Biology subjects

Pang, D.

Publications and source records attributed to Pang, D..

10 recordsLinked to original sources

bioRxiv2025

Two-Phase Coding Strategy by CA1 Pyramidal Neurons: Linking Spatiotemporal Integration to Predictive Behavior

Space and time are fundamental components of memory, yet how the brain encodes these dimensions to guide behavior remains unclear. Using virtual-reality environments, we uncovered a two-phase neural code in hippocampus CA1 that represents time or distance through two functional pyramidal subpopulations, PyrUp and PyrDown. In Phase I, PyrUp activity synchronously increases to mark the initiation of encoding; In Phase II, their activity decays at heterogeneous, neuron-specific rates, creating a gradual divergence in across-population firing rates that scales with elapsed time. Conversely, PyrDown activity initially decreases before gradually rising. The crossover point, where rising PyrDown activity surpasses declining PyrUp activity, precedes predictive licking behavior. Combining optogenetics and computational modeling, we provided circuit-level evidence that PyrUp neurons primarily process locomotion-related inputs regulated by somatostatin-positive interneurons, whereas PyrDown neurons mainly receive reward-related inputs gated by parvalbumin-positive interneurons. These findings advance our understanding of how hippocampal circuits compute spatiotemporal information to inform behavior.

neuroscience↗

bioRxiv2025

Exploring Erdr1-Mid1 Axis: Shared Risk Factors and Molecular Mechanisms in Aging and Degenerative Diseases

Aging and degenerative diseases are characterized by the progressive decline in cellular, tissue, and organ function, resulting in a significant reduction in quality of life and posing major medical challenges. This highlights the urgent need to elucidate the underlying mechanisms and to develop innovative therapeutic approaches. In this study, we identify Erdr1 and Mid1 as shared risk factors for aging and multiple degenerative diseases. We propose that they contribute to disease progression by modulating oxidative stress, a well-established driver of aging and degenerative processes. We demonstrate that Erdr1 and Mid1 are both involved in oxidative stress regulation. Notably, Erdr1 undergoes alternative splicing in response to oxidative stress, resulting in reduced production of its antioxidant isoforms (Erdr1-177 and Erdr1-209), while promoting the secretion of its pro-oxidant isoform (Erdr1-145). Moreover, Erdr1-145 exacerbates oxidative damage by activating Mid1, a key inducer of oxidative stress. The Erdr1-Mid1-oxidative stress axis provides a molecular mechanistic basis for their shared role as risk factors for aging and degenerative diseases. Furthermore, we propose therapeutic strategies to mitigate cellular damage by regulating Erdr1 levels, implying a straightforward and effective approach for in situ repair of damage associated with aging and degenerative diseases. HighlightsO_LIErdr1 and Mid1 are shared risk factors in aging and multiple degenerative diseases. C_LIO_LIErdr1 and Mid1 contribute to cellular damage and degeneration by modulating oxidative stress. C_LIO_LIErdr1 undergoes alternative splicing in response to oxidative stress, downregulating antioxidant isoforms (Erdr1-177 and 209) while promoting the secretion of prooxidant isoform (Erdr1-145). C_LIO_LIErdr1-145 robustly primes oxidative stress by promoting Mid1 activation, thereby highlighting the role of the Erdr1-Mid1-oxidative stress axis in cellular damage. C_LIO_LIModulating Erdr1 indicates promising strategies for in situ repair of damage associated with aging and degenerative diseases. C_LI

immunology↗

bioRxiv2023

A CA1 circuit motif that signals the start of information integration

To navigate their environments effectively, animals frequently integrate distance or time information to seek food and avoid threats. This integration process is thought to engage hippocampal neurons that fire at specific distances or times. Using virtual-reality environments, we uncovered two previously unknown functional subpopulations of CA1 pyramidal neurons that encode distance or time through a novel two-phase coding mechanism. The first subpopulation exhibits a collective increase in activity that peaks at similar times, marking the onset of integration; subsequently, individual neurons gradually diverge in their firing rates due to heterogeneous decay rates, enabling time encoding. In contrast, the second subpopulation initially decreases its activity before gradually ramping up. Closed-loop optogenetic experiments revealed that inactivating somatostatin-positive (SST) interneurons disrupts the first subpopulation, behaviorally impairing integration accuracy, while inactivating parvalbumin-positive (PV) interneurons disrupts the second subpopulation, impairing behavior during integration initiation. These findings support the conclusion that SST interneurons establish an integration window, while PV interneurons generate a reset to reinitiate integration. This study elucidates parallel neural circuits that facilitate distinct aspects of distance or time integration, offering new insights into the computations underlying navigation and memory encoding.

