Biology subjects

Fu, M.

Publications and source records attributed to Fu, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Activity-dependent Sonic hedgehog signaling promotes astrocyte modulation of synaptic plasticity

The influence of neural activity on astrocytes and their reciprocal interactions with neurons has emerged as an important modulator of synapse function. Astrocytes exhibit activity-dependent changes in gene expression, yet the molecular mechanisms by which they accomplish this have remained largely unknown. The molecular signaling pathway, Sonic hedgehog (Shh), mediates neuron-astrocyte communication and regulates the organization of cortical synapses. Here, we demonstrate that neural activity stimulates Shh signaling in cortical astrocytes and upregulates expression of Hevin and SPARC, astrocyte derived molecules that modify synapses. Whisker stimulation and chemogenetic activation both increase Shh activity in deep layers of the somatosensory cortex, where neuron-astrocyte Shh signaling is predominantly found. Experience-dependent Hevin and SPARC require intact Shh signaling and selective loss of pathway activity in astrocytes occludes experience-dependent structural plasticity. Taken together, these data identify Shh signaling as an activity-dependent, neuronal derived cue that stimulates astrocyte interactions with synapses and promotes synaptic plasticity.

neuroscience↗

bioRxiv2024

Granzyme B-based CAR T cells block metastasis by eliminating circulating tumor cells

Chimeric antigen receptor (CAR) T cells have limited efficacy against solid tumors due to the hostile microenvironment. Circulating tumor cells (CTCs) are essential to metastasis, which is the cause of most of cancer-related death. Here, we generated GrB-CAR T cells targeting membrane-bound HSP70 (mHSP70), a highly tumor-specific antigen detected in numerous cancers. GrB-CAR T cells exhibited potent cytotoxicity against a broad spectrum of cancer cell lines and stem-like cancer cells in vitro and effectively inhibited xenograft tumor growth in vivo. Importantly, GrB-CAR T cells markedly decreased the number of CTCs and, therefore, hindered cancer metastasis in spontaneous metastasis models with uncontrollable primary tumor growth, a scenario commonly encountered in clinical trials of CAR T therapies for solid tumors. Furthermore, despite the 100% homology between human and macaque HSP70 protein, the autotransplantation of macaque T cells expressing human GrB-CAR did not cause any obvious toxic effects. These results not only demonstrate GrB-CAR T cells as a safe and effective tactic with broad-spectrum anticancer activity, but also offer strong experimental evidence and proof-of-concept validation for CAR T cell-mediated metastasis inhibition by targeting CTCs.

immunology↗

bioRxiv2023

Towards establishing a rapid constant temperature detection method for canine parvovirus based on endonuclease activities

Canine parvovirus can cause a high morbidity and mortality rate in puppies, posing a significant threat to both pet dogs and the breeding industry. Rapid, accurate and convenient detection methods are important for the early intervention and treatment of canine parvovirus. In this study, we propose a visual CPV detection system called nucleic acid mismatch enzyme digestion (NMED). This system combines reverse transcription-loop mediated isothermal amplification (RT-LAMP), endonuclease for gene mismatch detection and colloidal gold lateral chromatography. We demonstrated that NMED can induce the binding of the amplicon from the sample to the specific labeling probe, which in turn triggers digestion by the endonuclease. The sensitivity and visual visibility of RT-LAMP were increased by combining of endonuclease and colloidal gold lateral chromatography assisted by a simple temperature-controlled device. The sensitivity of the NMED assay was 1 copy/L, which was consistent with qPCR. The method was validated with 10 clinical samples that potentially had CPV infection and achieved 100% accuracy. As a rapid, accurate and convenient molecular diagnostic method, NMED has great potential for application in the field of pathogenic microorganism detection.

molecular biology↗

bioRxiv2023

Increased intrinsic membrane excitability is associated with hypertrophic olivary degeneration in spinocerebellar ataxia type 1

