2023 Vol. 44, No. 5

The common marmoset (Callithrix jacchus) has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies. Epileptic marmosets have been independently reported in two Asian primate research centers. Nevertheless, the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated. Here, we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing. We identified 14 558 184 single nucleotide polymorphisms (SNPs) from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples. Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers. In addition, SNP and copy number variation (CNV) analyses suggested that the WW domain-containing oxidoreductase (WWOX) and Tyrosine-protein phosphatase nonreceptor type 21 (PTPN21) genes may be associated with epilepsy in marmosets. Notably, KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets. This study provides valuable population genomic resources for marmosets in two Asian primate centers. Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers, while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.
Activating transcription factor 6 (ATF6), one of the three sensor proteins in the endoplasmic reticulum (ER), is an important regulator of ER stress-induced apoptosis. ATF6 resides in the ER and, upon activation, is translocated to the Golgi apparatus, where it is cleaved by site-1 protease (S1P) to generate an amino-terminal cytoplasmic fragment. Although recent studies have made progress in elucidating the regulatory mechanisms of ATF6, its function during early porcine embryonic development under high-temperature (HT) stress remains unclear. In this study, zygotes were divided into four groups: control, HT, HT+ATF6 knockdown, and HT+PF (S1P inhibitor). Results showed that HT exposure induced ER stress, which increased ATF6 protein expression and led to a decrease in the blastocyst rate. Next, ATF6 expression was knocked down in HT embryos under microinjection of ATF6 double-stranded RNA (dsRNA). Results revealed that ATF6 knockdown (ATF6-KD) attenuated the increased expression of CHOP, an ER stress marker, and Ca2+ release induced by HT. In addition, ATF6-KD alleviated homeostasis dysregulation among organelles caused by HT-induced ER stress, and further reduced Golgi apparatus and mitochondrial dysfunction in HT embryos. AIFM2 is an important downstream effector of ATF6. Results showed that ATF6-KD reduced the occurrence of AIFM2-mediated embryonic apoptosis at HT. Taken together, our findings suggest that ATF6 is a crucial mediator of apoptosis during early porcine embryonic development, resulting from HT-induced ER stress and disruption of organelle homeostasis.
Animals that live in seasonal environments adjust their reproduction cycle to optimize seasonal forage quality. Giant pandas (Ailuropoda melanoleuca) are seasonal altitudinal migrants that feed on bamboo shoots and leaves with different nutritional quality. However, the importance of bamboo shoots to giant pandas, especially small and isolated populations, is not fully appreciated. Here, we explored whether mating time of giant pandas is shaped by bamboo shoot phenology. We also assessed the intensity of ongoing bamboo shoot harvesting by local communities in 42 giant panda reserves based on questionnaire surveys. Varying intensity and protection levels of bamboo shoot harvesting were found. From these data, we developed a priority ranking scheme of protection areas for this key food resource. Our study showed that pandas time their mating behavior to coincide with bamboo shoot phenology due to the high nutritional demands associated with mating and pregnancy. We also found that bamboo shoots were not well protected in many places. Liangshan, Daxiangling, and Xiaoxiangling, containing the most isolated panda populations, were identified as the areas with the most urgent need of protection. Furthermore, equal attention should be paid to the QiongL-B population, as this region holds considerable potential to serve as a corridor between the Minshan and Qionglai populations. To address the challenges posed by bamboo shoot harvesting, we recommend establishing more practical bamboo shoot management policies, increasing public awareness of bamboo shoot protection, and providing alternative sources of income for local communities.
Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer’s disease (AD). High-frequency stimulation (HFS)-induced long-term potentiation (LTP) has been widely used to study synaptic plasticity, with impaired LTP found to be associated with AD. However, the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated. Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear. Herein, we induced LTP in the hippocampal CA1 region of wild-type (WT) and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region. We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes (DEGs) in mice with normal LTP, and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP. We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction. Among them, we found that the expression of Pygm, which catabolizes glycogen, was also decreased in AD patients. We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice, while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice. Moreover, we showed that PYGM directly regulated energy generation in neurons. Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function, but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.
