bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphological evolution and diversity of pectoral fin skeletons in teleosts
Authors: Tanaka Yoshitaka , Miura Hiroki , Tamura Koji , Abe Gembu 
Published: May 2022

AbstractThe Teleostei class has the most species of the fishes. Members of this group have paired rostral appendages and pectoral fins, enabling refined movements in the water. Although teleosts live in a diverse set of environments, the skeletal pattern of pectoral fins in teleosts is considered to show little morphological variability. Here, in order to elucidate variations in pectoral fin skeletons and to identify their evolutionary processes, we compared the pectoral fin skeletons from 27 species of teleosts. We identified several variations and a diversity of pectoral fin skeletal patterns within some teleost groups. Taken together with previous reports on teleost skeletons, our findings reveal that in the course of teleost evolution, there are a mixture of conserved and non- conserved components in the pectoral fin skeletons of teleosts, and that teleosts may have experienced the variation and conservation of the number and shape of the proximal radials, the loss of the mesocoracoid, and the change in the distal radial-fin ray relationship.
Role of High Mobility Group B protein HmbA, orthologue of yeast Nhp6p in Aspergillus nidulans
Authors: Ámon J. , Varga G. , Pfeiffer I. , Karácsony Z. , Hegedűs Z. , Vágvölgyi C. , Hamari Z. 
Published: May 2022

AbstractThe mammalian HMGB1 protein belongs to the high-mobility-group B (HMG-B) family, which is not only architectural but also functional element of the chromatin. The fungal counterpart of HMGB1 was identified in Saccharomyces cerevisiae as Nhp6p and the pleiotropic physiological functions of this protein were thoroughly studied during the last decades. Although filamentous Ascomycete fungi also possess the orthologues of Nhp6p, their physiological functions, apart from their role in the sexual development, have not been investigated, yet. Here we study the physiological functions of the Nhp6p orthologue HmbA from Aspergillus nidulans in the primary and secondary metabolism, stress tolerance, hypha elongation and maintenance of polarized growth through the analysis of hmbA deletion mutant. We also revealed that the endochitinase ChiA acts in the cell wall remodelling and contributes to polar growth. Additionally, by conducting heterologous expression studies, we further demonstrated that HmbA and Nhp6p is interchangeable for several functions. We hypothesized that the fully complemented functions might predominantly depend on the DNA binding ability of the HmbA and Nhp6p proteins rather than on the interaction of these HMG-B proteins with other functional protein components of the chromatin.
Katanin is involved in Microtubule Polymerization into Dendritic Spines and regulates Synaptic Plasticity
Authors: Lombino Franco L. , Schwarz Jürgen R. , Pechmann Yvonne , Schweizer Michaela , Glatzel Markus , Gee Christine E. , Gromova Kira V. , Kneussel Matthias 
Published: May 2022

AbstractDynamic microtubules transiently polymerize into dendritic spines, however intracellular factors that regulate this process and their functional role at synapses are hardly understood. Using live imaging, electrophysiology, and glutamate uncaging, we show that the microtubule-severing complex katanin is located at individual spine synapses, participates in the activity-dependent process of microtubule polymerization into dendritic spines, and regulates synaptic plasticity. Overexpression of a dominant-negative ATPase-deficient katanin subunit, did not alter microtubule growth velocities or comet density in dendrites, but significantly reduced the activity-dependent invasion of microtubules into dendritic spines. Notably, functional inhibition of katanin significantly affected the potentiation of AMPA-receptor-mediated excitatory currents after chemical induction of long-term potentiation (cLTP). Furthermore, interference with katanin function prevented structural spine remodeling following single spine glutamate uncaging. Our data identify katanin at individual spine synapses in association with PSD-95. Thus, katanin regulates postsynaptic microtubules and modulates synaptic structure and function.
Early structural connectivity within the sensorimotor network: deviations related to prematurity and association to neurodevelopmental outcome
Authors: Sara Neumane , Andrea Gondova , Yann Leprince , Lucie Hertz-Pannier , Tomoki Arichi , Jessica Dubois 
Published: May 2022