One of the characteristic areas of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key role in motor learning. In addition to its vulnerability in SCAs, the IO is also susceptible to a distinct pathology known as hypertrophic olivary degeneration (HOD). Clinically, HOD has been exclusively observed after lesions in the brainstem disrupt inhibitory afferents to the IO. Here, for the first time, we describe HOD in another context: spinocerebellar ataxia type 1 (SCA1). Using the genetically-precise SCA1 knock-in mouse model (SCA1-KI; both sexes used), we assessed SCA1-associated changes in IO neuron structure and function. Concurrent with degeneration, we found that SCA1-KI IO neurons are hypertrophic, exhibiting early dendrite lengthening and later somatic expansion. Unlike in previous descriptions of HOD, we observed no clear loss of IO inhibitory innervation; nevertheless, patch-clamp recordings from brainstem slices reveal that SCA1-KI IO neurons are hyperexcitable. Rather than synaptic disinhibition, we identify increases in intrinsic membrane excitability as the more likely mechanism underlying this novel SCA1 phenotype. Specifically, transcriptome analysis indicates that SCA1-KI IO hyperexcitability is associated with a reduced medullary expression of ion channels responsible for spike afterhyperpolarization (AHP) in IO neurons - a result that has a functional consequence, as SCA1-KI IO neuron spikes exhibit a diminished AHP. These results reveal membrane excitability as a potential link between disparate causes of IO degeneration, suggesting that HOD can result from any cause, intrinsic or extrinsic, that increases excitability of the IO neuron membrane. Significance statementLittle is known about the factors that make inferior olive (IO) neurons susceptible to degeneration in the spinocerebellar ataxias (SCAs), a group of inherited neurodegenerative movement disorders. Another well-described form of IO degeneration, known as hypertrophic olivary degeneration (HOD), results from inhibitory denervation of the IO after brainstem injury. Here, we describe a novel finding of HOD in SCA1 without inhibitory denervation, in association with increased intrinsic membrane excitability and reduced potassium channel transcripts. This suggests that increased membrane excitability may be the underlying primary mechanism of HOD. Identifying hyperexcitability as the mechanistic driver of HOD would imply that reducing intrinsic IO excitability could be an effective strategy for treating diverse causes of both inherited and sporadic olivary degeneration.

neuroscience↗

bioRxiv2022

The right inferior frontal gyrus as pivotal node and effective regulator of the basal ganglia-thalamocortical response inhibition circuit in humans

The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in the last few decades. However, the pivotal brain nodes and directed casual regulation within this inhibitory circuit in humans remains controversial. Here, we capitalize on recent progress in robust and biologically plausible directed causal modelling (DCM-PEB) and a large fMRI response inhibition dataset (n=218) to determine key nodes, their causal regulation and modulation via biological variables (sex) and inhibitory performance in the inhibitory control circuit encompassing the right inferior frontal gyrus (rIFG), caudate nucleus (rCau), globus pallidum (rGP) and thalamus (rThal).The entire neural circuit exhibited high intrinsic connectivity and an increasing rIFG inflow and its causal regulation over the rCau and rThal during response inhibition. In addition, sex and behavioral performance influenced the architecture of the regulatory circuits such that women displayed increased rThal self-inhibition and decreased rThal to GP modulation, while better inhibitory performance was associated with stronger rThal to rIFG communication. Furthermore, control analyses did not reveal a similar key communication in a left lateralized model. Together these findings indicate a pivotal role of the rIFG as input and causal regulator of subcortical response inhibition nodes.

neuroscience↗

bioRxiv2022

Opposing associations of Internet Use Disorder symptom domains with structural and functional organization of the striatum: a dimensional neuroimaging approach

BackgroundAccumulating evidence suggests brain structural and functional alterations in Internet Use Disorder (IUD). However, conclusions are strongly limited due to the retrospective case-control design of the studies, small samples, and the focus on general rather than symptom-specific approaches. MethodsWe here employed a dimensional multi-methodical MRI-neuroimaging design in a final sample of n = 203 subjects to examine associations between levels of IUD and its symptom-dimensions (loss of control/time management, craving/social problems) with brain structure, resting state and task-based (pain empathy, affective go/no-go) brain function. ResultsAlthough the present sample covered the entire range of IUD, including normal, problematic as well as pathological levels, general IUD symptom load was not associated with brain structural or functional alterations. However, the symptom-dimensions exhibited opposing associations with the intrinsic and structural organization of the brain, such that loss of control/time management exhibited negative associations with intrinsic striatal networks and hippocampal volume, while craving/social problems exhibited a positive association with intrinsic striatal networks and caudate volume. ConclusionsOur findings provided the first evidence for IUD symptom-domain specific associations with progressive alterations in the intrinsic structural and functional organization of the brain, particularly of striatal systems involved in reward, habitual and cognitive control processes.

neuroscience↗

bioRxiv2021

E3 ligase TRIM47 positively regulates endothelial activation and pulmonary inflammation through potentiating the K63-linked ubiquitination