Accurately recognizing facial expressions is essential for effective social interactions. Non-human primates (NHPs) are widely used in the study of the neural mechanisms underpinning facial expression processing, yet it remains unclear how well monkeys can recognize the facial expressions of other species such as humans. In this study, we systematically investigated how monkeys process the facial expressions of conspecifics and humans using eye-tracking technology and sophisticated behavioral tasks, namely the temporal discrimination task (TDT) and face scan task (FST). We found that monkeys showed prolonged subjective time perception in response to Negative facial expressions in monkeys while showing longer reaction time to Negative facial expressions in humans. Monkey faces also reliably induced divergent pupil contraction in response to different expressions, while human faces and scrambled monkey faces did not. Furthermore, viewing patterns in the FST indicated that monkeys only showed bias toward emotional expressions upon observing monkey faces. Finally, masking the eye region marginally decreased the viewing duration for monkey faces but not for human faces. By probing facial expression processing in monkeys, our study demonstrates that monkeys are more sensitive to the facial expressions of conspecifics than those of humans, thus shedding new light on inter-species communication through facial expressions between NHPs and humans.
Conjugative transfer of antibiotic resistance genes (ARGs) by plasmids is an important route for ARG dissemination. An increasing number of antibiotic and nonantibiotic compounds have been reported to aid the spread of ARGs, highlighting potential challenges for controlling this type of horizontal transfer. Development of conjugation inhibitors that block or delay the transfer of ARG-bearing plasmids is a promising strategy to control the propagation of antibiotic resistance. Although such inhibitors are rare, they typically exhibit relatively high toxicity and low efficacy in vivo and their mechanisms of action are inadequately understood. Here, we studied the effects of dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, on conjugation. DHA inhibited the conjugation of the IncI2 and IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 160-fold in vitro in Escherichia coli, and more than two-fold (IncI2 plasmid) in vivo in a mouse model. It also suppressed the transfer of the IncX3 plasmid carrying the carbapenem resistance gene blaNDM-5 by more than two-fold in vitro. Detection of intracellular adenosine triphosphate (ATP) and proton motive force (PMF), in combination with transcriptomic and metabolomic analyses, revealed that DHA impaired the function of the electron transport chain (ETC) by inhibiting the tricarboxylic acid (TCA) cycle pathway, thereby disrupting PMF and limiting the availability of intracellular ATP for plasmid conjugative transfer. Furthermore, expression levels of genes related to conjugation and pilus generation were significantly down-regulated during DHA exposure, indicating that the transfer apparatus for conjugation may be inhibited. Our findings provide new insights into the control of antibiotic resistance and the potential use of DHA.
Previous studies have shown that Vibrio splendidus infection causes mitochondrial damage in Apostichopus japonicus coelomocytes, leading to the production of excessive reactive oxygen species (ROS) and irreversible apoptotic cell death. Emerging evidence suggests that mitochondrial autophagy (mitophagy) is the most effective method for eliminating damaged mitochondria and ROS, with choline dehydrogenase (CHDH) identified as a novel mitophagy receptor that can recognize non-ubiquitin damage signals and microtubule-associated protein 1 light chain 3 (LC3) in vertebrates. However, the functional role of CHDH in invertebrates is largely unknown. In this study, we observed a significant increase in the mRNA and protein expression levels of A. japonicus CHDH (AjCHDH) in response to V. splendidus infection and lipopolysaccharide (LPS) challenge, consistent with changes in mitophagy under the same conditions. Notably, AjCHDH was localized to the mitochondria rather than the cytosol following V. splendidus infection. Moreover, AjCHDH knockdown using siRNA transfection significantly reduced mitophagy levels, as observed through transmission electron microscopy and confocal microscopy. Further investigation into the molecular mechanisms underlying CHDH-regulated mitophagy showed that AjCHDH lacked an LC3-interacting region (LIR) for direct binding to LC3 but possessed a FB1 structural domain that binds to SQSTM1. The interaction between AjCHDH and SQSTM1 was further confirmed by immunoprecipitation analysis. Furthermore, laser confocal microscopy indicated that SQSTM1 and LC3 were recruited by AjCHDH in coelomocytes and HEK293T cells. In contrast, AjCHDH interference hindered SQSTM1 and LC3 recruitment to the mitochondria, a critical step in damaged mitochondrial degradation. Thus, AjCHDH interference led to a significant increase in both mitochondrial and intracellular ROS, followed by increased apoptosis and decreased coelomocyte survival. Collectively, these findings indicate that AjCHDH-mediated mitophagy plays a crucial role in coelomocyte survival in A. japonicus following V. splendidus infection.
