Mapping and placemaking from the perspective of cultural field

Recently, in the context of China's policy of vigorously developing the assertive culture confidence, the value of traditional culture has been re-recognized by the whole society. However, due to the unbalanced development of China's eastern and western regions, the value of cultural heritage is not valued in the western region. Hanzhong district in Shaanxi province, belonging to the intersection of the south and north, has its own unique natural and cultural environment. The three historic sites of the western Han Dynasty are located in the city centre of Hanzhong, and as the historical heritage of Han culture, it has been hesitant between protection and development for many years. On the one hand, this paper tries to introduce the concept of "field" into the protection of cultural heritage, by constructing the cultural field model and using the cultural field to explore the question of historical heritage activation. This article, on the other hand, by expanding the mapping function, using the method of mapping defined the three historic sites of the western Han dynasty culture field research scope and the elements, combing extracted place identity, controlling the space boundary of place and for placemaking, and proposing an operable strategy and approach

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional profiling of E7-expressing cells

The E7 oncoprotein of the high-risk human papillomavirus (HPV) plays a major role in HPV-induced carcinogenesis. E7 abrogates the G(1) cell cycle checkpoint and induces genomic instability, but the mechanism is not fully understood. In this study, we performed RNA sequencing (RNA-seq) to characterize the transcriptional profile of keratinocytes expressing HPV 16 (HPV-16) E7. At the transcriptome level, 236 genes were differentially expressed between E7 and vector control cells. A subset of the differentially expressed genes, most of them novel to E7-expressing cells, was further confirmed by real-time PCR. Of interest, the activities of multiple transcription factors were altered in E7-expressing cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were investigated. The upregulated genes were enriched in cell cycle and DNA replication, as well as in the DNA metabolic process, transcription, DNA damage, DNA repair, and nucleotide metabolism. Specifically, we focused our studies on the gene encoding WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein), one of the genes that was upregulated in E7-expressing cells. WDHD1 is a component of the replisome that regulates DNA replication. Recent studies suggest that WDHD1 may also function as a DNA replication initiation factor as well as a G(1) checkpoint regulator. We found that in E7-expressing cells, the steady-state level of WDHD1 protein was increased along with the half-life. Moreover, downregulation of WDHD1 reduced E7-induced G(1) checkpoint abrogation and rereplication, demonstrating a novel function for WDHD1. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications. IMPORTANCE The high-risk HPV types induce cervical cancer and encode an E7 oncoprotein that plays a major role in HPV-induced carcinogenesis. However, the mechanism by which E7 induces carcinogenesis is not fully understood; specific anti-HPV agents are not available. In this study, we performed RNA-seq to characterize transcriptional profiling of keratinocytes expressing HPV-16 E7 and identified more than 200 genes that were differentially expressed between E7 and vector control cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were identified. Significantly, the WDHD1 gene, one of the genes that is upregulated in E7-expressing cells, was found to play an important role in E7-induced G(1) checkpoint abrogation and rereplication. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications

Effects of crabs on greenhouse gas emissions, soil nutrients, and stoichiometry in a subtropical estuarine wetland 260 __

Crabs may elicit effects on wetland carbon (C), nitrogen (N), and phosphorus (P) concentrations and associated ecological stoichiometry. In this study, we assessed effects of crabs on carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) emissions; soil C, N, and P concentrations; and stoichiometry in upper and mid-tidal flats of an estuarine wetland in China. The results showed that averaged CO2, CH4, and N2O fluxes were greater in the upper and mid-tidal flats in the presence of crabs, being 46.4, 66.7, and 69.7% and 53.6, 143, and 73.1% greater than control, respectively. Mixed model analyses showed overall positive relationships between wetland soil CO2 CH4 and N2O emissions (F = 4.65, P = 0.033; F = 42.42, P = 0.042 and F = 10.2, P = 0.0018, respectively) in the presence of crabs, taking into account season, flooding intensity, and plot effects. This may be related to the direct effects of respiration and the indirect effects of feeding, excretion, and disturbance of soil on microorganisms and/or plant roots. There were no effects of crabs on total C or N concentrations, whereas decreased soil total P concentrations, especially in the upper-tidal flats (P = 0.04). Crab presence was positively associated with soil C/P and N/P ratios (P < 0.0001 and P < 0.0001, respectively), taking into account season, flooding intensity, and plot effects. In the upper and mid-tidal flats, soil CO2 emissions were negatively correlated with total soil C; CH4 emissions were positively correlated with ratios of C/N and C/P; and N2O emissions were positively correlated with N content. In general, global warming potential (GWP) of the upper-tidal flats in the presence of crabs increased by 138% compared with the absence of crabs, and GWP of the mid-tidal flats in the presence of crabs increased by 99.3% compared with the absence of crabs. Global warming and associated flooding rise in several coastal wetland areas are favoring benthic fauna number enhancement, and this in turn increases GWP of overall gas emissions further contributing to future warming rise

Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus

Apoptotic cells are considered to be a major source for autoantigens in autoimmune diseases such as systemic lupus erythematosus (SLE). In agreement with this, defective clearance of apoptotic cells has been shown to increase disease susceptibility. Still, little is known about how apoptotic cell–derived self-antigens activate autoreactive B cells and where this takes place. In this study, we find that apoptotic cells are taken up by specific scavenger receptors expressed on macrophages in the splenic marginal zone and that mice deficient in these receptors have a lower threshold for autoantibody responses. Furthermore, antibodies against scavenger receptors are found before the onset of clinical symptoms in SLE-prone mice, and they are also found in diagnosed SLE patients. Our findings describe a novel mechanism where autoantibodies toward scavenger receptors can alter the response to apoptotic cells, affect tolerance, and thus promote disease progression. Because the autoantibodies can be detected before onset of disease in mice, they could have predictive value as early indicators of SLE

Nocaviogua A and B: two lipolanthines from root-nodule-associated Nocardia sp.

