Synapse location during growth depends on glia location.

Synaptic contacts are largely established during embryogenesis and are then maintained during growth. To identify molecules involved in this process, we conducted a forward genetic screen in C. elegans and identified cima-1. In cima-1 mutants, synaptic contacts are correctly established during embryogenesis, but ectopic synapses emerge during postdevelopmental growth. cima-1 encodes a solute carrier in the SLC17 family of transporters that includes sialin, a protein that when mutated in humans results in neurological disorders. cima-1 does not function in neurons but rather functions in the nearby epidermal cells to correctly position glia during postlarval growth. Our findings indicate that CIMA-1 antagonizes the FGF receptor (FGFR), and does so most likely by inhibiting FGFR's role in epidermal-glia adhesion rather than signaling. Our data suggest that epidermal-glia crosstalk, in this case mediated by a transporter and the FGF receptor, is vital to preserve embryonically derived circuit architecture during postdevelopmental growth.

Gut neuroendocrine signaling regulates synaptic assembly in C. elegans.

Synaptic connections are essential to build a functional brain. How synapses are formed during development is a fundamental question in neuroscience. Recent studies provided evidence that the gut plays an important role in neuronal development through processing signals derived from gut microbes or nutrients. Defects in gut-brain communication can lead to various neurological disorders. Although the roles of the gut in communicating signals from its internal environment to the brain are well known, it remains unclear whether the gut plays a genetically encoded role in neuronal development. Using C. elegans as a model, we uncover that a Wnt-endocrine signaling pathway in the gut regulates synaptic development in the brain. A canonical Wnt signaling pathway promotes synapse formation through regulating the expression of the neuropeptides encoding gene nlp-40 in the gut, which functions through the neuronally expressed GPCR/AEX-2 receptor during development. Wnt-NLP-40-AEX-2 signaling likely acts to modulate neuronal activity. Our study reveals a genetic role of the gut in synaptic development and identifies a novel contribution of the gut-brain axis.

Temperature regulates synaptic subcellular specificity mediated by inhibitory glutamate signaling.

Environmental factors such as temperature affect neuronal activity and development. However, it remains unknown whether and how they affect synaptic subcellular specificity. Here, using the nematode Caenorhabditis elegans AIY interneurons as a model, we found that high cultivation temperature robustly induces defects in synaptic subcellular specificity through glutamatergic neurotransmission. Furthermore, we determined that the functional glutamate is mainly released by the ASH sensory neurons and sensed by two conserved inhibitory glutamate-gated chloride channels GLC-3 and GLC-4 in AIY. Our work not only presents a novel neurotransmission-dependent mechanism underlying the synaptic subcellular specificity, but also provides a potential mechanistic insight into high-temperature-induced neurological defects.

OGT-1 regulates synaptic assembly through the insulin signaling pathway.

The formation and maintenance of synapses are precisely regulated, and the misregulation often leads to neurodevelopmental or neurodegenerative disorders. Besides intrinsic genetically encoded signaling pathways, synaptic structure and function are also regulated by extrinsic factors, such as nutrients. O-GlcNAc transferase (OGT), a nutrient sensor, is abundant in the nervous system and required for synaptic plasticity, learning, and memory. However, whether OGT is involved in synaptic development and the mechanism underlying the process are largely unknown. In this study, we found that OGT-1, the OGT homolog in C. elegans, regulates the presynaptic assembly in AIY interneurons. The insulin receptor DAF-2 acts upstream of OGT-1 to promote the presynaptic assembly by positively regulating the expression of ogt-1. This insulin-OGT-1 axis functions most likely by regulating neuronal activity. In this study, we elucidated a novel mechanism for synaptic development, and provided a potential link between synaptic development and insulin-related neurological disorders.

O-GlcNAc transferase Ogt regulates embryonic neuronal development through modulating Wnt/ß-catenin signaling.

