Biology subjects

Kong, G.

Publications and source records attributed to Kong, G..

18 recordsLinked to original sources

bioRxiv2026

Inflammatory burning pain depends on a specific line of nociceptors

The development and persistence of burning pain and heat hyperalgesia following tissue injury and the subsequent inflammatory response, depend on the nuclear enzyme mitogen- and stress-activated kinase 1 (MSK1) expressed in a specific subset of transient receptor potential subfamily V member 1 (TRPV1)-expressing primary sensory neurons termed nociceptors, which are specialised for detecting harmful stimuli. Inflammation up-regulates and activates MSK1, and MSK1 governs TRPV1 expression in the MSK1 and TRPV1 co-expressing mouse and human nociceptors. Importantly, inhibition of inflammatory MSK1-mediated TRPV1 upregulation protects from heat hypersensitivity without affecting other relevant TRPV1 functions, such as the sensation of acute painful heat stimuli or the maintenance of the body core temperature. The newly discovered importance of the interaction between MSK1 and TRPV1 in a specific line of nociceptors provides mechanistic understanding of inflammatory pain and heat hyperalgesia pathogenesis.

neuroscience↗

bioRxiv2025

The sense of agency in near and far space: where do we stand?

Modern technology frequently places the consequences of our actions at a distance (e.g., remote surgery, smart-home control, virtual reality). Does spatial distance between an action and its outcome weaken the sense of agency (SoA) - the feeling of control over ones actions and consequences? Two recent studies answered "yes", reporting stronger temporal binding (TB) in near than far space and interpreting this as greater implicit agency (Jenkins & Obhi, 2021; Mariano et al., 2024). A third study - our own work with a similar paradigm - found no distance effect (Kong et al., 2024). Here we (i) provide a rigorous side-by-side methodological comparison of the three studies, (ii) argue why a direct test to establish a distance modulation of TB (the Near - Far difference of the Active - Passive delta) should be performed in order to reach meaningful conclusions, and (iii) report new re-analyses of our data and direct tests on the two target studies. Overall, current evidence does not support a distance effect on SoA. Our reassessment provides alternative explanations that converge with available evidence suggesting that distance may influence temporal interval perception, but that effect is independent of action intention and therefore of agency. Public Significance StatementIn our increasingly connected world, we often interact with devices and influence events that are physically distant from us - like controlling smart appliances remotely or engaging in virtual reality experiences. Does the distance between us and the effects of our actions change how much we feel in control of the outcomes of our actions? Recent studies have suggested that we feel less responsible when action outcomes appear in far space compared to near space. However, methodological limitations in these studies, as well as our own results with a similar paradigm, challenge the validity of this claim. We aim to contribute to the crucial debate on the role of spatial distance on humans feeling of responsibility by providing a respectful though critical analysis of recent findings and offering recommendations for future research.

neuroscience↗

bioRxiv2025

Spatial distance and temporal attentional focus modulate voluntary action preparation and awareness

Peripersonal space (PPS)--the immediate space surrounding the body--modulates perception and motor control. However, its impact on how voluntary actions are initiated and subjectively experienced remains underexplored. Similarly, how directing attention to different phases of an action, such as intention formation versus execution, and anticipating outcomes of an action, modulates the neural readiness for movement, has yet to be fully examined. This study investigates whether spatial proximity, attentional focus, and anticipated action outcomes influence action preparation and action awareness, using a virtual reality adaptation of the Libet clock paradigm during EEG recordings. Neural results reveal that attentional focus and anticipated action outcomes modulate different phases of motor preparation, as indexed by the readiness potential (RP)--a gradual buildup of neural activity preceding voluntary movement. Focusing on decision timing (without subsequent action outcomes) enhances early RP amplitude and decreases the late RP slope, suggesting increased preparatory neural engagement during intention formation. In contrast, focusing on action execution leads to a steeper late RP slope, indicating later and faster motor activity buildup when attention is directed toward movement onset. Anticipating action outcomes increased late RP slope, which was accompanied by the temporal binding effect: when a tone followed the action, both decision and action estimates shifted toward it. Spatial proximity also modulates early RP slope, with a steeper buildup in near versus far space, suggesting facilitated motor preparation within PPS. It further enhances the late RP amplitude when participants focused on their intention to act. Behavioural results show that actions are perceived as occurring earlier when the clock is displayed near compared to far, indicating that PPS influences the temporal perception of action timing. Overall, these findings highlight the dynamic interplay among external spatial context and internal cognitive processes in shaping motor preparation and action awareness. Importantly, a temporal internal attentional focus on intention to act modulates early RP--traditionally considered an unconscious stage of neural readiness. These results contribute to a deeper understanding of how PPS and the locus of attention on specific action phases affect action preparation and awareness, with potential implications for future research on the sense of agency and voluntary action decision making.

