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Accurate estimation for vegetation net primary production (NPP) at high resolution is essential for ecosystem management and at local to global scales. However, no reliable methods are available to achieve fine-resolution estimation. In this study, a new NPP estimation system was developed by integrating high spatial resolution remote sensing images, tree ring measurements, and process-based model CASA. The system was illustrated by estimating the historical NPP of caragana shrublands from 2011 to 2021 in Dingbian County, China. The results showed that: (1) by employing the biomass model and tree ring measurements, an NPP-crown width model was established to enable a large number of samples for calibrating the CASA model on high spatial resolution images without continuous field measurements. The calibrated parameters, including maximum NDVI, minimum NDVI, and maximum light use efficiency, were determined to be 0.415, 0.022 and 0.025, respectively; (2) according to the estimation by the calibrated CASA model, the NPP in Dingbian County revealed an increasing trend from 2011 to 2021, and the NPP in southern hilly and gully regions was significantly higher than the other regions; (3) among the different indices, max temperature of warmest month had a significant negative effect on the NPP of cagarana shrublands, whereas annual precipitation had a positive effect. In the northern and central regions, air temperature predominantly influenced NPP, while in the southern regions, both temperature and precipitation played a joint role. The implementation in this study illustrated that the NPP estimation system could provide reliable NPP with high resolution and efficient to monitor and detect dominant factors affecting NPP for ecosystem management. [ABSTRACT FROM AUTHOR]

Biofuel is encouraged because of its low impact on climate change. A new framework was developed to accurately assess the climate change impacts (CCI) of biofuel by integrating the atmospheric carbon cycle model and vegetation carbon dynamic models. Forests with different growth rates (fast, medium, slow) and three collection intensities (71%, 52%, 32%) of logging residues were presumed to test the performance of this framework. The CCI of biofuel was analyzed under two functional units: 1 GJ of biofuels and 1 ha of forests to supply biofuels. According to this study, increasing the forest growth rate could decrease the CCI in both functional units. Increasing the collection intensity could decrease the CCI of 1 GJ of biofuel but increase the CCI of 1 ha of forest land (unless the impacts were negative in fast-growth forests with high and medium collection intensities). Producing bioethanol resulted in a lower CCI (−3.1–67.7 kg CO2 eq/GJ) compared to bio-diesel (29.3–94.7 kg CO2 eq/GJ). Hence, collecting all available logging residues (without inhibiting forest regrowth) to produce low CCI biofuels such as bioethanol was found to be the optimal option for achieving high mitigation effects. [ABSTRACT FROM AUTHOR]

The conflict between the mainline and incoming traffic flow in the merging area of an urban expressway makes it easier to form a traffic bottleneck than the basic road section. When the merging bottleneck occurs, the overall efficiency is affected. This paper establishes an improved Cell Transmission Model (CTM) using Genetic Algorithms (GA) and Mean Absolute Percentage Error (MAPE) for parameter calibration and validation. Based on the joint optimization goal of efficiency and safety, a collaborative control strategy is established. The strategy is verified by VISSIM. The results show that the total travel time is reduced by 7.34%, and the total turnover is increased by 6.06% by applying the collaborative control strategy during the peak period. Therefore, the cooperative control strategy of the merging bottleneck proposed can improve the traffic state at the merging bottleneck and improve the efficiency and safety level of the expressway. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer. Studying the pathogenesis of RCC is particularly important, because it could provide a direct guide for clinical treatment. Given that tumor heterogeneity is probably reflected at the mRNA level, the study of mRNA in RCC may reveal some potential tumor-specific markers, especially single-cell RNA sequencing (scRNA-seq). Methods: We performed an exploratory study on three pathological types of RCC with a small sample size. This study presented clear-cell RCC (ccRCC), type 2 pRCC, and chRCC in a total of 30,263 high-quality single-cell transcriptome information from three pathological types of RCC. In addition, scRNA-seq was performed on normal kidneys. Tumor characteristics were well identified by the comparison between different pathological types of RCC and normal kidneys at the scRNA level. Results: Some new tumor-specific markers for different pathologic types of RCC, such as SPOCK1, PTGIS, REG1A, CP and SPAG4 were identified and validated. We also discovered that NDUFA4L2 both highly expressed in tumor cells of ccRCC and type 2 pRCC. The presence of two different types of endothelial cells in ccRCC and type 2 pRCC was also identified and verified. An endothelial cell in ccRCC may be associated with fibroblasts and significantly expressed fibroblast markers, such as POSTN and COL3A1. At last, by applying scRNA-seq results, the activation of drug target pathways and sensitivity to drug responses was predicted in different pathological types of RCC. Conclusions: Taken together, these findings considerably enriched the single-cell transcriptomic information for RCC, thereby providing new insights into the diagnosis and treatment of RCC. [ABSTRACT FROM AUTHOR]

