Alternative splicing generates differing RNA isoforms that govern phenotypic complexity of eukaryotes. Its malfunction underlies many diseases, including cancer and cardiovascular diseases. ...Comparative analysis of RNA isoforms at the genome-wide scale has been difficult. Here, we establish an experimental and computational pipeline that performs de novo transcript annotation and accurately quantifies transcript isoforms from cDNA sequences with a full-length isoform detection accuracy of 97.6%. We generate a searchable, quantitative human transcriptome annotation with 31,025 known and 5,740 novel transcript isoforms ( http://steinmetzlab.embl.de/iBrowser/ ). By analyzing the isoforms in the presence of RNA Binding Motif Protein 20 (RBM20) mutations associated with aggressive dilated cardiomyopathy (DCM), we identify 121 differentially expressed transcript isoforms in 107 cardiac genes. Our approach enables quantitative dissection of complex transcript architecture instead of mere identification of inclusion or exclusion of individual exons, as exemplified by the discovery of IMMT isoforms mis-spliced by RBM20 mutations. Thereby we achieve a path to direct differential expression testing independent of an existing annotation of transcript isoforms, providing more immediate biological interpretation and higher resolution transcriptome comparisons.
Abstract High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative ...vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It’s essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV.
Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian carcinoma (EOC). We conducted this research to investigate the clinical characteristics and outcomes of OCCC ...and to provide additional supporting evidence to aid in the clinical diagnosis and management.
This was a retrospective study investigating the clinical characteristics and survival outcomes of 86 patients with OCCC treated at our center between January 2010 and March 2020. Survival analysis was also performed on 179 patients with OCCC obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registry database.
The median age of participants was 49.21 ± 9.91 years old, and 74.42% of them were diagnosed at early stage. The median CA125 level was 601.48 IU/mL, while 19.77% of the patients had normal CA125 levels. Sixteen patients (18.60%) had co-existing endometriosis and 8 patients (9.3%) developed venous thromboembolism (VTE). There were 5 patients received suboptimal cytoreduction. Sixty-six patients (76.74%) underwent lymphadenectomy, and only 3 (4.55%) patients had positive lymph nodes. Patients diagnosed at an early stage had higher 3-year overall survival (OS) and progression-free survival (PFS) rates than those with advanced stage OCCC. CA19-9 (P = 0.025) and ascites (P = 0.001) were significantly associated with OS, while HE4 (P = 0.027) and ascites (P = 0.001) were significantly associated with PFS. Analysis of data from the SEER database showed that positive lymph nodes is also an independent prognostic factor for OS (P = 0.001).
OCCC often presents at an early stage and young age with a mildly elevated CA125. CA19-9, HE4, massive ascites, and positive lymph node are independent prognostic factors.
The paper describes from a statistical perspective the diameter-dependence tensile strength and Young’s modulus in 40 sisal fibres samples. The fibres tensile properties depend significantly upon ...their diameter, which has been determined using optical and SEM microscope techniques. Further characterisation of the sisal fibres has been carried out using FT-IR and DSC techniques. The fibres’ ultimate tensile strength and Young’s modulus have been evaluated using four different estimation methods from two and three-parameter Weibull distribution statistics. We show the significant sensitivity of the Weibull predictions versus the number of fibres samples used in the distributions, with the Weibull modulus mσ obtained from our results being 10% smaller compared to what is reported in open literature. The scatter of the mechanical properties of the sisal fibres shown in this work is also compared to analogous distributions present in other works.
•Carbon (C) fixation and allocation was examined using in situ 13C pulse-labeling.•Moderate nitrogen (N) addition promoted photosynthetic C assimilation and fixation.•With increasing N addition, more ...C was allocated to roots.•Moderate N addition increased plant non-structural carbohydrates (NSC).•Existed a trade-off between the allocation C to defense and to storage and growth.
Atmospheric nitrogen (N) deposition is sharply increasing, and this may have substantial impact on carbon (C) fixation and allocation of plants. Knowledge of the effect of N addition on C fixation and allocation patterns of assimilated C is therefore critical to understand the effects on C cycles in terrestrial ecosystems. We conducted a field experiment to examine the effects of N addition (0 to 25 g N m−2 yr−1) on photosynthetic C fixation and C allocation by Leymus chinensis using 13CO2 pulse-labeling and measurements of the percentage of assimilation allocated to nonstructural carbohydrates (NSCs), secondary metabolites (SMs), and growth in a temperate semi-arid grassland. Moderate N addition (5 and 10 g N m−2 yr−1) significantly increased the δ13C value and 13C fixation of plant leaves by increasing Pn and biomass of L. chinensis. However, high N addition (25 g N m−2 yr−1) did not result in a further increase in Pn and total biomass, suggesting excess N inputs was harmful to photosynthetic C fixation in plants. Moderate N addition (10 g N m−2 yr−1) also significantly increased the root/shoot ratio and the proportion of assimilated 13C allocated to roots, but decreased the proportion of leaves and stems allocated, indicating more C was allocated to roots with N addition. We further found that moderate N addition increased the overall NSC and SM concentrations, but C allocation to growth decreased with increasing N, possibly indicating the existence of a trade-off between the C allocation to defense and the allocation to storage and growth. Our findings demonstrated that N addition will alter photosynthetic C fixation and the allocation patterns of photoassimilates, and thus will significantly affect the C cycle and C balance of terrestrial ecosystems under predicted future global changes.