Ogt-mediated O-GlcNAcylation is enriched in the nervous system and involves in neuronal development, brain function and neurological diseases. However, the roles of Ogt and O-GlcNAcylation in embryonic neurogenesis have remained largely unknown. Here, we show that Ogt is highly expressed in embryonic brain, and Ogt depletion reduces the proliferation of embryonic neural stem cells and migration of new born neurons. Ogt depletion in cultured hippocampal neurons impairs neuronal maturation, including reduced dendritic numbers and length, and immature development of spines. Mechanistically, Ogt depletion decreases the activity of Wnt/ß-catenin signaling. Ectopic ß-catenin rescues neuronal developmental deficits caused by Ogt depletion. Ogt also regulates human cortical neurogenesis in forebrain organoids derived from induced pluripotent stem cells. Our findings reveal the essential roles and mechanisms of Ogt-mediated O-GlcNAc modification in regulating mammalian neuronal development.

Coupling Bifunctional Nanozyme-Mediated Catalytic Signal Amplification and Label-Free SERS with Immunoassays for Ultrasensitive Detection of Pathogens in Milk Samples.

Rapid and sensitive detection of foodborne bacteria is of great significance in guaranteeing food safety and preventing foodborne diseases. A bifunctional Au@Pt core-shell nanozyme with excellent catalytic properties and high surface-enhanced Raman scattering (SERS) activity was developed for the highly sensitive detection of Salmonella typhimurium based on a label-free SERS strategy. The ultrathin Pt shell (about 1 nm) can catalyze Raman-inactive molecules into Raman-active reporters, greatly amplifying the amount of signal molecules. Moreover, the Au core serves as an active SERS substrate to enhance the signal of reporter molecules, further significantly improving the detection sensitivity. Benefiting from the excellent properties, such a bifunctional Au@Pt nanozyme was integrated with a magnetic immunoassay to construct a label-free SERS platform for the highly sensitive detection of S. typhi with a low detection limit of 10 CFU mL-1. Also, the Au@Pt-based SERS platform exhibited excellent selectivity and was successfully utilized for the detection of S. typhi in milk samples by a portable Raman spectrometer. Our demonstration of the bifunctional nanozyme-based SERS strategy provides an efficient pathway to improve the sensitivity of label-free SERS detection of pathogens and holds great promise in food safety, environmental analysis, and other biosensing fields.

Root vertical spatial stress: A method for enhancing rhizosphere effect of plants in subsurface flow constructed wetland.

The depth of the substrate of subsurface flow (SSF) constructed wetlands (CWs) is closely related to their cost and operation stability. To explore the physiological regulation mechanism of wetland plants and pollutant removal potential of SSF CWs under "vertical spatial stress of roots" (by greatly reducing the depth of the substrate in SSF CWs to limit the vertical growth space of roots, VSSR), the physiological response and wetland purification effect of a 0.1 m Canna indica L. CW under VSSR were studied compared with conventional SSF CWs (0.6 m, 1.2 m). The results demonstrated that VSSR significantly enhanced the dissolved oxygen (DO) concentration (p < 0.05) within the SSF CWs, with the DO in 0.1 m CW remaining stable at over 3 mg/L. Under the same hydraulic retention time (HRT), VSSR significantly improved the removal effect of pollutants (p < 0.05). The removal rates of COD, NH4+-N, and total phosphorus (TP) remained above 87%, and the mean removal rates of total nitrogen (TN) reached 91.71%. VSSR promoted the morphological adaptation mechanisms of plants, such as significantly increased root-shoot ratio (p < 0.05), changed biomass allocation. Plants could maintain the stability of the photosynthetic mechanism by changing the distribution of light energy. The results of microbial community function prediction demonstrated that aerobic denitrification was the main mechanism of N transformation in the 0.1 m CW under VSSR. VSSR could induce the high root activity of plants, augment the concentration of root exudates, enhance the redox environment of the plant rhizosphere, further foster the enrichment of aerobic denitrifying bacteria, and strengthen the absorption efficiency of wetland plants and substrate, thus achieving an efficient pollutant removal capacity. Studies showed that VSSR was an effective means to enhance the rhizosphere effect of plants and pollutant removal in SSF CWs.