Bilateral renal cell carcinoma (RCC) is a rare disease that can be classified as either familial or sporadic. Studying the cellular molecular characteristics of sporadic bilateral RCC is important to provide guidance for clinical treatment. Cellular molecular characteristics can be expressed at the RNA level, especially at the single-cell degree. Single-cell RNA sequencing (scRNA-seq) was performed on bilateral clear cell RCC (ccRCC). A total of 3,575 and 3,568 high-quality single-cell transcriptome data were captured from the left and right tumour tissues, respectively. Gene characteristics were identified by comparing left and right tumours at the scRNA level. The complex cellular environment of bilateral ccRCC was presented by using scRNA-seq. Single-cell transcriptomic analysis revealed high similarity in gene expression among most of the cell types of bilateral RCCs but significant differences in gene expression among different site tumour cells. Additionally, the potential biological function of different tumour cell types was determined by gene ontology (GO) analysis. The transcriptome characteristics of tumour tissues in different locations at the single-cell transcriptome level were revealed through the scRNA-seq of bilateral sporadic ccRCC. This work provides new insights into the diagnosis and treatment of bilateral RCC. [ABSTRACT FROM AUTHOR]

Mastermind proteins are required for transcription of Notch target genes, yet the molecular basis for mastermind function remains incompletely understood. Previous work has shown that Notch can induce transcriptional responses by binding to promoters, but more often by binding to enhancers, with HES4 and DTX1 as representative mammalian examples of promoter and enhancer responsiveness, respectively. Here, we show that mastermind dependence of the Notch response at these loci is differentially encoded in Jurkat T-cell acute lymphoblastic leukemia (T-ALL) cells. Knockout of Mastermind-like1 (MAML1) eliminates Notch responsive activation of both these genes, and reduced target gene expression is accompanied by a decrease in H3K27 acetylation, consistent with the importance of MAML1 for p300 activity. Add-back of MAML1 variants in knockout cells identifies residues 151-350 of MAML1 as essential for expression of either Notch-responsive gene. Fusion of the Notch-binding region of MAML1 to the histone acetyltransferase (HAT) domain of p300 rescues expression of HES4 but not DTX1, suggesting that an additional activity of MAML1 is needed for gene induction at a distance. Together, these studies establish the functional importance of the MAML1 151-350 region for Notch-dependent transcriptional induction, and reveal differential requirements for MAML1- dependent recruitment activities at different Notch responsive loci, highlighting the molecular complexity of Notch-stimulated transcription. [ABSTRACT FROM AUTHOR]

• One-pot synthesis of surface polyvinyl pyrrolidone modified polypyrrole. • The relationship between polypyrrole structure and physicochemical property. • Polypyrrole exhibits combined tumor photothermal-chemotherapy ability. With an excellent near-infrared (NIR) light-responsive property, polypyrrole (PPy) nanoparticle has emerged as a promising NIR photothermal transducing agent for tumor photothermal therapy (PTT). Herein, we reported the PVP mediated one-pot synthesis of colloidal stable and biocompatible PPy nanoparticles (PPy-PVP NPs) for combined tumor photothermal-chemotherapy. The influence of molecular weight and PVP concentration on the spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency of the resultant PPy-PVP NPs was systematically studied. By choosing PVP with a molecular weight of 360 kDa (concentration of 5 mg/mL) as the template and surface modifier during the synthesis, PPy-PVP NPs with optimal spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency were synthesized. Findings in this study are anticipated to provide an in-depth understanding of the important character of surface engineering in the rational design and biomedical applications of PPy NPs. [ABSTRACT FROM AUTHOR]