neuroscience↗

bioRxiv2021

PCBP1 Deficient Pigs Hold the Potential to Inhibit CSFV Infection

Classical swine fever virus (CSFV), pathogen of classic swine fever, has caused severe economic losses worldwide. Poly (rC)-binding protein 1 (PCBP1), interacting with Npro of CSFV, plays a vital role in CSFV growth. Here, our research is the first report to generate PCBP1 knockout pigs via gene editing technology. The PCBP1 knockout pigs exhibited normal birth weight, reproductive-performance traits, and developed normally. Viral challenge results indicated that primary cells isolated from F0 and F1 generation pigs could significantly reduce CSFV infection. Additional mechanism exploration further confirmed that PCBP1 KO mediated antiviral effect is related with the activation of type I interferon. Beyond showing that gene editing strategy can be used to generate PCBP1 KO pigs, our study introduces a valuable animal model for further investigating infection mechanisms of CSFV that help to develop better antiviral solution. ImportanceAs a negative regulator in immune modulation, the effects of PCBP1 on viral replication have been found to be valuable. Here, this study was the first report to generate PCBP1 knockout pigs with normal pregnancy rate and viability. Primary cells isolated from F0 and F1 generation PCBP1 knockout pigs could significantly reduce CSFV infection. The PCBP1 knockout pigs could be used as a natural host models for investigating the effects of PCBP1-mediating critical interactions on viral replication and helping to develop better antiviral solution.

molecular biology↗

bioRxiv2020

Identification of Cross-Reactive CD8+ T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants

Despite the growing knowledge of T cell responses and their epitopes in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins, N361-369 (KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369 mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369 epitope could be processed and endogenously presented to elicit the activation and cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.

immunology↗

bioRxiv2019

Pre-warming before general anesthesia with isoflurane delays the onset of hypothermia in rats

General anesthesia causes hypothermia by impairing normal thermoregulatory mechanisms. Redistribution of warm blood from the core to the periphery is the primary mechanism in the development of hypothermia and begins following induction of anesthesia. Raising skin temperature before anesthesia reduces the temperature gradient between core and periphery, decreasing the transfer of heat. This prospective, crossover study (n = 17 adult male and female SD rats) compared three treatment groups: PW1% (pre-warming to increase core temperature 1% over baseline), PW40 (pre-warming to increase core temperature to 40{degrees}C) and NW (no warming). The PW1% group was completed first to ensure tolerance of pre-warming. Treatment order was then randomized and alternated after a washout period. Once target temperature was achieved, anesthesia was induced and maintained with isoflurane in oxygen without further external temperature support. Pre-warming was effective at delaying the onset of hypothermia, with a significant difference between PW1% (11.2 minutes) and PW40 (14.7 minutes, p = 0.0044 (95%CI -12 to -2.2), PW40 and NW (6.0 minutes, p = 0.003 (95%CI 1.8 to 8.7) and PW1% and PW40 (p = 0.004, 95%CI -12 to -2.2). The rate of heat loss in the pre-warmed groups exceed that of the NW group: PW1% versus NW (p = 0.005, 95%CI 0.004 to 0.027), PW40 versus NW (p < 0.0001, 95%CI 0.014 to 0.036) and PW1% versus PW40 (p = 0.07, 95%CI -0.021 to 0.00066). Pre-warming alone confers a protective effect against hypothermia during volatile anesthesia; however, longer duration procedures would require additional heating support.

pharmacology and toxicology↗

bioRxiv2019

Intraperitoneal injection of sodium pentobarbital is associated with pain in rats.

An effective and pain-free killing method is required to achieve the goal of euthanasia, a \"good death\". Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control.\n\nAdult male and female Sprague Dawley (SD) and female Wistar rats (N = 112) were block randomised by sex and strain to receive one of four treatments: 1) 800 mg/kg PB (pH 11); 2) 800 mg/kg PB with 4 mg/kg lidocaine (PB+lido); 3) saline or 4) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale [RGS], writhing, back arching) was evaluated at baseline, before loss of righting reflex (PB and PB+lido groups), 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups).\n\nIn the vehicle control groups, the RGS scores were increased at 151s PI (SD: p = 0.0008, 95%CI -0.731 to -0.202) from baseline, as was relative frequency of writhing (SD: p < 0.00001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0070, 95%CI -0.768 to -0.118; Wistar: p = 0.0236, 95%CI -0.907 to -0.0742) but the relative frequency of writhing did not (p > 0.05). The RGS scores and the relative frequency of writhing remained low in the PB, PB+lido and saline groups (p > 0.05). Back arching increased from baseline in the PB+lido group before loss of righting reflex and in the vehicle control group (SD rats) at 151s PI (p < 0.05).\n\nThese results show that IP PB results in signs associated with pain. The sedative effects of PB limit behavioral assessment.

