bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drosophila epidermal cells are intrinsically mechanosensitive and modulate nociceptive behavioral outputs
Authors: Yoshino Jiro , Mali Sonali S. , Williams Claire R. , Morita Takeshi , Emerson Chloe E. , Arp Christopher J. , Miller Sophie E. , Yin Chang , Thé Lydia , Hemmi Chikayo , Motoyoshi Mana , Ishii Kenichi , Emoto Kazuo , Bautista Diana M. , Parrish Jay Z. 
Published: October 2022

AbstractSomatosensory neurons (SSNs) that detect and transduce mechanical, thermal, and chemical stimuli densely innervate an animal’s skin. However, although epidermal cells provide the first point of contact for sensory stimuli. our understanding of roles that epidermal cells play in SSN function, particularly nociception, remains limited. Here, we show that stimulatingDrosophilaepidermal cells elicits activation of SSNs including nociceptors and triggers a variety of behavior outputs, including avoidance and escape. Further, we find that epidermal cells are intrinsically mechanosensitive and that epidermal mechanically evoked calcium responses require the store-operated calcium channel Orai. Epidermal cell stimulation augments larval responses to acute nociceptive stimuli and promotes prolonged hypersensitivity to subsequent mechanical stimuli. Hence, epidermal cells are key determinants of nociceptive sensitivity and sensitization, acting as primary sensors of noxious stimuli that tune nociceptor output and drive protective behaviors.
Talin and kindlin cooperate to control the density of integrin clusters
Authors: Pernier Julien , Dos Santos Marcelina Cardoso , Souissi Mariem , Joly Adrien , Narassimprakash Hemalatha , Rossier Olivier , Giannone Grégory , Helfer Emmanuèle , Sengupta Kheya , Le Clainche Christophe 
Published: October 2022

AbstractFocal adhesions are important mechanosensitive structures, composed of transmembrane integrins, linking the extracellular matrix to the actomyosin cytoskeleton, via cytoplasmic proteins. Cellular adhesion to the extracellular matrix depends on the activation of integrins by intracellular mechanisms. Talin and kindlin are major activators of integrins that are recruited to the inner membrane and bind to β-integrin cytoplasmic tails. Many studies showed the importance of integrin activation and clustering and how the organization of extracellular ligands guides the nanoscale organization of adhesion complexes. However, the roles of talin and kindlin in this process are poorly understood. To determine the contribution of talin, kindlin, lipids and actomyosin in integrin clustering, we performed experiments using a biomimetic in vitro system, made of Giant Unilamellar Vesicles, containing transmembrane integrins, on which purified talin, kindlin, and actomyosin assemble. Here we first show that talin and kindlin individually have the ability to cluster integrins. When added together, talin and kindlin synergize to induce the formation of larger integrin clusters containing the three proteins. Comparison of protein density in the talin-integrin, kindlin-integrin, and talin-kindlin-integrin clusters reveals that kindlin increases talin and integrin density, whereas talin does not affect kindlin and integrin density. Finally, kindlin significantly enhances the segregation of talin-integrin clusters induced by actomyosin contractility, suggesting that it increases the coupling of these clusters to the actin cytoskeleton. Our study unambiguously demonstrates how kindlin and talin cooperate to induce integrin clustering, which is a major parameter for cell adhesion.
The conserved upstream ORF of the ArabidopsisANAC082gene mediates translational upregulation in response to nucleolar stress
Authors: Sasaki Shun , Murakami Toru , Yasumuro Miharu , Makita Ayaka , Oi Yutaro , Hiragori Yuta , Watanabe Shun , Kudo Rin , Hayashi Noriya , Ohbayashi Iwai , Sugiyama Munetaka , Yamashita Yui , Naito Satoshi , Onouchi Hitoshi 
Published: October 2022