AbstractThe sensorimotor (SM) network is crucial for optimal neurodevelopment. However, undergoing rapid maturation during the perinatal period, it is particularly vulnerable to preterm birth.Our work explores the prematurity impact on the microstructure and maturation of primary SM white matter (WM) tracts at term-equivalent age (TEA) and evaluates the relationships between these alterations and neurodevelopmental outcome.We analyzed diffusion MRI data from the developing Human Connectome Project (dHCP) database: 59 preterm (PT) low-risk infants scanned near TEA, compared to a control group of full-term (FT) neonates paired for age at MRI and sex. We dissected pairwise connections between primary SM cortices and subcortical structures using probabilistic tractography and evaluated their microstructure with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. In addition to tract- specific univariate analyses of diffusion metrics, we computed a maturational distance related to prematurity based on a multi-parametric Mahalanobis distance of each PT infant relative to the FT group. Finally, we evaluated the relationships between this distance and Bayley Scales of Infant and Toddler Development (BSID-III) scaled scores at 18 months corrected age.Our results confirm important microstructural differences in SM tracts between PT and FT infants, with effects increasing with lower gestational age at birth. Additionally, comparisons of maturational distances highlight that prematurity has a differential effect on SM tracts which follows the established WM caudo-rostral developmental pattern. Our results suggest a particular vulnerability of projections involving the primary sensorimotor cortices (S1) and of the most rostral tracts, with cortico-cortical and S1-Lenticular tracts presenting the highest alterations at TEA. Finally, NODDI-derived maturational distances of specific tracts seem related to fine motor and cognitive scores.This study expands the understanding of the impact of early WM alterations in the emerging SM network on long-term neurodevelopment. In the future, related approaches have potential to lead to the development of neuroimaging markers for neurodevelopmental disorders, with special interest for subtle neuromotor impairments frequently observed in preterm-born children.
Effects of Body Mass on Leg and Vertical Stiffness in Running Humans
Authors: Fox Maria C. , Hsiao-Wecksler Elizabeth T. , Polk John D. 
Published: May 2022

AbstractNumerous cross-species comparisons have examined the scaling of gait parameters with respect to body mass (i.e., allometry), but few have done so within humans. This study examined how leg and vertical stiffness, force, displacement, and leg spring angle scaled in 64 healthy adults of varying body masses during slow and fast leg-length-adjusted running speeds. We calculated scaling patterns for stiffness and its components via kinematic and kinetic data using log-log regressions with 95% confidence/highest density intervals. To determine if the chosen statistical method influenced conclusions about scaling patterns, we compared regression results across three statistical methods, ordinary least squares (OLS) regression, linear mixed models (LMM), and Bayesian linear mixed models (BLMM). We also performed sex-specific analyses to determine if each sex revealed similar scaling patterns as the pooled sample. In the pooled sample, all variables scaled according to the isometric expectations, suggesting that different-sized humans move in a similar manner. Sex-specific analyses revealed similar patterns of isometry in all variables, except for vertical stiffness, which displayed slight negative allometry (i.e., lower than expected stiffness) in both sexes at the slow speed and negative allometry in females during fast running. Model choice did not significantly affect results, and scaling patterns were the same regardless of the statistical method employed.
The Tryptophan Metabolizing Enzyme Indoleamine 2,3-Dioxygenase 1 Regulates Polycystic Kidney Disease Progression
Authors: Nguyen Dustin T. , Kleczko Emily K. , Dwivedi Nidhi , Gitomer Berenice Y. , Chonchol Michel B. , Clambey Eric T. , Nemenoff Raphael A. , Klawitter Jelena , Hopp Katharina 
Published: May 2022

