels as drug targets for CNS disorders, and several drug discovery efforts have been reported. Despite the increasing interest for this class of ion channels, no structure of a Kv3 channel has been reported yet. We have determined the cryo-EM structure of Kv3.1 at 2.6 Å resolution using full length wild type protein. When compared to known structures for potassium channels from other classes, a novel domain organization is observed with the cytoplasmic T1 domain, containing a well resolved Zinc site and displaying a rotation by 35°. This suggests a distinct cytoplasmic regulation mechanism for the Kv3.1 channel. A high resolution structure was obtained for Kv3.1 in complex with a novel positive modulator Lu AG00563. The structure reveals a novel ligand binding site for the Kv class of ion channels located between the voltage sensory domain and the channel pore, a region which constitutes a hotspot for disease causing mutations. The discovery of a novel binding site for a positive modulator of a voltage gated potassium channel could shed light on the mechanism of action for these small molecule potentiators. This finding could enable structure-based drug design on these targets with high therapeutic potential for the treatment of multiple CNS disorders.
Motor memories of object dynamics are categorically organized
Authors: Cesanek Evan , Zhang Zhaoran , Ingram James N. , Wolpert Daniel M. , Flanagan J. Randall 
Published: July 2021

AbstractThe ability to predict the dynamics of objects, linking applied force to motion, underlies our capacity to perform many of the tasks we carry out on a daily basis. Thus, a fundamental question is how the dynamics of the myriad objects we interact with are organized in memory. Using a custom-built three-dimensional robotic interface that allowed us to simulate objects of varying appearance and weight, we examined how participants learned the weights of sets of objects that they repeatedly lifted. We find strong support for the novel hypothesis that motor memories of object dynamics are organized categorically, in terms of families, based on covariation in their visual and mechanical properties. A striking prediction of this hypothesis, supported by our findings and not predicted by standard associative map models, is that outlier objects with weights that deviate from the family-predicted weight will never be learned despite causing repeated lifting errors.
Quantifying the size and healing of volumetric muscle wounds using 3D Slicer on CT scans in a canine model
Authors: Larie Dale , An Gary , Johnson Scott , Hoffman Kelly , Vodovotz Yoram , Badylak Stephen , Cockrell Chase 
Published: July 2021

AbstractVolumetric soft tissue and muscle wounds can arise from trauma or necrotizing soft tissue infection. Quantifying the size of these wounds can be challenging, as they often have irregular borders and contours and invariably involve skin loss. 3-dimensional Computed Tomography (3dCT) has been used to characterize the volume of numerous tissue structures, but these use cases invariably involve structures for which clear anatomic borders exist. This is not the case for volumetric soft tissue or muscle wounds, where the volume of the wound being assessed, which is actually a void representing the absence of tissue, does not contain an explicit border at the superficial surface. We present a method that allows quantification of the void size of volumetric muscle wounds using CT scans processed with the software package 3D Slicer. This quantification allows us to chart the progression of healing in such wounds with sequential scans. The development of a means to quantify wound size and healing rate is a necessary capability in order to assess the efficacy of potential therapeutic interventions aimed at enhancing healing of such wounds.
Disentangling temporal associations in marine microbial networks
Authors: Deutschmann Ina Maria , Krabberød Anders K. , Latorre Francisco , Delage Erwan , Marrasé Cèlia , Balagué Vanessa , Gasol Josep M. , Massana Ramon , Eveillard Damien , Chaffron Samuel , Logares Ramiro 
Published: July 2021

ABSTRACTBackgroundMicrobial interactions are fundamental for Earth’s ecosystem functioning and biogeochemical cycling. Nevertheless, they are challenging to identify and remain barely known. Omics-based censuses are helpful in predicting microbial interactions through the statistical inference of single (static) association networks. Yet, microbial interactions are dynamic and we have limited knowledge of how they change over time. Here we investigate the dynamics of microbial associations in a 10-year marine time series in the Mediterranean Sea using an approach inferring a time-resolved (temporal) network from a single static network.ResultsA single static network including microbial eukaryotes and bacteria was built using metabarcoding data derived from 120 monthly samples. For the decade, we aimed to identify persistent, seasonal, and temporary microbial associations by determining a temporal network that captures the interactome of each individual sample. We found that the temporal network appears to follow an annual cycle, collapsing and reassembling when transiting between colder and warmer waters. We observed higher association repeatability in colder than in warmer months. Only 16 associations could be validated using observations reported in literature, underlining our knowledge gap in marine microbial ecological interactions.ConclusionsOur results indicate that marine microbial associations follow recurrent temporal dynamics in temperate zones, which need to be accounted for to better understand the functioning of the ocean microbiome. The constructed marine temporal network may serve as a resource for testing season-specific microbial interaction hypotheses. The applied approach can be transferred to microbiome studies in other ecosystems.
Life history traits and dispersal shape neutral genetic diversity in metapopulations
Authors: Garnier Jimmy , Lafontaine Pierre 
Published: July 2021

AbstractGenetic diversity at population scale, depends on species life-history traits, population dynamics and local and global environmental factors. We first investigate the effect of life-history traits on the neutral genetic diversity of a single population using a deterministic mathematical model. When the population is stable, we show that semelparous species with precocious maturation and iteroparous species with delayed maturation exhibit higher diversity because their life history traits tend to balance the lifetimes of non reproductive individuals (juveniles) and adults which reproduce. Then, we extend our model to a metapopulation to investigate the additional effect of dispersal on diversity. We show that dispersal may truly modify the local effect of life history on diversity. As a result, the diversity at the global scale of the metapopulation differ from the local diversity which is only described through local life history traits of the populations. In particular, dispersal usually promotes diversity at the global metapopulation scale.
Morphological integration during postnatal ontogeny: implications for evolutionary biology
Authors: Hubbe Alex , Machado Fabio A. , Melo Diogo , Garcia Guilherme , Sebastião Harley , Porto Arthur , Cheverud James , Marroig Gabriel 
Published: July 2021

AbstractHow covariance patterns of phenotypes change during development is fundamental for a broader understanding of evolution. There is compelling evidence that mammalian skull covariance patterns change during ontogeny. However, it is unclear to what extent variation in covariance patterns during ontogeny can impact the response to selection. To tackle this question we explored: i) the extent to which covariance patterns change during postnatal ontogeny; ii) in which ontogenetic stages covariance patterns differ the most, and iii) the extent to which the phenotypic covariance pattern at different ontogenetic stages can be explained by the same processes determining additive genetic covariance. We sampled postnatal ontogenetic series for both marsupials, and placentals. Within each ontogenetic series, we compared covariance matrices (P-matrices) at different ontogenetic stages. Furthermore, we compared these P-matrices to two target matrices [adult P-matrix and an additive genetic covariance matrix (G-matrix)]. Our results show that for all ontogenetic series, covariance patterns from weaning onward are conserved and probably shaped by the same processes determining the G-matrix. We conclude that irrespective of eventual differences in how selection operates during most of postnatal ontogeny, the net response to such pressures will probably not be affected by ontogenetic differences in the covariance pattern.