AbstractPerturbations in ribosome biogenesis cause a type of cellular stress called nucleolar or ribosomal stress, which triggers adaptive responses in both animal and plant cells. The Arabidopsis ANAC082 transcription factor has been identified as a key mediator of the plant nucleolar stress response. The 5′-untranslated region (5′-UTR) ofANAC082mRNA contains an upstream ORF (uORF) encoding an evolutionarily conserved amino acid sequence. Here, we report that this uORF mediates the upregulation ofANAC082translation in response to nucleolar stress. When transgenic Arabidopsis plants containing a luciferase reporter gene under the control of theANAC082promoter and 5′-UTR were treated with reagents that induced nucleolar stress, translation of the reporter gene was enhanced in a uORF sequence-dependent manner. Additionally, we examined the effect of an endoplasmic reticulum (ER) stress-inducing reagent on reporter gene expression because the closest homolog ofANAC082in Arabidopsis,ANAC103, is involved in the ER stress response. However, theANAC082uORF did not respond to ER stress. Interestingly, althoughANAC103has a uORF with an amino acid sequence similar to that of theANAC082uORF, the C-terminal sequence critical for regulation is not well conserved amongANAC103homologs in Brassicaceae. Transient expression assays revealed that unlike theANAC082uORF, theANAC103uORF does not exert a sequence-dependent regulatory effect. Altogether, our findings suggest that theANAC082uORF is important for the nucleolar stress response but not for the ER stress response, and that for this reason, the uORF sequence-dependent translational regulation was lost inANAC103during evolution.
Mapping connectivity and conservation opportunity on agricultural lands across the conterminous United States
Authors: Suraci Justin P. , Littlefield Caitlin E. , Nicholson Charlie C. , Hunter Mitchell C. , Sorensen Ann , Dickson Brett G. 
Published: October 2022

AbstractDepending on management practices, agricultural lands can either pose substantial barriers to the movement of native species or can support landscape connectivity by linking areas of high-quality habitat. Balancing connectivity and sustainable food production on agricultural lands is critical to conservation in the conterminous United States (CONUS) where agriculture makes up close to half of total land area. However, limited guidance exists on where to target conservation resources to maximize benefits for native species and food security.To quantify the potential contribution of agricultural lands to the movement of organisms, we developed a novel method for estimating agricultural management intensity (based on remotely sensed temporal variation in vegetation cover on croplands and pastures) and incorporated these estimates into a CONUS-wide, circuit-theory based model of ecological flow connectivity. We then combined our connectivity results with data on the productivity, versatility, and resilience of agricultural lands (PVR) to identify conservation opportunities that support both biodiversity and food production.The highest levels of connectivity on agricultural lands occurred on relatively unmodified rangelands and on cropland and pasture in close proximity to large amounts of natural land cover.Mapping connectivity and PVR across CONUS revealed 10.2 Mha of agricultural lands (2.7%) with high value for both connectivity and food production, as well as large amounts of agricultural land (>140 Mha in total) with high value for either cultivation or supporting biodiversity (e.g., through ecological restoration).Drawing on these findings, we provide recommendations on the types of conservation approaches most suitable for a given agricultural system and link these recommendations to specific government incentive programs. To help facilitate conservation planning based on our results, we have developed an interactive web application, allowing users to visualize the spatial data developed here within their regions of interest.
Entorhinal grid-like codes and time-locked network dynamics track others navigating through space
Authors: Wagner Isabella C. , Graichen Luise P. , Todorova Boryana , Lüttig Andre , Omer David B. , Stangl Matthias , Lamm Claus 
Published: October 2022

AbstractNavigating through crowded, dynamically changing social environments requires the ability to keep track of other individuals. Grid cells in the entorhinal cortex are a central component of self-related navigation but whether they also track others’ movement is unclear. Here, we propose that entorhinal grid-like codes make an essential contribution to socio-spatial navigation. Sixty human participants underwent functional magnetic resonance imaging (fMRI) while observing and re-tracing different paths of a demonstrator that navigated a virtual reality environment. Results revealed that grid-like codes in the entorhinal cortex tracked the other individual navigating through space. Further, the activity of grid-like codes was time-locked to increases in co-activation and entorhinal-cortical connectivity that included the striatum, the hippocampus, parahippocampal and right posterior parietal cortices, altogether modulated by accuracy when subsequently re-tracing the paths. This suggests that network dynamics time-locked to entorhinal grid-cell-related activity might serve to distribute information about the ‘socio-spatial map’ throughout the brain.
2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors
Authors: Ren Xiao-Min , Chang Richard C. , Huang Yikai , Amato Angélica Amorim , Carivenc Coralie , Grimaldi Marina , Kuo Angela Y. , Balaguer Patrick , Bourguet William , Blumberg Bruce 
Published: October 2022