AbstractAutosomal dominant polycystic kidney disease (ADPKD), the most common monogenic nephropathy, is characterized by phenotypic variability exceeding genic effects. Dysregulated metabolism and immune cell function are key disease modulators. The tryptophan metabolites, kynurenines, produced through IDO1, are known immunomodulators. Here, we study the role of tryptophan metabolism in PKD using an orthologous disease model (C57Bl/6J Pkd1RC/RC). We found elevated kynurenine and IDO1 levels in Pkd1RC/RC kidneys versus wildtype. Further, IDO1 levels were increased in ADPKD cell lines and patient cyst cells. Genetic Ido1 loss in Pkd1RC/RC animals resulted in reduced PKD severity as measured by %kidney weight/body weight and cystic index. Consistent with a immunomodulatory role of kynurenines, Pkd1RC/RC;Ido1-/- mice presented with significant changes in the cystic immune microenvironment (CME) versus controls. Of note, kidney macrophage numbers decreased and CD8+ T cell numbers increased, both known PKD modulators. Also, pharmacological IDO1 inhibition using a tryptophan analog in Pkd1RC/RC animals resulted in less severe PKD versus controls with similar changes in the CME as in the genetic model. Together, our data suggest that tryptophan metabolism is dysregulated in ADPKD and that its inhibition results in changes to the CME and slows disease progression, making IDO1 a novel therapeutic target for ADPKD.
Physics of Self-Assembly and Morpho-Topological Changes of Klebsiella Pneumoniae in Desiccating Sessile Droplets
Authors: Rasheed Abdur , Hegde Omkar , Chaterjee Ritika , Sampathirao Srinivas Rao , Chakravortty Dipshikha , Basu Saptarshi 
Published: May 2022

AbstractWe have investigated the flow and desiccation-driven self-assembly of Klebsiella Pneumoniae in the naturally evaporating sessile droplets. Klebsiella Pneumoniae exhibits extensive changes in its morphology and forms unique patterns as the droplet dries, revealing hitherto unexplored rich physics governing its survival and infection strategies. Self-assembly of bacteria at the droplet contact line is characterized by order-to-disorder packing transitions with high packing densities and excessive deformations (bacteria deforms nearly twice its original length scales). In contrast, thin-film instability-led hole formation at the center of the droplet engenders spatial packing of bacteria analogous to honeycomb weathering. The varying physical forces acting on bacteria based on their respective spatial location inside the droplet cause an assorted magnitude of physical stress. Self-assembly favors the bacteria at the rim of the droplet, leading to enhanced viability and pathogenesis on the famously known “coffee ring” of the droplet compared to the bacteria present at the center of the droplet residue. Mechanistic insights gained via our study can have far-reaching implications for bacterial infection through droplets, e.g., through open wounds.
Spt6 directly interacts with Cdc73 and is required for Paf1C recruitment to active genes
Authors: Ellison Mitchell A. , Blacksmith Matthew S. , Namjilsuren Sanchirmaa , Shirra Margaret K. , Schusteff Rachel A. , Kerr Eleanor M. , Fang Fei , Xiang Yufei , Shi Yi , Arndt Karen M. 
Published: May 2022

ABSTRACTPaf1C is a conserved transcription elongation factor that regulates transcription elongation efficiency, facilitates co-transcriptional histone modifications, and impacts molecular processes linked to RNA synthesis, such as polyA site selection. Coupling of the activities of Paf1C to transcription elongation requires its association with RNA polymerase II (Pol II). Mutational studies in yeast identified Paf1C subunits Cdc73 and Rtf1 as important mediators of Paf1C recruitment to Pol II on active genes. While the interaction between Rtf1 and the general elongation factor Spt5 is relatively well-understood, the interactions involving Cdc73 remain to be elucidated. Using an in vivo site-specific protein cross-linking strategy, we identified direct interactions between Cdc73 and two components of the elongation complex, the elongation factor Spt6 and the largest subunit of Pol II. Through in vitro protein binding assays and crosslinking/mass spectrometry, we show that Cdc73 and Spt6 can interact in the absence of additional factors and propose a binding interface. Rapid depletion of Spt6 dissociated Paf1 from chromatin and altered patterns of Paf1C-dependent histone modifications genome-wide. These results reveal previously unrecognized interactions between Cdc73 and the Pol II elongation complex and identify Spt6 as a key factor contributing to Paf1C recruitment to active genes in Saccharomyces cerevisiae.
The effects of physical and temporal certainty on locomotion with discrete underfoot perturbations
Authors: Kreter Nicholas , Lybbert Carter , Gordon Keith E. , Fino Peter C. 
Published: May 2022