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•The trade-offs between the ecosystem service supplies were increasing.•The correlations between the demands for ecosystem services were generally weak.•The spatial imbalance in ...supply-demand of grass production was obvious.•Urban areas have high demand of water yield and carbon sequestration services.•The strong wind has increased the demand for windbreaks and sand fixation service.
Assessing the relationships between ecosystem services supply and demand is crucial to support sustainable planning and human well-being. In the present study, we analyzed the ecosystem services supply and demand, synergies and trade-offs among services, as well as the spatial relationships between supply and demand, for four services in a desert steppe of Inner Mongolia. In terms of the balance between supply and demand, the grass production and carbon stock supply exceeded the demand, whereas the demand of water yield and windbreak and sand fixation services surpassed the supply. The degree of demand in windbreak and sand fixation service was met increased from 14.7% in 2000 to 20.6% in 2017, versus a decrease from 18.0% to 8.2% in water yield. The spatial distributions of the water yield and carbon stock demand were similar, and there was a significant synergy between them. The grass production supply and demand were not spatially matched, with higher supply in the eastern part of the study area and higher demand in the western part. Areas with high demand for the windbreak and sand fixation service also had a high supply. The water supply and demand in the low-coverage grassland were relatively balanced, and the deficiency of carbon stock supply was mainly found in construction land. In summary, for the sustainable development of animal husbandry and to reduce wind erosion, each county should establish an appropriate livestock density standard based on local constraints. Furthermore, it is also crucial for policymakers to develop water-saving industries to improve water utilization efficiency, and to set targets for CO2 emissions to reduce the impact on climate change.
Abstract Accumulating evidence suggests that caspase-3 plays critical roles beyond apoptosis, serving pro-survival functions in malignant transformation and tumorigenesis. However, the mechanism of ...non-apoptotic action of caspase-3 in oncogenic transformation remains unclear. In the present study, we show that caspase-3 is consistently activated in malignant transformation induced by exogenous expression of oncogenic cocktail (c-Myc, p53DD, Oct-4, and H-Ras) in vitro as well as in the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mouse model of breast cancer. Genetic ablation of caspase-3 significantly attenuated oncogene-induced transformation of mammalian cells and delayed breast cancer progression in MMTV-PyMT transgenic mice. Mechanistically, active caspase-3 triggers the translocation of endonuclease G (EndoG) from mitochondria, which migrates to the nucleus, thereby induces phosphorylation of Src-STAT3 signaling pathway to facilitate oncogenic transformation. Taken together, our data suggest that caspase-3 plays pivotal role in facilitating rather than suppressing oncogene-induced malignant transformation of mammalian cells.
This study examines the 22-year development of the Shanghai Biennale from a localized contemporary art exhibition to an internationally renowned art biennale. Through the lens of organizational ...legitimacy, this research examines how the Shanghai Biennale negotiated changing external pressures to establish within China and grow into the international art world. Using a mix-methods approach, we first create a unique database of participant nationality and then examine artist and curatorial statements, media reports, and interviews with organizers and curators of the Shanghai Biennale from 1996 to 2018. Our study delineates three periods of the Shanghai Biennale’s development: incipient (1996–1998), internationalization (2000–2010), and expanding period (2012–2018). Through these periods we examine the different pathways by which the Shanghai Biennale attained legitimacy first within the local and national Chinese context and then within the Biennale’s expansion into the international art scene. We find at the beginning stage of the Shanghai Biennale, establishing local legitimacy was the foremost concern. When the Shanghai Biennale started to diffuse into the global art world in 2000, focus shifted towards remaking the Shanghai Biennale to comply with international perceptions. That said, our research finds both local and international legitimacy requirements remained salient simultaneously, with the importance of maintaining a good relationship with the Chinese State as a critical basis for internationalization and development. In the most recent editions, more local and non-Western features are included in the Shanghai Biennale, signaling the Biennale’s efforts of distinguishing itself in the global biennale scene. This research contributes to organizational study by closely examining a cultural organization’s ability to negotiate legitimacy requirements in different contexts, but also empirically responds to recent calls for studies on the global development of non-Western biennales.
Grazing is an important land use in northern China. In general, different grazing intensities had a different impact on the morphological and physiological traits of plants, and especially their ...photosynthetic capacity. We investigated the responses of Leymus chinensis to light, medium, and heavy grazing intensities in comparison with a grazing exclusion control.
With light grazing, L. chinensis showed decreased photosynthetic capacity. The low chlorophyll and carotenoid contents constrained light energy transformation and dissipation, and Rubisco activity was also low, restricting the carboxylation efficiency. In addition, the damaged photosynthetic apparatus accumulated reactive oxygen species (ROS). With medium grazing, more energy was used for thermal dissipation, with high carotene content and high non-photochemical quenching, whereas photosynthetic electron transport was lowest. Significantly decreased photosynthesis decreased leaf C contents. Plants decreased the risk caused by ROS through increased energy dissipation. With high grazing intensity, plants changed their strategy to improve survival through photosynthetic compensation. More energy was allocated to photosynthetic electron transport. Though heavy grazing damaged the chloroplast ultrastructure, adjustment of internal mechanisms increased compensatory photosynthesis, and an increased tiller number facilitated regrowth after grazing.
Overall, the plants adopted different strategies by adjusting their metabolism and growth in response to their changing environment.
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