The brassinosteroid signaling component SlBZR1 promotes tomato fruit ripening and carotenoid accumulation.

The plant hormone ethylene is essential for climacteric fruit ripening, although it is unclear how other phytohormones and their interactions with ethylene might affect fruit ripening. Here, we explored how brassinosteroids (BRs) regulate fruit ripening in tomato (Solanum lycopersicum) and how they interact with ethylene. Exogenous BR treatment and increased endogenous BR contents in tomato plants overexpressing the BR biosynthetic gene SlCYP90B3 promoted ethylene production and fruit ripening. Genetic analysis indicated that the BR signaling regulators Brassinazole-resistant1 (SlBZR1) and BRI1-EMS-suppressor1 (SlBES1) act redundantly in fruit softening. Knocking out SlBZR1 inhibited ripening through transcriptome reprogramming at the onset of ripening. Combined transcriptome deep sequencing and chromatin immunoprecipitation followed by sequencing identified 73 SlBZR1-repressed targets and 203 SlBZR1-induced targets involving major ripening-related genes, suggesting that SlBZR1 positively regulates tomato fruit ripening. SlBZR1 directly targeted several ethylene and carotenoid biosynthetic genes to contribute to the ethylene burst and carotenoid accumulation to ensure normal ripening and quality formation. Furthermore, knock-out of Brassinosteroid-insensitive2 (SlBIN2), a negative regulator of BR signaling upstream of SlBZR1, promoted fruit ripening and carotenoid accumulation. Taken together, our results highlight the role of SlBZR1 as a master regulator of tomato fruit ripening with potential for tomato quality improvement and carotenoid biofortification.

Overexpression of FBR41 enhances resistance to sphinganine analog mycotoxin-induced cell death and Alternaria stem canker in tomato.

Fumonisin B1 (FB1) and Alternaria alternate f. sp. lycopersici (AAL)-toxin are classified as sphinganine analog mycotoxins (SAMTs), which induce programmed cell death (PCD) in plants and pose health threat to humans who consume the contaminated crop products. Herein, Fumonisin B1 Resistant41 (FBR41), a dominant mutant allele, was identified by map-based cloning of Arabidopsis FB1-resistant mutant fbr41, then ectopically expressed in AAL-toxin sensitive tomato (Solanum lycopersicum) cultivar. FBR41-overexpressing tomato plants exhibited less severe cell death phenotype upon AAL-toxin treatment. Analysis of free sphingoid bases showed that both fbr41 and FBR41-overexpressing tomato plants accumulated less sphinganine and phytosphingosine upon FB1 and AAL-toxin treatment, respectively. Alternaria stem canker is a disease caused by AAL and responsible for severe economic losses in tomato production, and FBR41-overexpressing tomato plants exhibited enhanced resistance to AAL with decreased fungal biomass and less cell death, which was accompanied by attenuated accumulation of free sphingoid bases and jasmonate (JA). Taken together, our results indicate that FBR41 is potential in inhibiting SAMT-induced PCD and controlling Alternaria stem canker in tomato.

Characterization of a reassortant H11N9 subtype avian influenza virus isolated from bean goose along the East Asian-Australian flyway.

During the surveillance of avian influenza viruses in the Dongxi Lake wetland of Hubei in 2015-2016, an H11N9 avian influenza virus was isolated from a bean goose (Anser fabalis). Phylogenetic analysis showed that the HA gene of this isolate belongs to the North American lineage; however, the NA and the internal genes of the isolate were generated from the Eurasian lineage. This strain had reduced pathogenicity in mice and was capable of replication in the mouse lung without prior adaptation. This is the first report detecting H11N9 subtype influenza virus from migratory birds in central China. These findings highlight the transmission of avian influenza virus along the East Asian-Australian flyway and the need for continuing surveillance in central China.

Classic myrosinase-dependent degradation of indole glucosinolate attenuates fumonisin B1-induced programmed cell death in Arabidopsis.