AbstractBackgroundAmbulation over complex terrain requires active control of foot placement to maintain a normal kinematic relationship between the center of mass and base of support. Recent investigations have suggested that foot placement location may be selected to anticipate shifts to the underfoot center of pressure. However, it is unclear whether temporal affordance and physical certainty contribute to the selection of a perturbation-specific anticipatory strategy. This study investigates anticipatory and reactive locomotor strategies for repeated underfoot perturbations with varying levels of temporal certainty, temporal affordance, and physical certainty.MethodsThirteen healthy adults walked with random underfoot perturbations from a mechanized shoe. Temporal certainty was challenged by presenting the perturbations with or without warning. Temporal affordance was challenged by adjusting the timing of a warning tone before the perturbation. Physical certainty was challenged with conditions that included only eversion perturbations, only inversion perturbations, or both eversion and inversion perturbations. Linear-mixed effects models assessed the effect of each condition on the percent change of margin of stability and step width, respectively.ResultsFor temporally uncertain perturbations and perturbations with one stride or less of affordance, we observed few changes to step width or margin of stability. As affordance increased to two strides, participants adopted a wider step width in anticipation of the perturbation (p = 0.001). Physical certainty had little effect on gait for the step of the perturbation, but participants recovered normal gait sooner when the physical nature of the perturbation was predictable (p < 0.001).DiscussionDespite having information about the timing and magnitude of upcoming perturbations, individuals do not develop perturbation specific feedforward strategies but instead rely on feedback control to recover normal gait after a perturbation. However, physical certainty appears to improve the efficiency of the feedback controller and allows individuals to recover normal gait sooner.
Actin nano-architecture of phagocytic podosomes
Authors: Herron J. Cody , Hu Shiqiong , Watanabe Takashi , Nogueira Ana T. , Liu Bei , Kern Megan , Aaron Jesse , Taylor Aaron , Pablo Michael , Chew Teng-Leong , Elston Timothy C. , Hahn Klaus M. 
Published: May 2022

AbstractPodosomes are actin-enriched adhesion structures important for multiple cellular processes, including migration, bone remodeling, and phagocytosis. Here, we characterized the structure and organization of phagocytic podosomes using interferometric photoactivated localization microscopy (iPALM), a super-resolution microscopy technique capable of 15-20 nm resolution, together with structured illumination microscopy (SIM) and localization-based superresolution microscopy. Phagocytic podosomes were observed during frustrated phagocytosis, a model in which cells attempt to engulf micro-patterned IgG antibodies. For circular patterns, this resulted in regular arrays of podosomes with well-defined geometry. Using persistent homology, we developed a pipeline for semi-automatic identification and measurement of podosome features. These studies revealed an “hourglass” shape of the podosome actin core, a protruding “knob” at the bottom of the core, and two actin networks extending from the core. Additionally, the distributions of paxillin, talin, myosin II, α-actinin, cortactin, and microtubules relative to actin were characterized.
Contributions and synaptic basis of diverse cortical neuron responses to task performance
Authors: Insanally Michele N. , Albanna Badr F. , Toth Jack , DePasquale Brian , Fadaei Saba , Gupta Trisha , Kuchibhotla Kishore , Rajan Kanaka , Froemke Robert C. 
Published: May 2022