Summary Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC , which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex. Expression of direct Notch target genes is associated with Notch activity in an MCL xenograft model and in CLL lymph node biopsies. Our findings provide key insights into the role of Notch in MCL and other B cell malignancies and have important implications for therapeutic targeting of Notch-dependent oncogenic pathways. [ABSTRACT FROM AUTHOR]

The Notch signaling pathway has a critical role in cell fate determination and tissue homeostasis in a variety of different lineages. In the context of normal Notch signaling, the Notch receptor of the ‘signal-receiving’ cell is activated in trans by a Notch ligand from a neighboring ‘signal-sending’ cell. Genetic studies in several model organisms have established that ubiquitination of the Notch ligand, and its regulated endocytosis, is essential for transmission of this activation signal. In mammals, this ubiquitination step is dependent on the protein Mind bomb 1 (Mib1), a large multi-domain RING-type E3 ligase, and its direct interaction with the intracellular tails of Notch ligand molecules. Here, we discuss our current understanding of Mind bomb structure and mechanism in the context of Notch signaling and beyond. [ABSTRACT FROM AUTHOR]

Overexpression of the cellular FLICE-like inhibitory protein (cFLIP) has been reported in a number of tumor types. As an inactive procaspase-8 homologue, cFLIP is recruited to the intracellular assembly known as the Death Inducing Signaling Complex (DISC) where it inhibits apoptosis, leading to cancer cell proliferation. Here we characterize the molecular details of the interaction between cFLIPL and calmodulin, a ubiquitous calcium sensing protein. By expressing the individual domains of cFLIPL, we demonstrate that the interaction with calmodulin is mediated by the N-terminal death effector domain (DED1) of cFLIPL. Additionally, we mapped the interaction to a specific region of the C-terminus of DED1, referred to as DED1 R4. By designing DED1/DED2 chimeric constructs in which the homologous R4 regions of the two domains were swapped, calmodulin binding properties were transferred to DED2 and removed from DED1. Furthermore, we show that the isolated DED1 R4 peptide binds to calmodulin and solve the structure of the peptide-protein complex using NMR and computational refinement. Finally, we demonstrate an interaction between cFLIPL and calmodulin in cancer cell lysates. In summary, our data implicate calmodulin as a potential player in DISC-mediated apoptosis and provide evidence for a specific interaction with the DED1 of cFLIPL. [ABSTRACT FROM AUTHOR]

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, but not alone. The molecule was identified through an in silico chemical screen for compounds with affinity for the caspase 8 homodimer’s interface. The compound was experimentally validated to directly bind caspase 8, and to promote caspase 8 activation and cell death in single living cells or population of cells, upon TRAIL stimulation. Our approach is a proof-of-concept strategy leading to the discovery of a novel small molecule that not only stimulates TRAIL-induced apoptosis in cancer cells, but may also provide insights into the structure-function relationship of caspase 8 homodimers as putative targets in cancer.

We present a versatile method to characterize ATPase and kinase activities and discover new inhibitors of these proteins. The proton NMR-based assay directly monitors ATP turnover and is easy to implement, requires no additional reagents and can potentially be applied to GTP. We validated the method's accuracy, applied it to the monitoring of ATP turnover by actin and to the screening of ATPase inhibitors, and showed that it is also applicable for the monitoring of GTP hydrolysis. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1 , NEUROD1 , POU2F3 , or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes. In neuroendocrine cells, MYC activates Notch to dedifferentiate tumor cells, promoting a temporal shift in SCLC from ASCL1+ to NEUROD1+ to YAP1+ states. MYC alternatively promotes POU2F3+ tumors from a distinct cell type. Human SCLC exhibits intratumoral subtype heterogeneity, suggesting that this dynamic evolution occurs in patient tumors. These findings suggest that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype. • Multiple SCLC molecular subtypes arise from a neuroendocrine cell of origin • MYC drives the NEUROD1+ and YAP1+ subtypes of SCLC in a temporal evolution • MYC directly activates NOTCH signaling to reprogram neuroendocrine fate • Multiple SCLC molecular subtypes are present within individual human tumors Ireland et al. show that MYC activates Notch signaling to dedifferentiate neuroendocrine small cell lung cancer (SCLC) in a conserved trajectory from ASCL1+ to NEUROD1+ to YAP1+ non-neuroendocrine subtypes, suggesting that these are not distinct subtypes but different stages of progressive evolution of SCLC. [ABSTRACT FROM AUTHOR]