ABSTRACT2,4-di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. Here we asked whether 2,4-DTBP is a potential obesogen. Using a human mesenchymal stem cell (MSC) adipogenesis assay, we found that exposure to 2,4-DTBP led to increased lipid accumulation and expression of adipogenic marker genes. Antagonist assays revealed that 2,4-DTBP increased lipid accumulation by activating the peroxisome proliferator-activated receptor γ (PPARγ)-retinoid X receptor (RXR) heterodimer. 2,4-DTBP likely activated the PPARγ/RXRα heterodimer by activating RXRα but not directly binding to PPARγ. We confirmed that 2,4-DTBP directly bound to RXRα by solving the crystal structure of this complex, then predicted and demonstrated that related compounds could also activate RXRα. Our study demonstrated that 2,4-DTBP and related chemicals could act as obesogens and endocrine disruptors via RXR. These data showed that 2,4-DTBP belongs to a family of compounds whose endocrine-disrupting and obesogenic effects can be strongly modulated by their chemical composition and that structure-activity studies such as the present one could help guide the rational development of safer antioxidants.SYNOPSISLittle research exists on the effects of commercially valuable antioxidants on biological systems. This study reports that di- and tri-tert-butylphenols can act as endocrine disruptors and potential obesogens by activating nuclear hormone receptors.
Multifunctional fibers enable modulation of cortical and deep brain activity during cognitive behavior in macaques
Authors: Garwood Indie C , Major Alex J , Antonini Marc-Joseph , Correa Josefina , Lee Youngbin , Sahasrabudhe Atharva , Mahnke Meredith K , Miller Earl K , Brown Emery N , Anikeeva Polina 
Published: October 2022

AbstractRecording and modulating neural activityin vivoenables investigations of neural circuits during behavior. However, there is a dearth of tools for simultaneous recording and localized receptor modulation in large animal models. We address this limitation by translating multifunctional fiber-based neurotechnology previously only available for rodent studies to enable cortical and subcortical neural modulation in macaques. We record single unit and local field potential activity before, during, and after intracranial GABA infusions in the premotor cortex and putamen. We apply state-space models to characterize changes in neural activity and investigate how neural activity evoked by a working memory task varies in the presence of local inhibition. The recordings provide detailed insight into the electrophysiological effect of neurotransmitter receptor modulation in both cortical and subcortical structures in an awake, behaving macaque. Our results demonstrate a first-time translation of multifunctional fibers for causal studies in behaving non-human primates.
Dysconnection and cognition in schizophrenia: a spectral dynamic causal modeling study
Authors: Zarghami Tahereh S. , Zeidman Peter , Razi Adeel , Bahrami Fariba , Hossein-Zadeh Gholam-Ali 
Published: October 2022

AbstractSchizophrenia (SZ) is a severe mental disorder characterized by failure of functional integration (aka dysconnection) across the brain. Recent functional connectivity (FC) studies have adopted functional parcellations to define subnetworks of large-scale networks, and to characterize the (dys)connection between them, in normal and clinical populations. While FC examines statistical dependencies between observations, model-based effective connectivity (EC) can disclose the causal influences that underwrite the observed dependencies. In this study, we investigated resting state EC between the subnetworks of seven large-scale networks, in 66 SZ and 74 healthy subjects from a public dataset. The results showed that a remarkable 33% of the effective connections (among subnetworks) of the cognitive control network had been pathologically modulated in SZ. Further dysconnection was identified within the visual, default mode and sensorimotor networks of SZ subjects, with 24%, 20% and 11% aberrant couplings. Overall, the proportion of diagnostic connections was remarkably larger in EC (24%) than FC (1%) analysis. Subsequently, to study the neural correlates of impaired cognition in SZ, we conducted a canonical correlation analysis between the EC parameters and the cognitive scores of the patients. As such, the self-inhibitions of supplementary motor area and paracentral lobule (in the sensorimotor network) and the excitatory connection from parahippocampal gyrus to inferior temporal gyrus (in the cognitive control network) were significantly correlated with the social cognition, reasoning/problem solving and working memory capabilities of the patients. Future research can investigate the potential of whole-brain EC as a biomarker for diagnosis of brain disorders and for cognitive assessment.
Deep Local Analysis estimates effects of mutations on protein-protein interactions
Authors: Behbahani Yasser Mohseni , Laine Elodie , Carbone Alessandra 
Published: October 2022