physiology↗

bioRxiv2019

Gene Panel Sequencing in a Chinese High-risk Breast Cancer Cohort

Currently, over 20 genes have been defined that can confer susceptibility for high-risk breast cancer. Although research has proved the utility of multiple-gene sequencing in the assessment of breast cancer risk, there is little data from China patients. Here, we use a multiple-gene sequencing panel to identify the variant spectrum in Chinese high-risk breast cancer subjects.\n\nA total of 829 Chinese high-risk breast cancer patients participated in the research. The coding regions of 115 hereditary cancer susceptibility genes were sequenced using a next generation sequencing platform. In total, 193 pathogenic variants were identified in 45 genes from 177 patients. The pathogenic variant carrier rate is 21.4%: with 10.5% patients carrying a BRCA1 or BRCA2 mutation only, 10.0% of patients carried non-BRCA gene mutations only, while 1.0% of patients carried both a BRCA1/2 and a non-BRCA gene mutation. Variants of uncertain significance (VUS) totaling 2632 were identified in 115 genes from 787 of 829 patients: 82.5% patients carried more than one VUS, and only 5.1% patients did not carry any VUS. Families carrying pathogenic variants were tracked and adenoma was founded in three of them. Our data provide a comprehensive analysis of potential susceptibility variations of high-risk for breast cancer in a Chinese population. This data will be useful for the comparison of the susceptibility variation spectrum between different populations and to discover potential pathogenic variants to improve the prevention and treatment of high-risk breast cancer.

cancer biology↗

bioRxiv2018

Development of whole-porcine monoclonal antibodies with potent neutralization activity against classical swine fever virus (CSFV) from single B cells

Classical swine fever (CSF) is a highly contagious swine disease found worldwide that has caused devastating economic losses. However, there are few efficacious mAbs against the CSF virus (CSFV) that can be used for treatment because most mAbs against CSFV are derived from mouse hybridoma cells and these murine mAbs have disadvantages of inefficient effector functions elicitations and high immunogenicity in vivo. Accordingly, we characterized whole-porcine anti-CSFV neutralizing mAbs (NAbs) isolated directly from single B cells sorted from a CSFV-vaccinated pig using the fluoresceinated conserved linear neutralizing epitope of the CSFV E2 protein and fluorophore conjugated goat anti-pig IgG. Immunoglobulin (Ig) genes were isolated via nested PCR, and two porcine mAbs termed HK24 and HK44 were produced. We determined that these mAbs can bind to E2 protein and recognize sites within this major antigenic epitope. In addition, we found that mAbs HK24 and HK44 exhibit potent neutralizing activity against CSFV, and they can protect PK-15 cells from infections in vitro with potent IC50 values of 9.3 g/ml and 0.62 g/ml, respectively. Notably, we demonstrated that these two mAbs can be used as novel reagents for detecting virus infection. These data suggest that our results not only provide a method for efficiently obtaining mAbs against CSFV but also offer promising mAb candidates for development of antibody-based diagnostic and antiviral agents.\n\nImportanceNeutralizing monoclonal antibodies (NAbs) can prevent and may slow the spread of virus infection. The discovery of NAbs that recognize classical swine fever virus (CSFV) necessitates new technologies because the NAbs produced by immunization and hybridoma technology could not be transferred to in vivo research. Multiple full-length human therapeutic antibodies have been produced via single-cell polymerase chain reactions but whole-porcine NAbs for CSFV have not been generated. In this study, two whole-porcine mAbs, named HK24 and HK44, were isolated from epitope-specific single B cells. We demonstrate that these two mAbs have potent neutralizing activity against CSFV and can protect cells against viral infection. Therefore, they may facilitate the development of vaccines or antiviral drugs that offer the advantages of stability and low immunogenicity.

molecular biology↗

bioRxiv2018

Genetically modified pigs are protected from classical swine fever virus

Classical swine fever (CSF) caused by classical swine fever virus (CSFV) is among the most detrimental diseases, and leads to significant economic losses in the swine industry. Despite efforts by many government authorities try to stamp out the disease from national pig populations, the disease remains widespread. Here, antiviral small hairpin RNAs (shRNAs) were selected and then inserted at the porcine ROSA26 (pROSA26) locus via a CRISPR/Cas9-mediated knock-in strategy. Finally, anti-CSFV transgenic (TG) pigs were produced by somatic nuclear transfer (SCNT). Importantly, in vitro and in vivo viral challenge assays demonstrated that these TG pigs could effectively limit the growth of CSFV and reduced CSFV-associated clinical signs and mortality, and the disease resistance was stably transmitted to F1-generation. The use of these TG pigs can improve the well-being of livestock and substantially reduce virus-related economic losses. Additionally, this antiviral approach may provide a reference for future antiviral research.\n\nAuthor summaryClassical swine fever (CSF), caused by classical swine fever virus (CSFV), and is a highly contagious, often fatal porcine disease with significant economic losses. Due to its economic importance to the pig industry, the biology and pathogenesis of CSFV have been investigated extensively. Despite efforts by many government authorities to stamp out the disease from national pig populations, the disease remains widespread in some regions and seems to be waiting for the reintroduction and the next round of disease outbreaks. These highlight the necessity and urgency of developing more effective approaches to eradicate the challenging CSFV. In this study, we successfully produced anti-CSFV transgenic pigs and confirmed that these transgenic pigs could effectively limit the growth of CSFV in vivo and in vitro and that the disease resistance traits in the TG founders can be stably transmitted to their F1-generation offspring. This study suggests that these TG pigs can improve the well-being of livestock and contribute to offer potential benefits over commercial vaccination. The use of these TG pigs can improve the well-being of livestock and substantially reduce CSFV-related economic losses.

genomics↗