neuroscience↗

bioRxiv2024

Three-dimensional chromatin mapping of sensory neurons reveals that cohesin-dependent genomic domains are required for axonal regeneration

The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression programme at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C and RNA-seq. We find that cohesin is required for the full induction of the regenerative transcriptional program, by organising 3D genomic domains required for the activation of regenerative genes. Importantly, loss of cohesin results in disruption of chromatin architecture at regenerative genes and severely impaired nerve regeneration. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent chromatin interactions in neuronal regeneration.

neuroscience↗

bioRxiv2023

The circadian clock is a pacemaker of the axonal regenerative ability

Peripheral nervous system injuries lead to long-term neurological disability due to limited axonal regenerative ability. Injury-dependent and -independent physiological mechanisms have provided important molecular insight into neuronal regeneration. However, whether common molecular denominators underpin both injury-dependent and independent biological processes remain unclear. Here, we performed a comparative analysis of recently generated transcriptomic datasets associated with the regenerative ability of sciatic dorsal root ganglia (DRG). Surprisingly, circadian rhythms were identified as a the most significantly enriched biological process associated with regenerative capability. We demonstrate that DRG neurons possess an endogenous circadian clock with a 24h oscillations of circadian genes and that their regenerative ability displays a diurnal oscillation in a mouse model of sciatic nerve injury. Consistently, transcriptomic analysis of DRG neurons showed a significant time-of-day dependent enrichment for processes associated with axonal regeneration, development and growth, as well as circadian associated genes, including the core clock genes Bmal1 and Clock. Indeed, DRG-specific ablation of the non-redundant clock gene Bmal1 showed that it is required for regenerative gene expression, neuronal intrinsic circadian regeneration and target reinnervation. Lastly, lithium, a chrono-active compound, enhanced nerve regeneration, in wildtype but not in Bmal1 and Cry1/2-deficient mice. Together, these data demonstrate that daily rhythms and the molecular clock fine-tune the regenerative response of DRG neurons, and that chrono-active drugs, such as lithium, are a novel potential approach to nerve repair.

neuroscience↗

bioRxiv2023

No evidence in favour of the existence of 'intentional' binding

Intentional binding refers to the subjective temporal compression between a voluntary action and its sensory outcome. Despite some studies having challenged the link between temporal compression and intentional action, the intentional binding is still widely used as an implicit measure for the sense of agency. The debate remains unsettled primarily because the experimental conditions used in previous studies were confounded with various alternative causes for temporal compression, and action intention has not yet been tested comprehensively against all potential alternative causes in a single study. Here, we solve this puzzle by jointly comparing participants estimates of the interval between three types of triggering events with comparable predictability - voluntary movement, passive movement, external sensory event - and an external sensory outcome (auditory or visual across experiments). Results failed to show intentional binding, i.e., no shorter interval estimation for the voluntary than the passive movement conditions. Instead, we observed temporal (but not intentional) binding when comparing both movement conditions to the external sensory condition. Thus, temporal binding seems to originate from sensory integration and temporal prediction, not from action intention. As such, these findings underscore the need to reconsider the use of "intentional binding" as a reliable proxy of the sense of agency. Public Significance StatementWhen we press a light switch and observe a bulb lightening, we experience a sense of agency, a feeling of control over these events. We also estimate the temporal interval between our voluntary action and its consequence shorter than the same interval between two events in which we are not involved. Such temporal binding has thus been taken as a measure of the sense of agency. However, our study reveals that voluntary actions are neither necessary, nor sufficient for temporal binding. Instead, temporal binding relies on predicting and integrating information. The sense of agency can be disturbed in various psychiatric disorders and its brain mechanisms are currently actively explored. Our study urges amending how it is measured.