The mycotoxin fumonisin B1 (FB1) causes the accumulation of reactive oxygen species (ROS) which then leads to programmed cell death (PCD) in Arabidopsis. In the process of studying FB1-induced biosynthesis of glucosinolates, we found that indole glucosinolate (IGS) is involved in attenuating FB1-induced PCD. Treatment with FB1 elevates the expression of genes related to the biosynthesis of camalexin and IGS. Mutants deficient in aliphatic glucosinolate (AGS) or camalexin biosynthesis display similar lesions to Col-0 upon FB1 infiltration; however, the cyp79B2 cyp79B3 double mutant, which lacks induction of both IGS and camalexin, displays more severe lesions. Based on the fact that the classic myrosinase ß-thioglucoside glucohydrolase (TGG)-deficient double mutant tgg1 tgg2, rather than atypical myrosinase-deficient mutant pen2-2, is more sensitive to FB1 than Col-0, and the elevated expression of TGG1, but not of PEN2, correlates with the decrease in IGS, we conclude that TGG-dependent IGS hydrolysis is involved in FB1-induced PCD. Indole-3-acetonitrile (IAN) and indole-3-carbinol (I3C), the common derivatives of IGS, were used in feeding experiments, and this rescued the severe cell death phenotype, which is associated with reduced accumulation of ROS as well as increased activity of antioxidant enzymes and ROS-scavenging ability. Despite the involvement of indole-3-acetic acid (IAA) in restricting FB1-induced PCD, feeding of IAN and I3C attenuated FB1-induced PCD in the IAA receptor mutant tir1-1 just as in Col-0. Taken together, our results indicate that TGG-catalyzed breakdown products of IGS decrease the accumulation of ROS by their antioxidant behavior, and attenuate FB1 induced PCD in an IAA-independent way.

Hypoxia regulates glutamate receptor trafficking through an HIF-independent mechanism.

Oxygen influences behaviour in many organisms, with low levels (hypoxia) having devastating consequences for neuron survival. How neurons respond physiologically to counter the effects of hypoxia is not fully understood. Here, we show that hypoxia regulates the trafficking of the glutamate receptor GLR-1 in C. elegans neurons. Either hypoxia or mutations in egl-9, a prolyl hydroxylase cellular oxygen sensor, result in the internalization of GLR-1, the reduction of glutamate-activated currents, and the depression of GLR-1-mediated behaviours. Surprisingly, hypoxia-inducible factor (HIF)-1, the canonical substrate of EGL-9, is not required for this effect. Instead, EGL-9 interacts with the Mint orthologue LIN-10, a mediator of GLR-1 membrane recycling, to promote LIN-10 subcellular localization in an oxygen-dependent manner. The observed effects of hypoxia and egl-9 mutations require the activity of the proline-directed CDK-5 kinase and the CDK-5 phosphorylation sites on LIN-10, suggesting that EGL-9 and CDK-5 compete in an oxygen-dependent manner to regulate LIN-10 activity and thus GLR-1 trafficking. Our findings demonstrate a novel mechanism by which neurons sense and respond to hypoxia.

Induction of ROS generation and NF-κB activation in MARC-145 cells by a novel porcine reproductive and respiratory syndrome virus in Southwest of China isolate.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of an economically important swine disease that has devastated the swine industry since the late 1980s. The aim of the present study was to investigate the interaction between reactive oxygen species (ROS) and NF-κB by PRRSV infection. RESULTS: We isolated the local strain of PRRSV from southwest China, designated YN-2011, then sequenced and analyzed the genome. YN-2011 was then used to evaluate the interaction of ROS and NF-κB. In PRRSV infected MARC-145 cells, there was a time-dependent increase in ROS and Maleic Dialdehyde (MDA). Accordingly, NF-κB activation was also increased as PRRSV infection progressed. Degradation of IκB mRNA was detected late in PRRSV infection, and overexpression of the dominant negative form of IκBα significantly suppressed NF-κB induced by PRRSV. CONCLUSIONS: The results indicate that the generation of ROS is involved in PRRSV replication and this progression is associated with the alteration in NF-κB activity induced by ROS. These results should extend our better understanding the interaction between PRRSV and host MARC-145 cells.

