Search

To confirm the seabed fluid flow at the Haima cold seeps, an integrated study of multi-beam and seismic data reveals the morphology and fate of four bubble plumes and investigates the detailed subsurface structure of the active seepage area. The shapes of bubble plumes are not constant and influenced by the northeastward bottom currents, but the water depth where these bubble plumes disappear (630–650 m below the sea level) (mbsl) is very close to the upper limit of the gas hydrate stability zone in the water column (620 m below the sea level), as calculated from the CTD data within the study area, supporting the “hydrate skin” hypothesis. Gas chimneys directly below the bottom simulating reflectors, found at most sites, are speculated as essential pathways for both thermogenic gas and biogenic gas migrating from deep formations to the gas hydrate stability zone. The fracture network on the top of the basement uplift may be heavily gas-charged, which accounts for the chimney with several kilometers in diameter (beneath Plumes B and C). The much smaller gas chimney (beneath Plume D) may stem from gas saturated localized strong permeability zone. High-resolution seismic profiles reveal pipe-like structures, characterized by stacked localized amplitude anomalies, just beneath all the plumes, which act as the fluid conduits conveying gas from the gas hydrate-bearing sediments to the seafloor, feeding the gas plumes. The differences between these pipe-like structures indicate the dynamic process of gas seepage, which may be controlled by the build-up and dissipation of pore pressure. The 3D seismic data show high saturated gas hydrates with high RMS amplitude tend to cluster on the periphery of the gas chimney. Understanding the fluid migration and hydrate accumulation pattern of the Haima cold seeps can aid in the further exploration and study on the dynamic gas hydrate system in the South China Sea.

In this paper we study derived categories of nodal singularities. We show that for all nodal singularities there is a categorical resolution whose kernel is generated by a $2$ or $3$-spherical object, depending on the dimension. We apply this result to the case of nodal cubic fourfolds, where we describe the kernel generator of the categorical resolution as an object in the bounded derived category of the associated degree six K3 surface. This paper originated from one of the problem sessions at the Interactive Workshop and Hausdorff School "Hyperk\"ahler Geometry", Bonn, September 6-10, 2021., Comment: 30 pages, final version to appear in Rendiconti del Circolo Matematico di Palermo Series 2

Previous studies of gas hydrate in the Dongsha area mainly focused on the deep-seated gas hydrates that have a high energy potential, but cared little about the shallow gas hydrates occurrences. Shallow gas hydrates have been confirmed by drill cores at three sites (GMGS2 08, GMGS2 09 and GMGS2 16) during the GMGS2 cruise, which occur as veins, blocky nodules or massive layers, at 8–30 m below the seafloor. Gas chimneys and faults observed on the seismic sections are the two main fluid migration pathways. The deep-seated gas hydrate and the shallow hydrate-bearing sediments are two main seals for the migrating gas. The occurrences of shallow gas hydrates are mainly controlled by the migration of fluid along shallow faults and the presence of deep-seated gas hydrates. Active gas leakage is taking place at a relatively high-flux state through the vent structures identified on the geophysical data at the seafloor, although without resulting in gas plumes easily detectable by acoustic methods. The presence of strong reflections on the high-resolution seismic profiles and dim or chaotic layers in the sub-bottom profiles are most likely good indicators of shallow gas hydrates in the Dongsha area. Active cold seeps, indicated by either gas plume or seepage vent, can also be used as indicators for neighboring shallow gas hydrates and the gas hydrate system that is highly dynamic in the Dongsha area.

In this paper, we prove a Clifford type inequality for the curve $X_{2,2,2,4}$, which is the intersection of a quartic and three general quadratics in $\mathbb{P}^5$. We thus prove a stronger Bogomolov-Gieseker inequality for characters of stable vector bundles and stable objects on $X_{2,4}$. Applying the scheme proposed by Bayer, Bertram, Macr\`i, Stellari and Toda, we can construct an open subset of Bridgeland stability conditions on $X_{2,4}$., Comment: Change the structure of the paper to make it more readable. No mathematical changes. Correct typos. Update reference. Update introduction. Prejournal version. To be published on Forum of Mathematics, Sigma. 33 pages, 3 figures, comments are very welcome! arXiv admin note: text overlap with arXiv:1810.03434 by other authors