neuroscience↗

bioRxiv2023

Changes in physicochemical properties and microbial community succession during leaf stacking fermentation

Leaf stacking fermentation involves enzymatic actions of many microorganisms and is an efficient and environmentally benign process for degrading macromolecular organic compounds. We investigated the dynamics of metabolite profiles, bacterial and fungal communities and their interactions during fermentation using cigar leaves from three geographic regions. The results showed that the contents of total sugar, reducing sugar, starch, cellulose, lignin, pectin, polyphenol and protein in cigar tobacco leaves was significantly decreased during fermentation. Notably, the furfural, neophytadiene, pyridine, benzyl alcohol, geranyl acetone, 2-butanone, 3-hydroxy-, N-hexanal, isoamylalcohol and 2,3-pentanedione were important features volatile aroma compounds during fermentation. The -diversity of fungi and bacteria initially increased and then decreased during fermentation. The microbial diversity was influenced by fermentation stages and growing locations, in which the fermentation stages had greater impacts on the microbial diversity than locations. Microbiome profiling had identified several core bacteria including Sphingomonas, Bacillus, Staphylococcus, Pseudomonas, Ralstonia, Massilia and Fibrobacter. Fungal biomarkers included Aspergillus, Penicillium, Fusarium, Cladosporium and Trichomonascus. Interestingly, the molecular ecological networks showed that the core taxa had significant correlations with metabolic enzymes and physicochemical properties; bacteria and fungi jointly participated in the carbohydrate and nitrogen compound degrading and volatile aroma compound chemosynthesis processes during fermentation. These studies provide insights into the coupling of material conversion and microbial community succession during leaf fermentation. IMPORTANCECigar tobacco leaves are still crude after air curing. Fermentation can eliminate the pungent and bitter taste of the leaves and promote the accumulations of aromatic compounds. Hitherto, there has been no systematic study on the material conversion, metabolic enzymes and microbial community changes and their interactions in fermented leaves. The significance of our research is in identifying the potential metabolic cooperation related to microbial community, which will greatly enhance our understanding of microorganism to convert macromolecular organic to small molecules during the leaf stacking fermentation process.

microbiology↗

bioRxiv2022

A Peronophythora litchii RXLR effector PlAvh202 enhances plant susceptibility by destabilizing host SAMS

Oomycete pathogens can secret hundreds of effectors into plant cells to interfere with plant immune system during infection. Here we identified a cytoplasmic RXLR effector from the most destructive pathogen of litchi, Peronophythora litchii, and named it as PlAvh202. PlAvh202 could suppress cell death triggered by INF1 and Avr3a/R3a in Nicotiana benthamiana, and was essential for P. litchii virulence. In addition, PlAvh202 also suppressed plant immune responses and promoted the susceptibility of N. benthamiana to Phytophthora capsici. Further research revealed that PlAvh202 could suppress ethylene (ET) production by targeting and destabilizing plant S-adenosyl-L-methionine synthetase (SAMS), a key enzyme in ET biosynthesis pathway, in a 26S proteasome-dependent manner. Transient expression of LcSAMS3 induced ET production and enhanced plant resistance, whereas inhibition of ET biosynthesis promoted P. litchii infection, supporting that LcSAMS and ET positively regulate litchi immunity towards P. litchii. Overall, these findings highlight that SAMS can be targeted by oomycete RXLR effector to manipulate ET-mediated plant immunity.