Endothelial activation plays an essential role in the pathology of sepsis-induced acute lung injury, but the detailed regulatory mechanisms remain largely unknown. Here, we demonstrated that TRIM47, an ubiquitin E3 ligase of tripartite protein family, is highly expressed in vascular endothelial cells and is up-regulated during TNF-induced endothelial activation. Knockdown of TRIM47 in endothelial cells prevents the transcription of multiple pro-inflammatory cytokines, reduces monocyte adhesion and the expression of adhesion molecules, and inhibits the secretion of IL-1{beta} and IL-6 into the supernatant. By contrast, overexpression of TRIM47 promotes inflammatory response and monocyte adhesion upon TNF stimulation. TRIM47 modulates the activation of NF-{kappa}B and MAPK signaling pathways during endothelial activation. Further experiment confirmed that TRIM47 interacts with TRAF2 and mediates K63-linked ubiquitination. In addition, TRIM47-deficient mice are more resistant to lipopolysaccharide-induced acute lung injury and death, due to attenuated pulmonary inflammation. Taken together, our studies suggest that TRIM47 promotes pulmonary inflammation and injury at least partly through potentiating the K63-linked ubiquitination of TRAF2, which in turn activates NF-{kappa}B and MAPK signaling pathways to trigger inflammatory response in endothelial cells.

cell biology↗

bioRxiv2021

Asymmetric Redundancy of Soybean Nodule Inception (NIN) Genes in Root Nodule Symbiosis

NIN is one of the most important root nodule symbiotic genes as it is required for both infection and nodule organogenesis in legume. Unlike most legumes with a sole NIN gene, there are four putative NIN genes in soybean (Glycine max). Whether and how these orthologs NIN genes contribute to soybean-rhizobia symbiotic interaction remain unknown. In this study, we found that all four GmNIN genes are induced by rhizobia, and that conserved CE and CYC binding motifs in their promoter regions are required for their expression in the nodule formation process. By generation of multiplex Gmnin mutants, we found that Gmnin1a nin2a nin2b triple mutant and Gmnin1a nin1b nin2a nin2b quadruple mutant displayed similar defects in rhizobia infection and root nodule formation, Gmnin2a nin2b produced less nodules but displayed hyper infection phenotype than wild type, while a Gmnin1a nin1b double mutant nodulated as wild type. Overexpression of GmNIN1a, GmNIN1b, GmNIN2a, and GmNIN2b reduced nodule numbers after rhizobia inoculation, with GmNIN1b overexpression having the weakest effect. In addition, overexpression of GmNIN1a, GmNIN2a, or GmNIN2b, but not GmNIN1b, produced malformed pseudo-nodule like structures without rhizobia inoculation. In conclusion, GmNIN1a, GmNIN2a and GmNIN2b play functionally redundant yet complicated roles for soybean nodulation. GmNIN1b, although is expressed at comparable level with other homologs, plays a minor role in root nodule symbiosis. Our work provides insight into the understanding of asymmetrically redundant function of GmNIN genes in soybean.

developmental biology↗

bioRxiv2021

The mirror neuron system compensates for amygdala dysfunction-associated social deficits in individuals with higher autistic traits

The amygdala is a core node in the social brain which exhibits structural and functional abnormalities in Autism spectrum disorder and there is evidence that the mirror neuron system (MNS) can functionally compensate for impaired emotion processing following amygdala lesions. In the current study, we employed an fMRI paradigm in 241 subjects investigating MNS and amygdala responses to observation, imagination and imitation of dynamic facial expressions and whether these differed in individuals with higher as opposed to lower autistic traits. Results indicated that individuals with higher compared to lower autistic traits showed reduced left amygdala responses to imitation and enhanced responses in the left superior temporal sulcus (STS) of the MNS to observation, imagination and imitation. Additionally, functional connectivity between the left amygdala and the left STS as well as some other MNS regions was increased in individuals with higher autistic traits, especially during imitation of fearful expressions. The amygdala-MNS connectivity significantly moderated autistic group differences on recognition memory for fearful faces and real-life social network indices, indicating that increased amygdala-MNS connectivity could diminish the social behavioral differences between higher and lower autistic trait groups. Overall, findings demonstrate decreased imitation-related amygdala activity in individuals with higher autistic traits in the context of increased cortical MNS activity and amygdala-MNS connectivity which may functionally compensate for amygdala dysfunction and social deficits. Training targeting the MNS may capitalize on this compensatory mechanism for therapeutic benefits in Autism spectrum disorder.

neuroscience↗

bioRxiv2021

Direct activation of endothelial cells by SARS-CoV-2 nucleocapsid protein is blocked by Simvastatin

Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the SARS-CoV-2 viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved with endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through TLR2/NF-{kappa}B and MAPK signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkablely, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, MERS-CoV, HUB1-CoV and influenza virus H1N1 did not affect endothelial activation. These findings are well consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy, and suggests that simvastatin, an FDA-approved lipid-lowering drug, may benefit to prevent the pathogenesis and improve the outcome of COVID-19 patients.

immunology↗

bioRxiv2021

A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration

The dramatically expanding COVID-19 needs multiple effective countermeasures. Neutralizing antibodies are a potential therapeutic strategy for treating COVID-19. A number of neutralizing nanobodies (Nbs) were reported for their in vitro activities. However, in vivo protection of these nanobodies was not reported in animal models. In the current report, we characterized several RBD-specific Nbs isolated from a screen of an Nb library derived from an alpaca immunized with SARS-CoV-2 spike glycoprotein (S); among them, three Nbs exhibited picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and 15 circulating SARS-CoV-2 variants. To improve the efficacy, various configurations of Nbs were engineered. Nb15-NbH-Nb15, a novel trimer constituted of three Nbs, was constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15 exhibited sub-ng/ml neutralization potency against the wild-type and currently circulating variants of SARS-CoV-2 with a long half-life in vivo. In addition, we showed that intranasal administration of Nb15-NbH-Nb15 provided 100% protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15 is a potential candidate for both prevention and treatment of SARS-CoV-2 through respiratory administration. One sentence summaryNb15-NbH-Nb15, with a novel heterotrimeric bispecific configuration, exhibited potent and broad neutralization potency against SARS-CoV-2 in vitro and provided in vivo protection against SARS-CoV-2 infection in hACE2 transgenic mice via intranasal delivery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/429275v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@a30bc8org.highwire.dtl.DTLVardef@5a872eorg.highwire.dtl.DTLVardef@1610f74org.highwire.dtl.DTLVardef@13d9bd8_HPS_FORMAT_FIGEXP M_FIG Graphical abstract: C_FIG HighlightsO_LIWe described a novel heterotrimeric configuration of Nb-NbH-Nb (Nb15-NbH-Nb15) that exhibited improved viral inhibition and stability. C_LIO_LINb15-NbH-Nb15 provides ultrahigh neutralization potency against SARS-CoV-2 wild type and 18 mutant variants, including the current circulating variants of D614G and N501Y predominantly in the UK and South Africa. C_LIO_LIIt is the first to demonstrate the Nbs efficacy in preventing and treating SARS-CoV-2 infection in hACE2 transgenic mice via intranasal delivery. C_LI

microbiology↗

bioRxiv2020

Segregating domain-general from emotional context-specific inhibitory control systems - ventral striatum and orbitofrontal cortex serve as emotion-cognition integration hubs

Inhibitory control hierarchically regulates cognitive and emotional systems in the service of adaptive goal-directed behavior across changing task demands and environments. While previous studies convergently determined the contribution of prefrontal-striatal systems to general inhibitory control, findings on the specific circuits that mediate the context-specific impact of inhibitory control remained inconclusive. Against this background we employed an evaluated emotional Go/No Go task with fMRI in a large cohort of subjects (N = 250) to segregate brain systems and circuits that mediate domain-general from emotion-specific inhibition control. Particularly during a positive emotional context, behavioral results showed a lower accuracy for No Go trials and a faster response time for Go trials. While the dorsal striatum and lateral frontal regions were involved in inhibitory control irrespective of emotional context, activity in the ventral striatum (VS) and medial orbitofrontal cortex (mOFC) varied as a function of emotional context. On the voxel-wise network level, limbic and striatal systems generally exhibited highest changes in global brain connectivity during inhibitory control, while global brain connectivity of the left mOFC was less suppressed during emotional contexts. Functional connectivity analyses moreover revealed that negative coupling between the VS with inferior frontal gyrus (IFG)/insula and mOFC varied as a function of emotional context. Together these findings indicated separable domain general systems as well emotional context-specific inhibitory brain systems which specifically encompass the VS and its connections with frontal regions.

neuroscience↗

bioRxiv2020

The genomic and transcriptomic foundations of viviparous seed development in mangroves