SPP-5 affects larval arrest via insulin signaling pathway in Caenorhabditis elegans.

Diapause is an endocrine-mediated metabolic and growth arrest state in response to unfavorable external environments. The nematode Caenorhabditis elegans can enter diapause/arrest during embryonic, larval, or adult stages when subjected to detrimental external environments. Larval stage 1 (L1) arrest happens when animals hatch without food. Previous work has shown that the insulin pathway plays a prominent role in regulating L1 arrest. However, the downstream signal molecular mechanisms and biomarkers are still missing. In this study, we showed that SaPosin-like Protein family member SPP-5 is significantly upregulated during L1 arrest, suggesting that it could act as an L1 arrest biomarker. Using RNA interference we demonstrated that spp-5  knockdown accelerated larval development, while the overexpression resulted in L1 arrest. Consistently, SPP-5 level was significantly up-regulated in the L1 arrest daf-2(e1370) mutants, and spp-5(RNAi) suppressed the daf-2(e1370) induced L1 arrest. These results suggest that SPP-5 can serve as an L1 arrest biomarker and promote the arrest probably via the insulin signaling pathway.

Cellular and Molecular Mechanisms Underlying Synaptic Subcellular Specificity.

Chemical synapses are essential for neuronal information storage and relay. The synaptic signal received or sent from spatially distinct subcellular compartments often generates different outcomes due to the distance or physical property difference. Therefore, the final output of postsynaptic neurons is determined not only by the type and intensity of synaptic inputs but also by the synaptic subcellular location. How synaptic subcellular specificity is determined has long been the focus of study in the neurodevelopment field. Genetic studies from invertebrates such as Caenorhabditis elegans (C. elegans) have uncovered important molecular and cellular mechanisms required for subcellular specificity. Interestingly, similar molecular mechanisms were found in the mammalian cerebellum, hippocampus, and cerebral cortex. This review summarizes the comprehensive advances in the cellular and molecular mechanisms underlying synaptic subcellular specificity, focusing on studies from C. elegans and rodents.

Water saving irrigation mediates bioactive pigments metabolism and storage capacity in tomato fruit.

Tomato fruit consumption is influenced by flavor and nutrient quality. In the present study, we investigate the impact of water saving irrigation (WSI) as a pre-harvest management on flavor and nutrient quality of tomato fruit. Our results demonstrate that WSI-treated tomato fruit exhibited improved sensory scores as assessed by a taste panel, accompanied by elevated levels of SlGLK2 expression, sugars, acids, and carotenoid contents compared to non-treated fruit. Notably, WSI treatment significantly enhanced the development of chloroplast and plastoglobulus in chromoplast, which served as carotenoid storage sites and upregulated the expression of carotenoid biosynthetic genes. Furthermore, integrated transcriptome and metabolome analysis revealed heightened expression of sugar and flavonoid metabolism pathways in WSI-treated tomato fruit. Remarkably, the master regulator SlMYB12 displayed a substantially increased expression due to WSI. These findings suggest that WSI is an effective and sustainable approach to enhance the pigments metabolism and storage capacity as well as the organoleptic characteristics and nutritional value of tomato fruit, offering a win-win solution for both water conservation and quality improvement in agro-food production.

Investigation of Prototheca bovis Infection and Its Correlation with Dairy Herd Improvement Data from a Dairy Farm in Central China.