plant biology↗

bioRxiv2022

GLOBAL HOST RESPONSES TO THE MICROBIOTA AT SINGLE CELL RESOLUTION IN GNOTOBIOTIC ZEBRAFISH

Resident microbes are a feature of vertebrate animals that influence diverse aspects of their biology from tissue development to metabolism. Here we describe transcriptional responses to the microbiota across all the cells of a model developing vertebrate, the larval zebrafish. By performing single cell transcriptomic analysis of whole germ free and conventionalized larvae, we show that the impacts of the microbiota are sensed by all major organ systems but that responses are highly specific to different cell types. The presence of microbiota stimulates the expansion of progenitor-like cells in epithelial tissues and increases proliferation gene expression in progenitor-like cell populations of the immune and nervous systems. Across many cell types, including enterocytes, immune cells, and neurons, the microbiota upregulates expression of genes involved in microbial responses, cell type-specific activities, and cell type-specific deployment of ATP metabolism genes. These combined transcriptional patterns demonstrate how the microbiota simultaneously modulate cellular immune and metabolic programs. The impacts of the microbiota on tissue development are illustrated by the exocrine pancreas, which in the absence of the microbiota is smaller and composed of uniformly differentiated acinar cells. The presence of the microbiota results in exocrine pancreas enlargement and heterogeneous cellular expression of digestive enzyme and secretion genes, demonstrating how the microbiota promotes plasticity in tissue development and function. This single cell transcriptional dataset demonstrates the impacts of the microbiota on vertebrate development across the body and provides a foundation for dissecting cell type specific responses to microbial consortia members or molecules. SummaryAnimal development proceeds in the presence of intimate microbial associations, but the extent to which different host cells across the body respond to resident microbes remains to be fully explored. Using the vertebrate model organism, the larval zebrafish, we assessed transcriptional responses to the microbiota across the entire body at single cell resolution. We find that cell types across the body, not limited to tissues at host-microbe interfaces, respond to the microbiota. Responses are cell-type specific, but across many tissues the microbiota enhances cell proliferation, increases metabolism, and stimulates a diversity of cellular activities, revealing roles for the microbiota in promoting developmental plasticity. This work provides a resource for exploring transcriptional responses to the microbiota across all cell types of the vertebrate body and generating new hypotheses about the interactions between vertebrate hosts and their microbiota.

developmental biology↗

bioRxiv2022

Dual Targeting of FLT3 and LSD1 Disrupts the MYC Super-Enhancer Complex in Acute Myeloid Leukemia

Mutations in Fms-like tyrosine kinase 3 (FLT3) are common drivers in acute myeloid leukemia (AML) yet FLT3 inhibitors only provide modest clinical benefit. Prior work has shown that inhibitors of lysine-specific demethylase 1 (LSD1) enhance kinase inhibitor activity in AML. Here we show that combined LSD1 and FLT3 inhibition induces synergistic cell death in FLT3-mutant AML. Multi-omic profiling revealed that the drug combination disrupts STAT5, LSD1, and GFI1 binding at the MYC blood super-enhancer, suppressing super-enhancer activation as well as MYC expression and activity. The drug combination simultaneously results in the accumulation of repressive H3K9me1 methylation, an LSD1 substrate, at MYC target genes. We validated these findings in 72 primary AML samples with the nearly every sample demonstrating synergistic responses to the drug combination. Collectively, these studies provide preclinical rationale for the investigation of dual FLT3/LSD1 inhibition in a clinical trial.

cancer biology↗

bioRxiv2022

GoPeaks: Histone Modification Peak Calling for CUT&Tag

Genome-wide mapping of the histone modification landscape is critical to understanding tran-scriptional regulation. Cleavage Under Targets and Tagmentation (CUT&Tag) is a new method for profiling the localization of covalent histone modifications, offering improved sensitivity and decreased cost compared with Chromatin Immunoprecipitation Sequencing (ChIP-seq). Here, we present GoPeaks, a peak calling method specifically designed for histone modification CUT&Tag data. GoPeaks implements a Binomial distribution and stringent read count cut-off to nominate candidate genomic regions. We compared the performance of GoPeaks against commonly used peak calling algorithms to detect H3K4me3, H3K4me1, and H3K27Ac peaks from CUT&Tag data. These histone modifications display a range of peak profiles and are frequently used in epigenetic studies. We found GoPeaks robustly detects genome-wide histone modifications and, notably, identifies H3K27Ac with improved sensitivity compared to other standard peak calling algorithms.