Vivipary in plants refers to a specific seed development and reproductive strategy where seeds minimize the dormancy stage and germinate while still attached to their maternal plants. It is one of the most unique adaptive genetic features used by many mangrove species where elongated hypocotyls aid in quick root emergence to anchor the seedling in coastal intertidal wetlands. The genetic mechanisms behind mangrove vivipary, however, remain elusive. Using comparative genomic and transcriptomic technologies to investigate viviparous mangroves and their close inland relatives, we found that a full array of gene expression profiles were altered, including key plant hormone metabolic pathways, high expression of embryonic signature genes, and reduced production of proanthocyanidins and storage proteins. Along with these changes, a major gene regulating seed dormancy, Delay of Germination-1 (DOG1), is entirely missing or defunct within the entire linage of the four genera with true viviparous characteristics. These results suggest a systemic level change is required to warrant the genetic program of mangrove vivipary. Understanding of the molecular processes of vivipary could benefit the design of pregerminated propagules for forestation in harsh environments or prevent precocious germination of grain crops pre- and post-harvest.

genomics↗

bioRxiv2020

Role of Mcpip1 in obesity-induced hepatic steatosis as determined by myeloid and liver-specific conditional knockouts.

Monocyte chemoattractant protein-induced protein 1 (MCPIP1, alias Regnase1) is a negative regulator of inflammation, acting through cleavage of transcripts coding for proinflammatory cytokines and by inhibition of NF{kappa}B activity. Moreover, it was demonstrated, that MCPIP1 regulates lipid metabolism both in adipose tissue and hepatocytes. In this study, we investigated the effects of tissue-specific Mcpip1 deletion on the regulation of hepatic metabolism and development of non-alcoholic fatty liver disease (NAFLD). We used knock-in control Mcpip1fl/fl mice and animals with deletion of Mcpip1 in myeloid leukocytes (Mcpip1fl/flLysMCre) and in hepatocytes (Mcpip1fl/flAlbCre), which were fed chow or a high-fat diet (HFD) for 12 weeks. Mcpip1fl/flLysMCre mice were fed a chow diet were characterized by a significantly reduced hepatic expression of genes regulating lipid and glucose metabolism, which subsequently resulted in hypoglycemia and dyslipidemia. These animals also displayed systemic inflammation, demonstrated by increased concentrations of cytokines in the plasma. On the other hand, there were no significant changes in phenotype in Mcpip1fl/flAlbCre mice. Although we detected a reduced hepatic expression of genes regulating glucose metabolism and {beta}-oxidation in these mice, they remained asymptomatic. Upon feeding them a HFD, Mcpip1fl/flLysMCre mice did not develop obesity, glucose intolerance, nor hepatic steatosis, but were characterized by hypoglycemia and dyslipidemia, along with proinflammatory phenotype with symptoms of cachexia. Mcpip1fl/flAlbCre animals, following a HFD, became hypercholesterolemic, but accumulated lipids in the liver at the same level as Mcpip1fl/fl mice, and no changes in the level of soluble factors tested in the plasma were detected. In conclusion, we have demonstrated that Mcpip1 protein plays an important role in the liver homeostasis. Depletion of Mcpip1 in myeloid leukocytes, followed by systemic inflammation, has a more pronounced effect on controlling liver metabolism and homeostasis than the depletion of Mcpip1 in hepatocytes.

molecular biology↗

bioRxiv2020

Deletion of Mcpip1 in Mcpip1AlbKO mice recapitulates the phenotype of human primary biliary cholangitis

Background & AimsPrimary biliary cholangitis (PBC) is an autoimmune disease characterized by progressive destruction of the intrahepatic bile ducts. The immunopathology of PBC involves excessive inflammation; therefore, negative regulators of inflammatory response, such as Monocyte Chemoattractant Protein-1-Induced Protein-1 (MCPIP1, alias Regnase1) may play important roles in the development of PBC. The aim of this work was to verify whether Mcpip1 expression protects against development of PBC. MethodsGenetic deletion of Zc3h12a was used to characterize the role of Mcpip1 in the pathogenesis of PBC. 6-52-week-old Mcpip1fl/fl and Mcpip1AlbKO mice were used for immunohistochemical, biochemical and molecular tests. ResultsWe found that Mcpip1 deficiency in the liver recapitulates most of the features of human PBC, in contrast to mice with Mcpip1 deficiency in myeloid cells (Mcpip1LysMKO mice), which present with robust myeloid cell-driven systemic inflammation. In Mcpip1AlbKO livers, intrahepatic bile ducts displayed proliferative changes with inflammatory infiltration, bile duct destruction, and fibrosis leading to cholestasis. In plasma, increased concentrations of IgG, IgM, and AMA autoantibodies (anti-PDC-E2) were detected. Interestingly, the phenotype of Mcpip1AlbKO mice was robust in 6-week-old and 52-week-old mice, but milder in 12-24-week-old mice, suggesting early prenatal origin of the phenotype and age-dependent progression of the disease. Hepatic transcriptome analysis of 6-week-old and 24-week-old Mcpip1AlbKO mice showed 812 and 8 differentially expressed genes (DEGs), respectively, compared with age-matched control mice, and revealed a distinct set of genes compared to those previously associated with development of PBC. ConclusionsThe phenotype of Mcpip1AlbKO mice recapitulates most of the features of human PBC, and demonstrates early prenatal origin and age-dependent progression of PBC. Therefore, Mcpip1AlbKO mice provide a unique model for the study of PBC. Lay summaryDeletion of hepatic Mcpip1 in Mcpip1AlbKO mice leads to development of PBC that recapitulates phenotype of human patients. These animals, show early prenatal origin and age-dependent progression of the disease. Thus, Mcpip1AlbKO mice provide a unique model for studying PBC.