Keloids, as a result of abnormal wound healing in susceptible individuals, are characterized by the hyper-proliferation of fibroblasts and exaggerated deposition of extracellular matrix. Current surgical and therapeutic modalities provide limited satisfactory results. Growing evidence has highlighted the roles of circRNAs in acting as miRNA sponges. However, up to date, the regulatory mechanism of circRNAs in the pathological process of keloids has rarely been reported. In this study, cell proliferation, cell migration, flow cytometry, western blotting, fluorescence in situ hybridization, dual-luciferase activity, and immunohistochemistry assays were applied to explore the roles and mechanisms of the circCOL5A1/miR-7-5p/Epac1 axis in the keloid. The therapeutic potential of circCOL5A1 was investigated by establishing keloid implantation models. The RT-qPCR result revealed that circCOL5A1 expression was obviously higher in keloid tissues and keloid fibroblasts. Subsequent cellular experiments demonstrated that circCOL5A1 knockdown repressed the proliferation, migration, extracellular matrix (ECM) deposition, whereas promoted cell apoptosis, through the PI3K/Akt signaling pathway. Furthermore, RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that both circCOL5A1 and miR-7-5p were located in the cytoplasm. The luciferase reporter gene assay confirmed that exact binding sites were present between circCOL5A1 and miR-7-5p, as well as between miR-7-5p and Epac1. Collectively, the present study revealed that circCOL5A1 functioned as competing endogenous RNA (ceRNA) by adsorbing miR-7-5p to release Epac1, which contributed to pathological hyperplasia of keloids through activating the PI3K/Akt signaling pathway. Our data indicated that circCOL5A1 might serve as a novel promising therapeutic target and represent a new avenue to understand underlying pathogenesis for keloids.

Regulation of tuber dormancy and sprouting are pivotal for postharvest storage, sales, and seed breeding of potatoes (Solanum tuberosum L.). Nitrogen is an essential mineral nutrient required in potato production, which directly influences tuber development and quality. However, the effects of nitrogen on the post-harvest dormancy of potato tubers remain unclear, and their association with the initial tuber development are poorly understood. The aim of this study was to clarify the effects of nitrogen application rate on potato tuber dormancy and the associated physiological mechanisms. We obtained the tubers of different commercial potato cultivars (E shu3, Z shu5, and H shu3) at three nitrogen levels (0, 210, and 315 kg N ha−1) through field experiment, and then stored the tubers at room temperature (25 ℃) in the dark for 0–16 weeks. The dormancy period and alkaloid accumulation of potato tubers were analyzed, and the quality of seed tubers was evaluated by examining eye sprouting and replanting. We also conducted a pot experiment to explore the differences in tuber and stolen development of one potato cultivar (H shu3) at the three nitrogen levels. The carbohydrate and phytohormone contents in the apical bud meristem of dormant tubers and the enlarged subapical region of stolons were measured. The results showed that a reduction in the nitrogen application rate extended the dormancy period of potato tubers by 3–6 weeks and thereby reduced the risk of alkaloid accumulation caused by tuber sprouting, which was favorable for potato storage and sales. From the perspective of seed potato breeding, nitrogen application markedly increased the number of sprouting eyes, resulting in more stems and higher tuber yield after replanting. Compared to the control, nitrogen application promoted the sprouting of eyes at the apical bud of potato tubers, improved associated α-amylase activity and sucrose content, and increased gibberellin 1 (GA 1) content by 6.0 times. Nitrogen application also facilitated stolon elongation and growth, increased associated GA 1 content by 2.2 times, and delayed the enlargement of the subapical region to form tubers by 6–15 d. Taken together, the results indicate that nitrogen management (increasing or reducing nitrogen application rate) can be used as an agricultural practice to regulate potato tuber dormancy and sprouting. The intrinsic link between regulation of tuber dormancy by nitrogen application rate and its effects on tuber development is attributable to the regulation of tuberization. This research provides abundant physiological information for tuber dormancy and development in potatoes.

Background A keloid is a type of pathological scar often caused by abnormal tissue repair after a skin injury and is more common in genetically susceptible individuals. cAMP is a universal second messenger and regulates critical physiological processes, including calcium homeostasis, secretion, cell fate, and gene transcription, by affecting the expression of the exchange protein directly activated by cAMP (Epac). Epac has two isoforms, Epac1 (cAMP-GEF-1) and Epac2 (cAMP-GEF-II), which show varying expression levels depending on the tissue and cell type. The expression of Epac1 in keloids has not yet been investigated. Materials and methods Keloid tissue and normal dermal skin tissue were analyzed by hematoxylin and eosin staining and immunofluorescence. Primary human keloid fibroblasts (HKFs) and human normal dermal fibroblasts were studied using immunofluorescence, wound healing tests, reverse transcription polymerase chain reaction, and western blot analysis with different concentrations of the Epac1 inhibitor ESI-09. Results Downregulation of Epac was performed using ESI-09, a specific Epac inhibitor. The proliferation and migration capacities of HKFs and human normal dermal fibroblasts showed an ESI-09 concentration-dependent decrease. Furthermore, the apoptosis rates were significantly different between fibroblasts treated with ESI-09 and control fibroblasts. In addition, the phosphorylation level of Akt was significantly decreased, indicating that ESI-09 reduces fibrosis and induces apoptosis through Akt signaling in HKFs. Conclusions Our results illustrate the role of Epac1 in regulating fibroblast function during keloid pathogenesis and indicate that Epac1 may be a potential therapeutic target in keloid treatment.

Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion. We also found both motifs prevent TRAF5 and TRAF6, the MAVS downstream adaptors, to be recruited to MAVS, while the motif 39-KEALSDGI-46 also blocks TRAF3 migrating to MAVS. In parallel, these TRAFs are important in activating transcription factors NF-kB and/or IRF-3 by hMPV. Our findings collectively demonstrate that M2-2 uses its PDZ motifs to launch the hMPV immune evasion through blocking the interaction of MAVS and its downstream TRAFs.

Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in young children and high-risk adults. However, a specific treatment for this viral infection is not currently available. In this study, we discovered that an exchange protein directly activated by cyclic AMP (EPAC) can serve as a potential therapeutic target for RSV. In both lower and upper epithelial cells, treatment with EPAC inhibitor (ESI-09), but not protein kinase A inhibitor (H89), significantly inhibits RSV replication and proinflammatory cytokine/chemokine induction. In addition, RSV-activated transcriptional factors belonging to the NF-κB and IRF families are also suppressed by ESI-09. Through isoform-specific gene knockdown, we found that EPAC2, but not EPAC1, plays a dominant role in controlling RSV replication and virus-induced host responses. Experiments using both EPAC2 knockout and EPAC2-specific inhibitor support such roles of EPAC2. Therefore, EPAC2 is a promising therapeutic target to regulate RSV replication and associated inflammation. IMPORTANCE RSV is a serious public health problem, as it is associated with bronchiolitis, pneumonia, and asthma exacerbations. Currently no effective treatment or vaccine is available, and many molecular mechanisms regarding RSV-induced lung disease are still significantly unknown. This project aims to elucidate an important and novel function of a protein, called EPAC2, in RSV replication and innate inflammatory responses. Our results should provide an important insight into the development of new pharmacologic strategies against RSV infection, thereby reducing RSV-associated morbidity and mortality.

Chronic exposure to environmental heavy metals is a worldwide health concern. It is acknowledged to be an important cause of lower respiratory tract damage in children. However, the molecular mechanisms underlying the heavy metal-induced cellular stress/toxicity are not completely understood. Small non-coding RNAs (sncRNAs), such as microRNAs (miRNA) and more recently identified tRNA-derived RNA fragments (tRFs), are critical to the posttranscriptional control of genes. We used deep sequencing to investigate whether cellular sncRNA profiles are changed by environmental heavy metals. We found that the treatment of arsenite, an important groundwater heavy metal, leads to abundant production of tRFs, that are ~30 nucleotides (nts) long and most of which correspond to the 5′-end of mature tRNAs. It is unlikely for these tRFs to be random degradation by-products, as the type of induced tRFs is heavy metal-dependent. Three most inducible tRFs and their roles in arsenite-induced cellular responses were then investigated. We identified that p65, an important transcription factor belonging to NF-κB family and also a key factor controlling inflammatory gene expression, is a regulated target of a tRF derived from 5′-end of mature tRNA encoding AlaCGC (tRF5-AlaCGC). tRF5-AlaCGC activates p65, subsequently leading to enhanced secretion of IL-8 in arsenite response. In this study, we also identified that endonuclease Dicer and angiogenin temporally control the induction of tRF5-AlaCGC, providing an insight into the control of tRF biogenesis and subsequently the prevention of cellular damage.

Respiratory syncytial virus (RSV) is a single-stranded, negative-strand RNA virus belonging to Paramyxoviridae family, and is in the genus Pneumovirus. It was discovered in chimpanzees in 1955 and subsequently confirmed to be a human pathogen shortly after that. RSV is one of the most common viruses to infect young children and high-risk adults worldwide, and the leading cause of inflammation of the lungs (pneumonia) or the lungs’ airways (bronchiolitis) in infants. Due in part to the lack of long-term immunity after infection, making reinfection frequent. There is a single antiviral treatment for RSV currently approved, but its use is limited by questionable efficacy, side effects, and cost, and it is recommended that it be used only for patients at-risk for severe disease, on a case-by-case basis. In this study, we discovered an exchange protein directly activated by cyclic AMP (EPAC) that can serve as a potential therapeutic target for RSV. In both lower and upper epithelial cells, the treatment of EPAC inhibitor (ESI-09), but not PKA inhibitor (H89), significantly inhibits the RSV replication and pro-inflammatory cytokine/chemokine induction. In addition, RSV-activated transcriptional factors belonging to the NF-κB and IRF families are also suppressed by ESI-09. Through isoform-specific gene knock down, we found that EPAC2, but not EPAC1, plays a dominant role in controlling RSV replication and viral-induced host responses. Experiments using both EPAC2 knock out and EPAC2 specific inhibitor support such roles of EPAC2. Therefore, EPAC2 could be a promising therapeutic target to regulate RSV replication and associated inflammation.