bioinformatics↗

bioRxiv2021

FoQDE2-dependent milRNA promotes Fusarium oxysporum f. sp. cubense virulence by targeting a glycosyl hydrolase coding gene at transcriptional level

MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding gene expression primarily found in plants and animals. Fungi produce microRNA-like RNAs (milRNAs) that are structurally similar to miRNAs and functionally important in various biological processes. The fungus Fusarium oxysporum f. sp. cubense (Foc) is the causal agent of Panama disease that threatens global banana production. It remains uncharacterized about the biosynthesis and functions of milRNAs in Foc. In this study, we investigated the biological function of milRNAs contributing to Foc pathogenesis. Within 24 hours post infecting the host, the Argonaute coding gene FoQDE2, and two Dicer coding genes FoDCL1 and FoDCL2, all of which are involved in milRNA biosynthesis, were significantly induced. FoQDE2 deletion mutant exhibited decreased virulence and hypersensitivity to hydrogen peroxide (H2O2). These results indicate that milRNA biosynthesis is crucial for Foc pathogenesis. By small RNA sequencing, we identified 364 small RNA-producing loci in the Foc genome, 25 of which were significantly downregulated in the FoQDE2 deletion mutant, from which milR-87 was verified as a FoQDE2-depedent milRNA based on qRT-PCR analysis. Through deletion and overexpression of milR-87 in the wild-type Foc strain, functions of milR-87 were studied. The results showed that milR-87 is crucial for Foc virulence in infection process. We furthermore identified a glycosyl hydrolase-coding gene, FOIG_15013, as the direct target of milR-87. The FOIG_15013 deletion mutant displayed a dramatic increase in the growth, conidiation and virulence. Transient expression of FOIG_15013 in Nicotiana benthamiana leaves activates the host defense responses. Collectively, this study documents the involvement of milRNAs in the manifestation of the devastating fungal disease in banana, and demonstrates the importance of milRNAs in the pathogenesis and other biological processes. Further analyses of the biosynthesis and expression regulation of fungal milRNAs may offer a novel strategy to combat devastating fungal diseases. Author summaryThe fungus Fusarium oxysporum f. sp. cubense (Foc) is the causal agent of Panama disease that threatens global banana production. As a typical representative of F. oxysporum species complex, the pathogen has been widely concerned. However, pathogenesis of Foc is not fully elucidated. In particular, pathogenic regulatory mechanism of the microRNA like small RNAs (milRNAs) found in Foc is unknown. Here, we found that FoQDE2, one Argonaute coding gene, and two Dicer coding genes FoDCL1 and FoDCL2, which are involved in milRNA biosynthesis, are significantly induced during the early infection stage of Foc. The results suggested that the milRNAs biosynthesis mediated by these genes may play an active role in the infection process of Foc. Based on this assumption, we subsequently found a FoQDE2-dependent milRNA (milR-87) and identified its target gene. Functional analysis showed that FoQDE2, miR-87 and its target gene were involved in the pathogenicity of Foc in different degree. The studies help us gain insight into the pathogenesis with FoQDE2, milR-87, and its target gene as central axis in Foc. The identified pathogenicity-involved milRNA provides an active target for developing novel and efficient biocontrol agents against Panama disease.

microbiology↗

bioRxiv2021

Intergenerational effects of a paternal Western diet during adolescence on offspring gut microbiota, stress reactivity and social behavior

The global consumption of highly processed, calorie-dense foods has contributed to an epidemic of overweight and obesity, along with negative consequences for metabolic dysfunction and disease susceptibility. As it becomes apparent that overweight and obesity have ripple effects through generations, understanding of the processes involved is required, in both maternal and paternal epigenetic inheritance. We focused on the patrilineal effects of a Western-style high-fat (21%) and high-sugar (34%) diet (WD) compared to control diet (CD) during adolescence and investigated F0 and F1 mice for physiological and behavioral changes. F0 males (fathers) showed increased body weight, impaired glycemic control, and decreased attractiveness to females. Paternal WD caused significant phenotypic changes in F1 offspring, including higher body weights of pups, increased Actinobacteria abundance in the gut microbiota (ascertained using 16S microbiome profiling), a food preference for WD pellets, increased male dominance and attractiveness to females, as well as decreased behavioral despair. These results collectively demonstrate the long-term intergenerational effects of a Western-style diet during paternal adolescence. The behavioral and physiological alterations in F1 offspring provide evidence of adaptive paternal programming via epigenetic inheritance. These findings have important implications for understanding paternally mediated intergenerational inheritance, and its relevance to offspring health and disease susceptibility.