Under increasing anthropogenic pressure, species with a previously contiguous distribution across their ranges have been reduced to small fragmented populations. The critically endangered Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis), once commonly observed in the Yangtze River-Poyang Lake junction, is now rarely seen in the river-lake corridor. In this study, static passive acoustic monitoring techniques were used to detect the biosonar activities of the Yangtze finless porpoise in this unique corridor. Generalized linear models were used to examine the correlation between these activities and anthropogenic impacts from the COVID-19 pandemic lockdown and boat navigation, as well as environmental variables, including hydrological conditions and light levels. Over approximately three consecutive years of monitoring (2020–2022), porpoise biosonar was detected during 93% of logged days, indicating the key role of the corridor for finless porpoise conservation. In addition, porpoise clicks were recorded in 3.80% of minutes, while feeding correlated buzzes were detected in 1.23% of minutes, suggesting the potential existence of localized, small-scale migration. Furthermore, both anthropogenic and environmental variables were significantly correlated with the diel, lunar, monthly, seasonal, and annual variations in porpoise biosonar activities. During the pandemic lockdown period, porpoise sonar detection showed a significant increase. Furthermore, a significant negative correlation was identified between the detection of porpoise click trains and buzzes and boat traffic intensity. In addition to water level and flux, daylight and moonlight exhibited significant correlations with porpoise biosonar activities, with markedly higher detections at night and quarter moon periods. Ensuring the spatiotemporal reduction of anthropogenic activities, implementing vessel speed restrictions (e.g., during porpoise migration and feeding), and maintaining local natural hydrological regimes are critical factors for sustaining porpoise population viability.
Letter to the editor
Hypoxia is a common environmental stress factor in aquatic organisms, which varies among fish species. However, the mechanisms underlying the ability of fish species to tolerate hypoxia are not well known. Here, we showed that hypoxia response in different fish species was affected by lipid catabolism and preference for lipid or carbohydrate energy sources. Activation of biochemical lipid catabolism through peroxisome proliferator-activated receptor alpha (Pparα) or increasing mitochondrial fat oxidation in tilapia decreased tolerance to acute hypoxia by increasing oxygen consumption and oxidative damage and reducing carbohydrate catabolism as an energy source. Conversely, lipid catabolism inhibition by suppressing entry of lipids into mitochondria in tilapia or individually knocking out three key genes of lipid catabolism in zebrafish increased tolerance to acute hypoxia by decreasing oxygen consumption and oxidative damage and promoting carbohydrate catabolism. However, anaerobic glycolysis suppression eliminated lipid catabolism inhibition-promoted hypoxia tolerance in adipose triglyceride lipase (atgl) mutant zebrafish. Using 14 fish species with different trophic levels and taxonomic status, the fish preferentially using lipids for energy were more intolerant to acute hypoxia than those preferentially using carbohydrates. Our study shows that hypoxia tolerance in fish depends on catabolic preference for lipids or carbohydrates, which can be modified by regulating lipid catabolism.
Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction. However, action recognition currently used in non-human primate (NHP) research relies heavily on intense manual labor and lacks standardized assessment. In this work, we established two standard benchmark datasets of NHPs in the laboratory: MonkeyinLab (MiL), which includes 13 categories of actions and postures, and MiL2D, which includes sequences of two-dimensional (2D) skeleton features. Furthermore, based on recent methodological advances in deep learning and skeleton visualization, we introduced the MonkeyMonitorKit (MonKit) toolbox for automatic action recognition, posture estimation, and identification of fine motor activity in monkeys. Using the datasets and MonKit, we evaluated the daily behaviors of wild-type cynomolgus monkeys within their home cages and experimental environments and compared these observations with the behaviors exhibited by cynomolgus monkeys possessing mutations in the MECP2 gene as a disease model of Rett syndrome (RTT). MonKit was used to assess motor function, stereotyped behaviors, and depressive phenotypes, with the outcomes compared with human manual detection. MonKit established consistent criteria for identifying behavior in NHPs with high accuracy and efficiency, thus providing a novel and comprehensive tool for assessing phenotypic behavior in monkeys.
Planarians represent the most primitive bilateral triploblastic animals. Most planarian species exhibit mechanisms for whole-body regeneration, exemplified by the regeneration of their cephalic ganglion after complete excision. Given their robust whole-body regeneration capacity, planarians have been model organisms in regenerative research for more than 240 years. Advancements in research tools and techniques have progressively elucidated the mechanisms underlying planarian regeneration. Accurate cell-cell communication is recognized as a fundamental requirement for regeneration. In recent decades, mechanisms associated with such communication have been revealed at the cellular level. Notably, stem cells (neoblasts) have been identified as the source of all new cells during planarian homeostasis and regeneration. The interplay between neoblasts and somatic cells affects the identities and proportions of various tissues during homeostasis and regeneration. Here, this review outlines key discoveries regarding communication between stem cell compartments and other cell types in planarians, as well as the impact of communication on planarian regeneration. Additionally, this review discusses the challenges and potential directions of future planarian research, emphasizing the sustained impact of this field on our understanding of animal regeneration.
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