AbstractNeuronal responses during behavior are diverse, ranging from highly reliable ‘classical’ responses to irregular or seemingly-random ‘non-classically responsive’ firing. While a continuum of response properties is frequently observed across neural systems, little is known about the synaptic origins and contributions of diverse response profiles to network function, perception, and behavior. Here we use a task-performing, spiking recurrent neural network model incorporating spike-timing-dependent plasticity that captures heterogeneous responses measured from auditory cortex of behaving rodents. Classically responsive and non-classically responsive model units contributed to task performance via output and recurrent connections, respectively. Excitatory and inhibitory plasticity independently shaped spiking responses and task performance. Local patterns of synaptic inputs predicted spiking response properties of network units as well as the responses of auditory cortical neurons from in vivo whole-cell recordings during behavior. Thus a diversity of neural response profiles emerges from synaptic plasticity rules with distinctly important functions for network performance.
Involvement of Lateral Habenula Dysfunction in Repetitive Mild Traumatic Brain Injury-Induced Motivational Deficits
Authors: Flerlage William J. , Langlois Ludovic D. , Rusnak Milan , Simmons Sarah C. , Gouty Shawn , Armstrong Regina C. , Cox Brian M. , Symes Aviva J. , Tsuda Mumeko C. , Nugent Fereshteh S. 
Published: May 2022

AbstractAffective disorders including depression (characterized by reduced motivation, social withdrawal and anhedonia), anxiety and irritability are frequently reported as long-term consequences of mild traumatic brain injury (mTBI)1 in addition to cognitive deficits, suggesting a possible dysregulation within mood/motivational neural circuits. One of the important brain regions that control motivation and mood is the lateral habenula (LHb) whose hyperactivity is associated with depression2. Here we used a repetitive closed head injury mTBI model that is associated with social deficits in adult male mice3 and explored the possible long-term alterations in LHb activity and motivated behavior 10-14 days post-injury. We found that mTBI increased the proportion of spontaneous tonically active LHb neurons while decreased LHb bursting. Additionally, mTBI diminished spontaneous glutamatergic and GABAergic synaptic activity onto LHb neurons, while synaptic excitation and inhibition (E/I) balance was shifted toward excitation through a greater suppression of GABAergic transmission. Behaviorally, mTBI increased the latency in grooming behavior in sucrose splash test suggesting reduced self-care motivated behavior following mTBI. To show whether limiting LHb hyperactivity could restore motivational deficits in grooming behavior, we then tested the effects of Gi (hM4Di)-DREADD-mediated inhibition of LHb activity in sucrose splash test. We found that chemogenetic inhibition of LHb glutamatergic neurons was sufficient to reverse mTBI-induced delays in grooming behavior. Overall, our study provides the first evidence for persistent LHb neuronal dysfunction due to an altered synaptic integration as causal neural correlates of dysregulated motivational states by mTBI.
Novel Computational Models of Evoked Dopamine Release In Vivo Measured by Fast Scan Cyclic Voltammetry Quantify the Regulation of Presynaptic Kinetics by Synucleins
Authors: Shashaank N , Somayaji Mahalakshmi , Miotto Mattia , Mosharov Eugene V. , Knowles David A. , Ruocco Giancarlo , Sulzer David L. 
Published: May 2022

AbstractDopamine neurotransmission in the striatum is central to many normal and disease functions. Ventral midbrain dopamine neurons exhibit ongoing tonic firing that produce low extrasynaptic levels of dopamine below the detection of extrasynaptic electrochemical recordings (∼10 – 20 nanomolar), with superimposed bursts that can saturate the dopamine uptake transporter and produce transient micromolar concentrations. The bursts have previously been shown to lead to presynaptic plasticity via multiple mechanisms, but analysis methods for these kinetic parameters are limited. To provide a deeper understanding of the mechanics of dopamine neurotransmission, we present three computational models of dopamine release with different levels of spatiotemporal complexity to analyze in vivo fast-scan cyclic voltammetry recordings from the dorsal striatum of mice. The models accurately fit to the cyclic voltammetry data and provide estimates of presynaptic dopamine facilitation/depression kinetics and dopamine transporter reuptake kinetics. We use the models to analyze the role of synuclein proteins in neurotransmission and quantify recent findings linking presynaptic protein α-synuclein to the short-term facilitation and long-term depression of dopamine release.