neuroscience↗

bioRxiv2021

Combinatorial small molecule-mediated activation of CBP/p300 with environmental enrichment in chronic severe experimental spinal cord injury to enable axon regeneration and sprouting for functional recovery

The interruption of spinal circuitry following spinal cord injury disrupts neural activity and is followed by a failure to mount an effective regenerative gene expression response resulting in permanent neurological disability. Functional recovery requires the enhancement of axonal and synaptic plasticity of spared as well as injured fibres, which need to sprout and/or regenerate to form new connections. Here we will investigate whether the combined epigenetic stimulation of the regenerative gene expression program with neuronal activity-dependent enhancement of neuroplasticity and guidance can overcome the current inability to promote neurological recovery in severe and chronic spinal cord injury. This will be carried out by delivering the small molecule CBP/p300 activator CSP-TTK21 in combination with environmental enrichment. We will deliver the CBP/p300 activator CSP-TTK21 weekly between week twelve and twenty following a severe transection model of spinal cord injury in the mouse. Data analysis will assess modifications in regenerative signalling, in motor and sensory axon sprouting and regeneration, in synaptic plasticity as well as in neurological sensorimotor recovery. This approach will advance our mechanistic understanding of regenerative failure and provide insight of whether combining growth promoting strategies with enhancement of neural activity is an effective therapeutic strategy in chronic spinal cord injury.

neuroscience↗

bioRxiv2021

Transsaccadic integration operates independently in different feature dimensions

Our knowledge about objects in our environment reflects an integration of current visual input with information from preceding gaze fixations. Such a mechanism may reduce uncertainty, but requires the visual system to determine which information obtained in different fixations should be combined or kept separate. To investigate the basis of this decision, we conducted three experiments. Participants viewed a stimulus in their peripheral vision, then made a saccade that shifted the object into the opposite hemifield. During the saccade, the object underwent changes of varying magnitude in two feature dimensions (Experiment 1: color and location, Experiments 2 and 3: color and orientation). Participants reported whether they detected any change and estimated one of the post-saccadic features. Integration of pre-saccadic with post-saccadic input was observed as a bias in estimates towards the pre-saccadic feature value. In all experiments, pre-saccadic bias weakened as the magnitude of the transsaccadic change in the estimated feature increased. Changes in the other feature, despite having a similar probability of detection, had no effect on integration. Results were quantitatively captured by an observer model where the decision whether to integrate information from sequential fixations is made independently for each feature and coupled to awareness of a feature change.

neuroscience↗

bioRxiv2019

Combinatorial proteomics and transcriptomics identify AMPK in the control of the axonal regeneration programme of DRG sensory neurons after spinal injury