AbstractThe spectacular advances in protein and protein complex structure prediction hold promises for the reconstruction of interactomes at large scale at the residue resolution. Beyond determining the 3D arrangement of interacting partners, modeling approaches should be able to sense the impact of sequence variations such as point mutations on the strength of the association. In this work, we report on DLA-mutation, a novel and efficient deep learning framework for accurately predicting mutation-induced binding affinity changes. It relies on a 3D-invariant description of local 3D environments at protein interfaces and leverages the large amounts of available protein complex structures through self-supervised learning. It combines the learnt representations with evolutionary information, and a description of interface structural regions, in a siamese architecture. DLA-mutation achieves a Pearson correlation coefficient of 0.81 on a large collection of more than 2000 mutations, and its generalization capability to unseen complexes is higher than state-of-the-art methods.
Longitudinal investigation of changes in resting-state co-activation patterns and their predictive ability in the zQ175 DN mouse model of Huntington’s disease
Authors: Adhikari Mohit H. , Vasilkovska Tamara , Cachope Roger , Tang Haiying , Liu Longbin , Keliris Georgios A. , Munoz-Sanjuan Ignacio , Pustina Dorian , Van der Linden Annemie , Verhoye Marleen 
Published: October 2022

AbstractHuntington’s disease (HD) is a neurodegenerative disorder caused by expanded (≥40) glutamine-encoding CAG repeats in the huntingtin gene, which leads to dysfunction and death of predominantly striatal and cortical neurons. While the genetic profile and behavioural signs of the disease are better known, changes in the functional architecture of the brain, especially before the behavioural symptoms become apparent, are not fully and consistently characterized. In this study, we sought markers at pre, early and late manifest states of phenotypic progression in the heterozygous (HET) zQ175 delta-neo (DN) mouse model, using resting-state functional magnetic resonance imaging (RS-fMRI). This mouse model shows molecular, cellular and circuitry alterations that resemble those seen in HD in humans. Specifically, we investigated, longitudinally, changes in co-activation patterns (CAPs) that are the transient states of brain activity constituting the resting-state networks (RSNs). Most robust changes in the temporal properties of CAPs occurred at the late manifest state; the durations of two anti-correlated CAPs, characterized by simultaneous co-activation of default-mode like network (DMLN) and co-deactivation of lateral-cortical network (LCN) and vice-versa, were reduced in the zQ175 DN HET animals compared to the wild-type mice. Changes in the spatial properties, measured in terms of activation levels of different brain regions, during CAPs were found at all three states and became progressively more pronounced at the manifest states. We then assessed the cross-validated predictive power of CAP metrics to distinguish HET animals from controls. Spatial properties of CAPs performed significantly better than the chance level at all three states with 80% classification accuracy at the early and late manifest states.
The effects of biological sex on estimates of persistent inward currents in the human lower limb
Authors: Jenz Sophia T. , Beauchamp James A. , Gomes Matheus M. , Negro Francesco , Heckman CJ , Pearcey Gregory E.P. 
Published: October 2022