Prototheca bovis (P. bovis), an alga that has attracted considerable attention over the years as a causative microorganism of mastitis in dairy cows, exhibits limited susceptibility to specific aminoglycosides and antifungal agents, and no effective clinical treatment is currently available, thereby posing challenges for both prevention and treatment. To investigate the infection of P. bovis mastitis and its impact on raw milk production, a total of 348 raw milk samples were collected from August to December 2022 from a dairy farm in central China. P. bovis and other bacteria were detected, and the average infection rate of P. bovis in raw milk was 60.34% (210/348). The total number of colonies and the somatic cell count (SCC) of P. bovis positive samples were significantly higher than those of P. bovis negative samples (p < 0.01). The daily milk yield, 305-day milk yield, peak milk yield, and days to peak milk yield of the P. bovis positive samples were significantly lower than those of P. bovis negative samples (p < 0.01). A correlation analysis showed that P. bovis infection was negatively correlated with daily milk yield, 305-day milk yield, peak milk yield, and days to peak milk yield (p < 0.0001), while being positively correlated with the total number of colonies, SCC, milk loss, and protein percentage (p < 0.0001). These findings may help practitioners in comprehending the occurrence of Prototheca mastitis and developing more effective strategies for the prevention of P. bovis infections.

Effect of the VR-guided grasping task on the brain functional network.

Virtual reality (VR) technology has been demonstrated to be effective in rehabilitation training with the assistance of VR games, but its impact on brain functional networks remains unclear. In this study, we used functional near-infrared spectroscopy imaging to examine the brain hemodynamic signals from 18 healthy participants during rest and grasping tasks with and without VR game intervention. We calculated and compared the graph theory-based topological properties of the brain networks using phase locking values (PLV). The results revealed significant differences in the brain network properties when VR games were introduced compared to the resting state. Specifically, for the VR-guided grasping task, the modularity of the brain network was significantly higher than the resting state, and the average clustering coefficient of the motor cortex was significantly lower compared to that of the resting state and the simple grasping task. Correlation analyses showed that a higher clustering coefficient, local efficiency, and modularity were associated with better game performance during VR game participation. This study demonstrates that a VR game task intervention can better modulate the brain functional network compared to simple grasping movements and may be more beneficial for the recovery of grasping abilities in post-stroke patients with hand paralysis.

Enhancing post-harvest quality of tomato fruits with chitosan oligosaccharide-zinc oxide nanocomposites: A study on biocompatibility, quality improvement, and carotenoid enhancement.

In this study, a new composite with combination of chitosan oligosaccharide (COS) and zinc oxide nanoparticles (ZnO NPs), termed Chitosan Oligosaccharide-Zinc Oxide Nanocomposites (COS-ZnO NC), was designed to enhance the quality of tomato fruits during postharvest storage. SEM analysis showed a uniform distribution of COS-ZnO NC films on tomato surfaces, indicating high biocompatibility, while the FTIR spectrum confirmed the interaction of COS and ZnO NPs via hydrogen bonds. The COS-ZnO NC exerts positive effects on post-harvest quality of tomato fruits, including significantly reduced water loss, fewer skin wrinkles, increased sugar-acid ratio, and enhanced vitamin C and carotenoids accumulation. Furthermore, COS-ZnO NC induces transcription of carotenoid biosynthesis genes and promotes carotenoids storage in the chromoplast. These results suggest that the COS-ZnO NC film can significantly improve the quality traits of tomato fruits, and therefore is potential in post-harvest storage of tomato fruits.

One-day thermal regime extends the lifespan in Caenorhabditis elegans.

Environmental factors, including temperature, can modulate an animal's lifespan. However, their underlying mechanisms remain largely undefined. We observed a profound effect of temperature on the aging of Caenorhabditis elegans (C. elegans) by performing proteomic analysis at different time points (young adult, middle age, and old age) and temperature conditions (20 °C and 25 °C). Importantly, although at the higher temperature, animals had short life spans, the shift from 20 °C to 25 °C for one day during early adulthood was beneficial for protein homeostasis since; it decreased protein synthesis and increased degradation. Consistent with our findings, animals who lived longer in the 25 °C shift were also more resistant to high temperatures along with oxidative and UV stresses. Furthermore, the lifespan extension by the 25 °C shift was mediated by three important transcription factors, namely FOXO/DAF-16, HSF-1, and HIF-1. We revealed an unexpected and complicated mechanism underlying the effects of temperature on aging, which could potentially aid in developing strategies to treat age-related diseases. Our data are available in ProteomeXchange with the identifier PXD024916.