Regeneration after injury occurs in axons that lie in the peripheral nervous system but it fails in the central nervous system limiting functional recovery. Despite recent progress, the signalling response to injury of peripheral versus central projecting axons that might underpin this differential regenerative ability is currently largely uncharacterized. To fill this knowledge gap, here we combined axoplasmic proteomics from peripheral sciatic or central projecting dorsal root axons from sciatic DRG neurons. Proteomics was combined with cell body RNAseq to compare axonal and soma responses between a spinal regeneration-incompetent versus sciatic regeneration-competent nerve injury. This allowed the identification of injury-dependent signalling pathways uniquely represented in peripheral versus central projecting sciatic DRG axons. RNAseq and proteomics analysis suggested AMPK as a putative regulator of axonal regenerative signalling pathways. AMPK immunoprecipitation followed by mass spectrometry from DRG suggested that the 26S proteasome and its regulatory subunit PSMC5 preferentially interact with AMPK for proteasomal degradation following sciatic axotomy. Mechanistically, we found that the proteasome and CaMKII-dependent proteasomal subunit PSMC5 regulates AMPK1 protein expression. Finally, conditional deletion of AMPK1 promoted multiple regenerative signalling pathways and robust axonal growth across the injured spinal cord, suggesting inhibition of AMPK as a novel regenerative target following spinal injury.\n\nHIGHLIGHTSO_LIAxoplasmic proteomics from sciatic or centrally projecting branches of sciatic DRG identifies unique protein enrichment and signalling pathways, including prior and subsequent to a spinal regeneration-incompetent versus sciatic regeneration-competent axonal injury\nC_LIO_LICombined axoplasmic DRG proteomics and cell body RNAseq analysis suggest AMPK as a central regulator controlling axonal regeneration\nC_LIO_LIThe 26S proteasome and the 19S regulatory subunit PSMC5 interact with AMPK following sciatic axotomy. PSMC5 regulates AMPK1 protein levels\nC_LIO_LIAMPK1 conditional deletion enhances robust axonal growth following SCI\nC_LI

neuroscience↗

bioRxiv2018

PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure

The molecular mechanisms discriminating between regenerative failure and success remain elusive. While a regeneration-competent peripheral nerve injury mounts a regenerative gene expression response in bipolar dorsal root ganglia (DRG) sensory neurons, a regeneration-incompetent central spinal cord injury does not. This dichotomic response offers a unique opportunity to investigate the fundamental biological mechanisms underpinning regenerative ability. Following a pharmacological screen with small molecule inhibitors targeting key epigenetic enzymes in DRG neurons we identified HDAC3 signalling as a novel candidate brake to axonal regenerative growth. In vivo, we determined that only a regenerative peripheral but not a central spinal injury induces an increase in calcium, which activates protein phosphatase 4 that in turn dephosphorylates HDAC3 thus impairing its activity and enhancing histone acetylation. Bioinformatics analysis of ex vivo H3K9ac ChIPseq and RNAseq from DRG followed by promoter acetylation and protein expression studies implicated HDAC3 in the regulation of multiple regenerative pathways. Finally, genetic or pharmacological HDAC3 inhibition overcame regenerative failure of sensory axons following spinal cord injury. Together, these data indicate that PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC=\"FIGDIR/small/446963_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (40K):\norg.highwire.dtl.DTLVardef@1bd577corg.highwire.dtl.DTLVardef@1ba990aorg.highwire.dtl.DTLVardef@195813corg.highwire.dtl.DTLVardef@57abc7_HPS_FORMAT_FIGEXP M_FIG Graphical AbstractFollowing central nervous system (CNS) spinal injury, protein phosphatase 4/2 activity is not induced since calcium levels remain unchanged compared to uninjured conditions. HDAC3 remains phosphorylated and occupies deacetylated chromatin contributing to its compaction inhibiting gene expression. Following peripheral nervous system (PNS) sciatic injury, protein phosphatase 4/2 activity is induced by calcium. HDAC3 is dephosphorylated leading to its inhibition and release from chromatin sites contributing to increase in histone acetylation and in the expression of regeneration associated genes (RAGs).\n\nC_FIG

neuroscience↗

bioRxiv2017

How Does Mixed Reality Affect Quiet Stance?

Mixed reality (MR) has promise for learning, design, and entertainment, and for use during everyday life. However, when interacting with objects in mixed reality, will moving objects make us fall or perturb our postural stability? To address this question, we recruited participants, instructed them to stand quietly, and measured how much virtual objects presented in mixed reality (Microsoft HoloLens) affected their stance. We analyzed the effects of solid object and text, in both a static and a dynamic setting. Mixed reality events induced some movements, but the effect, while significant, was exceptionally small (< 1mm & < 0.5{degrees} perturbations in terms of mean distance and angle rotations). We conclude that induced movement in \"real reality\" should not be too much of a concern when designing mixed reality applications.

physiology↗