pathology↗

bioRxiv2020

Medial prefrontal activity at encoding determines recognition of threatening faces after 1.5 years

Studies demonstrated that faces with threatening emotional expressions are better remembered than non-threatening faces. However, whether this memory advantage persists over years and which neural systems underlie such an effect remains unknown. Here, we investigated recognition of incidentally encoded faces with angry, fearful, happy, sad and neutral expressions over >1.5 years (N= 89). Univariate analyses showed that threatening faces (angry, fearful) were better recognized than happy and neutral faces after >1.5 years, and that the threat-related memory enhancement was driven by forgetting of non-threatening faces. Multivariate principal component analysis (PCA) confirmed the discriminative performance between threatening and non-threatening faces. With an innovative Behavioral Pattern Similarity Analysis (BPSA) approach and functional magnetic resonance imaging (fMRI) acquisition during encoding, we further found that the long-term memory advantage for threatening faces were underpinned by differential neural encoding in the left inferior occipital gyrus (IOG) and right ventromedial prefrontal/orbitofrontal cortex (vmPFC/OFC). Our study provides the first evidence that threatening facial expressions lead to persistent face recognition over periods of >1.5 years and differential encoding-related activity in the visual cortex and medial prefrontal cortex may underlie this effect.

neuroscience↗

bioRxiv2020

Recombinant Protein IGF1-24 Stimulates Rat Cardiomyocytes Proliferation and Repairs Myocardial Injury

Mammal cardiomyocytes lose their ability of regeneration shortly after birth. Reduced cardiomyocytes number caused by myocardial damage is unable to reverse in current clinical therapies. Therefore, it is important and urgent to find new approaches to stimulate cardiomyocytes regeneration. Here we design a recombinant protein IGF1-24 and show that it triggers cardiomyocytes proliferation in rat. 7 days after tail intravenous injection of IGF1-24, 6-7-weeks-old healthy rats showed marked improvements in cardiomyocytes proliferation. Next, we injured rats cardiac with isoproterenol and treated them with IGF1-24 injection. We found that it efficiently induced cell proliferation with significant improvements in heart histology. These results show that the recombinant IGF1-24 stimulates cardiomyocytes proliferation and can be used to achieve cardiac repair through stimulating endogenous cardiomyocyte proliferation in rats. The IGF 1-24 could be a prospective medicine to heart repair because it has high efficiency in triggering cell proliferation and it can be easily applied to heart by intravenous injection

developmental biology↗

bioRxiv2020

Emotional contagion of pain across different social cues shares common and process-specific neural representations

Insular and anterior cingulate cortex activation across vicarious pain induction procedures suggests that they are core pain empathy nodes. However, pain empathic responses encompass emotional contagion as well as unspecific arousal and overlapping functional activations are not sufficient to determine shared and process-specific neural representations. We employed multivariate pattern analyses to fMRI data acquired during physical and affective vicarious pain induction and found spatially and functionally similar cross-modality (physical versus affective) whole-brain vicarious pain-predictive patterns. Further analyses consistently identified shared neural representations in the bilateral mid-insula. Mid-insula vicarious pain patterns were not sensitive to capture non-painful arousing negative stimuli but predicted self-experienced pain during thermal stimulation, suggesting process-specific representation of emotional contagion for pain. Finally, a domain-general vicarious pain pattern which predicted vicarious as well as self-experienced pain was developed. Our findings demonstrate a generalizable neural expression of vicarious pain and suggest that the mid-insula encodes emotional contagion for pain.

neuroscience↗