Nocaviogua A (1) and B (2), two lipolanthines featuring a non-canonical avionin (Avi)-containing macrocycle and a long acyl chain, were identified from the mutualistic actinomycete Nocardia sp. XZ19_369, which was isolated from the nodules of sea buckthorn collected in Tibet. Their planar structures were elucidated via extensive analyses of 1D and 2D NMR, as well as HRMS data. The absolute configurations were fully elucidated by advanced Marfey’s analysis and GIAO NMR calculations, representing the first time that the configurations of this family of lipolanthines have been determined. Nocaviogua A (1) exhibited weak cytotoxicity against human chronic uveal melanoma cells (UM92-1), non-small cell lung cancer (NCI-H2170), and breast cancer (MDA-MB-231). Our work provides valuable information on this burgeoning class of lipolanthines for further investigations

Pulmonary exposure to single-walled carbon nanotubes does not affect the early immune response against Toxoplasma gondii

Background Single-walled carbon nanotubes (SWCNT) trigger pronounced inflammation and fibrosis in the lungs of mice following administration via pharyngeal aspiration or inhalation. Human exposure to SWCNT in an occupational setting may occur in conjunction with infections and this could yield enhanced or suppressed responses to the offending agent. Here, we studied whether the sequential exposure to SWCNT via pharyngeal aspiration and infection of mice with the ubiquitous intracellular parasite Toxoplasma gondii would impact on the immune response of the host against the parasite. Methods C57BL/6 mice were pre-exposed by pharyngeal administration of SWCNT (80 + 80 μg/mouse) for two consecutive days followed by intravenous injection with either 1x103 or 1x104 green fluorescence protein and luciferase-expressing T. gondii tachyzoites. The dissemination of T. gondii was monitored by in vivobioluminescence imaging in real time for 7 days and by plaque formation. The inflammatory response was analysed in bronchoalveolar lavage (BAL) fluid, and by assessment of morphological changes and immune responses in lung and spleen. Results There were no differences in parasite distribution between mice only inoculated with T. gondii or those mice pre-exposed for 2 days to SWCNT before parasite inoculum. Lung and spleen histology and inflammation markers in BAL fluid reflected the effects of SWCNT exposure and T. gondii injection, respectively. We also noted that CD11c positive dendritic cells but not F4/80 positive macrophages retained SWCNT in the lungs 9 days after pharyngeal aspiration. However, co-localization of T. gondii with CD11c or F4/80 positive cells could not be observed in lungs or spleen. Pre-exposure to SWCNT did not affect the splenocyte response to T. gondii. Conclusions Taken together, our data indicate that pre-exposure to SWCNT does not enhance or suppress the early immune response to T. gondii in mice

Mutational Profile and Potential Molecular Therapeutic Targets of Pheochromocytoma

PurposePheochromocytoma/paraganglioma (PCC/PGL; collectively known as PPGL) can be driven by germline and somatic mutations in susceptibility genes. We aimed to investigate the mutation profile and clinical features of pathogenic genes in highly genetically heterogeneous PPGL and to preliminary explore molecular therapeutic targets in PPGL.MethodsWe established a panel of 260 genes, including susceptibility genes of PPGL and other important tumorigenic genes to sequence 107 PPGL tissues.ResultsOverall, 608 genomic mutations were identified in 107 PPGL tissues. Almost 57% of PPGL tissue samples exhibited pathogenic mutations, and the most frequently mutated gene was SDHB (15/107, 14%). SDHB and HRAS were the most commonly mutated genes in germline-mutated PPGL (25/107, 23%) and nongermline-mutated PPGL (36/107, 34%), respectively. In addition, novel pathogenic mutations were detected in sporadic PPGL. PPGL with mutations in the hypoxia pathway had an earlier onset and higher norepinephrine level than those in the kinase pathway. Receptor tyrosine kinase (RTK; 22%, 24/107), mitogen-activated protein kinase (MAPK; 14%, 15/107), and tyrosine kinase (TK; 2%, 2/107) pathways were the most frequently mutated pathways in PPGL.ConclusionOur results provided the genetic mutation profile in PPGL tissues. Genetic mutations in PPGL were mainly concentrated in the RTK, TK, and MAPK pathways, suggesting potential molecular therapeutic targets for PPGL

Structural and Functional Insights into an Archaeal Lipid Synthase

The UbiA superfamily of intramembrane prenyltransferases catalyzes an isoprenyl transfer reaction in the biosynthesis of lipophilic compounds involved in cellular physiological processes. Digeranylgeranylglyceryl phosphate (DGGGP) synthase (DGGGPase) generates unique membrane core lipids for the formation of the ether bond between the glycerol moiety and the alkyl chains in archaea and has been confirmed to be a member of the UbiA superfamily. Here, the crystal structure is reported to exhibit nine transmembrane helices along with a large lateral opening covered by a cytosolic cap domain and a unique substrate-binding central cavity. Notably, the lipid-bound states of this enzyme demonstrate that the putative substrate-binding pocket is occupied by the lipidic molecules used for crystallization, indicating the binding mode of hydrophobic substrates. Collectively, these structural and functional studies provide not only an understanding of lipid biosynthesis by substrate-specific lipid-modifying enzymes but also insights into the mechanisms of lipid membrane remodeling and adaptation