ABSTRACTNon-invasive recordings of motor unit (MU) spike trains help us understand how the nervous system controls movement and how it adapts to various physiological conditions. The majority of study participants in human and non-human animal physiology studies are male, and it is assumed mechanisms uncovered in these studies are shared between males and females. However, sex differences in neurological impairment and physical performance warrant the study of sex as a biological variable in human physiology and performance. To begin addressing this gap in the study of biophysical properties of human motoneurons, we quantified MU discharge rates and estimates of persistent inward current (PIC) magnitude in both sexes by quantifying ΔF. We decomposed MU spike trains from the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SOL) using high-density surface electromyography and blind source separation algorithms. Ten participants of each sex performed slow triangular (10s up and down) isometric contractions to a peak of 30% of their maximum voluntary contraction. We then used linear mixed effects models to determine if peak discharge rate and ΔF were predicted by the fixed effects of sex, muscle, and their interaction. Despite a lack of significant sex-differences in peak discharge rates across all muscles, ΔF was larger (χ2(1)= 6.26,p= 0.012) in females (4.73 ± 0.242 pps) than males (3.81 ± 0.240 pps). These findings suggest that neuromodulatory drive, inhibitory input, and/or biophysical properties of motoneurons differ between the sexes and may contribute to differences in MU discharge patterns.KEY POINTS–Sex differences in motor unit studies have been revealed with greater inclusion of female participants, however, mechanisms for these differences remain unclear.–Estimates of persistent inward currents (i.e., ΔF)were greater in females than males in the tibialis anterior, medial gastrocnemius, and soleus muscles.–This suggests that neuromodulatory drive, monoaminergic signaling, or descending control may differ between the sexes.–Therefore, sex differences in estimates of PICs may provide a mechanism behind previously reported sex differences in motoneuron discharge patterns..
Structural insights into the complex of oncogenic KRas4BG12Vand Rgl2, a RalA/B activator
Authors: Tariq Mishal , Ikeya Teppei , Togashi Naoyuki , Fairall Louise , Kamei Syun , Mayooramurugan Sannojah , Abbott Lauren R. , Hasan Anab , Bueno-Alejo Carlos , Sukegawa Sakura , Romartinez-Alonso Beatriz , Muro Campillo Miguel Angel , Hudson Andrew J. , Ito Yutaka , Schwabe John W.R. , Dominguez Cyril , Tanaka Kayoko 
Published: October 2022

AbstractAbout a quarter of total human cancers carry mutations in Ras isoforms. Accumulating evidence suggests that small GTPases, RalA and RalB, and their activators, Ral guanine nucleotide exchange factors (RalGEFs), play an essential role in oncogenic Ras-induced signalling. We studied the interaction between human KRas4B and the Ras association (RA) domain of Rgl2 (Rgl2RA), one of the RA-containing RalGEFs. We show that the G12V oncogenic KRas4B mutation changes the interaction kinetics with Rgl2RA. The crystal structure of the KRas4BG12V: Rgl2RAcomplex shows a 2:2 heterotetramer where the Switch I and Switch II regions of each KRasG12Vinteract with both Rgl2RAmolecules. This structural arrangement is highly similar to the HRasE31K:RALGDSRAcrystal structure and is distinct from the well-characterised Ras:Raf complex. Interestingly, the G12V mutation was found at the dimer interface of KRas4BG12Vwith its partner. Our study reveals a potentially distinct mode of Ras:effector complex formation by RalGEFs, and offers a possible mechanistic explanation for how the oncogenic KRas4BG12Vhyperactivates the RalA/B pathway.
Usability evaluation of two new presentation modes of scientific articles for academic reading
Authors: Niu Lihui , Ou Shiyan 
Published: October 2022

PurposeThis study developed two presentation modes of scientific articles and evaluated their usability with user experiments.Design/methodology/approachTwo presentation modes of scientific articles, simply referred to as “genre presentation mode” and “argument presentation mode”, were constructed based on their genre structure and argument structure respectively. Their usability was evaluated by being compared against the existing RichHTML presentation mode in the experiments using eye-tracking and questionnaire methods.FindingsThe participants who were going to find the specific information of scientific articles rated the genre presentation mode higher than they did with either the argument or the RichHTML presentation mode for effectiveness. In contrast, those who were going to understand the general idea of scientific articles rated both the genre and argument presentation mode higher than they did with the RichHTML mode. In terms of efficiency, the participants took less reading time when the articles of non-native language were presented with the genre mode than they did when the articles were presented with the argument mode. When reading the articles in native language to understand the general idea, the participants took less reading time for the articles presented with the argument mode than they did for the articles presented with the genre mode. In comparison, they took less reading time when the articles were presented with the argument mode if they were going to find specific information. For satisfaction, the genre presentation mode was more popular than the argument mode and the RichHTML mode. However, the participants were less satisfied with the argument presentation mode than the other two when reading in native language and intending to find specific information.Originality/valueThe two presentation modes of scientific articles are found to improve the accuracy of information acquisition, shorten the total reading time and be more acceptable by readers.