Biology subjects

Zeng, N.

Publications and source records attributed to Zeng, N..

9 recordsLinked to original sources

bioRxiv2026

The central amygdala integrates exogenous glucagon-like peptide 1 signals

Nuclei within the limbic system like the central amygdala (CeA) play a critical role in mediating fear, motivation, reward, and appetitive behavior. Although previous reports demonstrate the presence of the glucagon-like peptide-1 receptor (GLP-1R) in limbic nuclei, how limbic neurons mediate the actions of systemically administrated GLP-1R agonists is unclear. In this study, we investigated the CeAs response to peripherally administered GLP-1R agonist Exendin-4 (Ex-4) in vivo, and determined the functional requirement of select CeA neuron populations in acute Ex-4 induced hypophagia. Using fiber photometry, we observed that Ex-4 promoted a rapid and lasting activation of CeA neurons that was blocked by pretreatment with the GLP-1R antagonist Exendin-9. We then tested the functional requirement of CeA neuron activation in mediating Ex-4 induced hypophagia of standard grain chow using inhibitory chemogenetics. Chemogenetic inhibition of all CeA neurons significantly suppressed the hypophagic actions of Ex-4. Then using selective mouse Cre-drivers, we found that chemogenetic inhibition of protein kinase c delta (Prk-cd CeA) and GLP-1R (Glp1r CeA), but not somatostatin (SstCeA), neurons also attenuates the full hypophagic effect of Ex-4. Having observed that inhibition of Glp1rCeA modestly attenuated Ex-4 induced hypophagia of standard chow, we then tested whether these neurons might mediate Ex-4 suppression of energy-dense, palatable diet. We used intermittent high-fat diet (HFD) access and found that inhibition of Glp1rCeA neurons significantly rescued the reduction of HFD consumption by Ex-4. Collectively, these data demonstrate that the CeA responds to peripherally administered GLP-1R agonists and that multiple CeA neuron mediate GLP-1R agonist-mediated hypophagia.

neuroscience↗

bioRxiv2024

Stable, chronic in-vivo recordings from a fully wireless subdural-contained 65,536-electrode brain-computer interface device

Minimally invasive, high-bandwidth brain-computer-interface (BCI) devices can revolutionize human applications. With orders-of-magnitude improvements in volumetric efficiency over other BCI technologies, we developed a 50-m-thick, mechanically flexible micro-electrocorticography (ECoG) BCI, integrating a 256x256 array of electrodes, signal processing, data telemetry, and wireless powering on a single complementary metal-oxide-semiconductor (CMOS) substrate containing 65,536 recording channels, from which we can simultaneously record a selectable subset of up to 1024 channels at a given time. Fully implanted below the dura, our chip is wirelessly powered, communicating bi-directionally with an external relay station outside the body. We demonstrated chronic, reliable recordings for up to two weeks in pigs and up to two months in behaving non-human primates from somatosensory, motor, and visual cortices, decoding brain signals at high spatiotemporal resolution.

neuroscience↗

bioRxiv2021

DJ-1 depletion slows down immunoaging in T-cell compartments

Decline in immune function during aging increases susceptibility to different aging related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naive/memory T-cell subpopulations, still remain largely elusive. Here we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinsons disease (PD), unexpectedly delayed immunoaging in both human and mice. Compared with two gender-matched unaffected sibling carriers of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled frequencies of non-senescent T cells. The observation of a younger immune system in the index patient was further consolidated by the results in aged DJ-1 knockout mice. Our data from bone marrow chimera models and adoptive transfer experiments demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naive-CD8-intrinsic mechanisms. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.

immunology↗

bioRxiv2020

FAM13A regulates maturation and effector functions of natural killer cells

The polymorphism of the gene FAM13A (family with sequence similarity 13, member A) is strongly linked to the risk of lung cancer and chronic obstructive pulmonary disease, which are among the leading causes of mortality and morbidity in lung-related diseases worldwide. However, the underlying molecular and cellular mechanisms through which FAM13A contributes to the pathogenesis of these diseases largely remain unclear. Here, using a Fam13a knock out (KO) mouse model, we showed that Fam13a depletion upregulated the expression of the terminal differentiation and inhibitory marker, KLRG1 (killer cell lectin-like receptor G1) in natural killer (NK) cells. NK cells from Fam13a-deficient mice showed impaired IFN-{gamma} production either against target tumor cells or following various cytokine cocktail stimulations. Furthermore, the number of lung metastases induced by B16F10 melanoma cells was increased in Fam13a-KO mice. Collectively, our data suggest a key role of FAM13A in regulating NK cell functions, indicating that the key lung-disease risk gene FAM13A might contribute to the pathogenesis of several lung diseases via regulating NK cells.

immunology↗

bioRxiv2020

Chronic Exposure to Palmitic Acid Downregulates AKT in Beta-Cells through Activation of mTOR

High circulating lipids occurring in obese individuals and insulin resistant patients are considered a contributing factor to Type 2 Diabetes (T2D). Exposure to high lipids initially causes the beta-cells to expand in population. Long-term exposure to high lipids however is associated with failure of beta-cells and the development of T2D. To prevent the failure of beta-cells and development of Type 2 Diabetes, this study focuses on understanding the molecular mechanisms that underlie this biphasic response of beta-cells to lipid exposure. Using palmitic acid (PA) in cultured beta-cells and islets, we demonstrated that chronic exposure to lipids leads to reduced viability and inhibition of cell cycle progression concurrent with downregulation of a pro-growth/survival kinase AKT, independent of glucose. This AKT downregulation by PA treatment is correlated with a consistent induction of mTOR/S6K activity concurrent with AKT downregulation. Inhibiting mTOR activity restores AKT activity and allows beta-cells to gain proliferation capacity that are lost after high fat diet exposure. In summary, we elucidated a novel mechanism for which lipid exposure may cause the dipole effects on beta-cell growth, where mTOR acts as a lipid sensor. These mechanisms can be novel targets for future therapeutic developments.

cell biology↗

bioRxiv2020

Identification of VIMP as a gene inhibiting cytokine production in human CD4+ effector T cells

Many players regulating the CD4+ T cell-mediated inflammatory response have already been identified. However, the critical nodes that constitute the regulatory and signalling networks underlying CD4 T cell responses are still missing. Using a correlation network-guided strategy based on time-series transcriptome data of human CD4+CD25- effector T cells (Teffs), here we identified VIMP (VCP-interacting membrane protein), one of the 25 genes encoding selenocysteine in humans, as a gene regulating the effector functions of human CD4 T cells. Knocking-down VIMP in Teffs enhanced their proliferation and expression of several cytokines, including IL-2 and CSF2. We identified VIMP as an endogenous inhibitor of cytokine production in Teffs via both, the E2F5 transcription regulatory pathway and the Ca2+/NFATC2 signalling pathway. Our work not only indicates that VIMP might be a promising therapeutic target for various diseases involving CD4 T cells, but also shows that our network-guided approach might be generally applicable to different types of cells and can significantly aid in predicting new functions of the genes of interest.One-sentence summary Using a network-guided approach, we identified that Selenoprotein S (SELS or VIMP) negatively regulates cytokine expression of human CD4+ effector T cells via the E2F5 and calcium Ca2+/NFATC2 pathways.Competing Interest StatementThe authors have declared no competing interest.View Full Text

immunology↗

bioRxiv2020

Causal dynamical modelling predicts novel regulatory genes of FOXP3 in human regulatory T cells

Regulatory T cells (Tregs), characterized as a CD4+CD25+FOXP3+ subset of T cells, are vital to the induction of immune tolerance and the maintenance of immune homeostasis. While target genes of Treg master regulator FOXP3 have been identified, the upstream regulatory machinery of FOXP3 still remains largely unknown. Here we dynamically model causal relationships among genes from available time-series genome-scale datasets, to predict direct or indirect regulatory genes of FOXP3 in human primary Tregs. From the whole genome, we selected five top ranked candidates for further experimental validation. Following knockdown, three out of the five candidates indeed showed significant effects on the mRNA expression of FOXP3. Further experiments showed that one out of these three predicted candidates, namely nuclear receptor binding factor 2 (NRBF2), also affected FOXP3 protein expression. These results open new doors to identify potential new mechanisms of immune related diseases.

systems biology↗

bioRxiv2019

PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis

Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme into the tricarboxylic acid (TCA) cycle. Here we show that PARK7/DJ-1, a key familial Parkinsons disease (PD) gene, is a pacemaker controlling PDH activity in CD4 regulatory T cells (Tregs). DJ-1 bound to PDH-E1 beta (PDHB), inhibiting the phosphorylation of PDH-E1 alpha (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS). Dj-1 depletion impaired Treg proliferation and cellularity maintenance in older mice, increasing the severity during the remission phase of experimental autoimmune encephalomyelitis (EAE). The compromised proliferation and differentiation of Tregs in Dj-1 knockout mice were caused via regulating PDH activity. These findings provide novel insight into the already complicated regulatory machinery of the PDH complex and demonstrate that the DJ-1-PDHB axis represents a potent target to maintain Treg homeostasis, which is dysregulated in many complex diseases.

biochemistry↗

bioRxiv2019

EVALUATION OF OSTEOINDUCTIVITY OF DIFFERENT CALCIUM PHOSPHATE AND PTMC-CALCIUM PHOSPHATE COMPOSITE BIOMATERIALS IN A SHEEP MODEL

Osteoinduction refers to de novo bone formation induced by biomaterials in places where physiologically no bone tissue is formed. Biomaterials with osteoinductive capacities have been shown to fill bone defects of critical sizes with ubiquitous new bone formation. Therefore, osteoinduction has been regarded as an important characteristic for biomaterials aiming at bone regeneration. In our study, we tested osteoinductive capacities of different calcium phosphate bioceramic particles, calcium phosphate scaffolds, and porous poly(trimethylene carbonate)(PTMC)-calcium phosphate composite scaffolds in a sheep model. Biphasic calcium phosphate (BCP) particles of 45-150 m and 150-500 m, microporous {beta}-tricalcium phosphate ({beta}-TCP) particles of 45-150 m, non-microporous {beta}-TCP particles of 45-150 m and 150-500 m, and porous {beta}-TCP scaffolds were implanted in sheep long dorsal muscle for three and nine months. Likewise, porous composite scaffolds, in which BCP particles, microporous {beta}-TCP particles and {beta}-TCP particles, all of 45-150 m, had been incorporated into PTMC matrices, were implanted in sheep long dorsal muscle for three and nine months. Porous PTMC scaffolds were implanted as controls. Abundant new bone formation was induced by BCP particles of both size ranges, the {beta}-TCP scaffold was also able to induce new bone formation at both three and nine months follow up, while no new bone formation was induced by the other biomaterials. Implantation of the abovementioned biomaterials led to uneventful degradation of the PTMC matrices and the incorporated calcium phosphate particles, and provoked no obvious tissue reaction. Future studies are needed to determine the optimal composition of composite biomaterials based on PTMC and calcium phosphate to produce osteoinductive composites.

bioengineering↗