Mechanisms of microenvironmental conditioning in non-Hodgkin’s lymphoma

Tumours are not autonomous transformed cell populations, but rather a society composed of both malignant and normal, including immune, cells that together foster tumour growth and development. Tumour-associated macrophages have been reported to enhance tumour growth, progression and metastasis. In high-grade non-Hodgkin’s lymphomas, prototypically the B-cell neoplasm, Burkitt’s lymphoma (BL), infiltrating macrophages engulf large numbers of apoptotic tumour cells. Evidence suggests that apoptotic BL cells can condition the tumour microenvironment to promote lymphoma development by selectively attracting macrophages while inhibiting neutrophil infiltration and by stimulating macrophages to produce the B-cell growth and survival factor. Tumour cells grow in a hypoxic and nutrient-deficient environment and the resultant cellular stress can induce apoptosis. It is therefore possible that hostile environmental conditions in the tumour also contribute to the generation of a pro-tumour microenvironment. This thesis describes investigations which examined this hypothesis. BL cells were cultured at high density to mimic conditions of metabolic stress existing in the tumour environment. Cell-free supernatants from such stressed BL cells demonstrated potent chemoattractive activity for mononuclear phagocytes. Supernatants from BL cells that were protected from apoptosis by over-expression of bcl-2 had similar ability, confirming that chemoattractant release was apoptosis-independent. The observation that apyrase and suramin could inhibit the chemotactic activity of these supernatants suggested that nucleotides might be the apoptosis-independent chemoattractant. Detection of ATP in stress supernatants by bioluminescence assay was consistent with this proposal. Significantly, supernatants from BL cells and those transfected with bcl-2 were both found to inhibit neutrophil migration, suggesting the occurrence of a neutrophil migration inhibitory factor whose release was apoptosis-independent. Furthermore, stress supernatants could promote BL cell proliferation in vitro, which was apoptosis and cell line-independent. In order to study the role of TAM in the tumour microenvironment, a novel macrophage model was devised using mouse embryonic stem cells (ES cells). Cells derived from ES cells generated in vitro expressed macrophage-specific markers and were free of dendritic cells and undifferentiated ES cells. ES cell-derived macrophages (ESDM) could migrate towards apoptotic BL cells and engulf them. However, ESDM migrated to stress supernatants with decreasing efficiency as they matured. Preliminary data indicated that the phagocytic ability of ESDM to engulf apoptotic cells increased as they matured, consistent with distinct roles for circulating monocytes and tissue macrophages with regard to this function. Considering the high yields and purities of ESDM described here, together with their non-malignant nature and genetic versatility these cells should provide a superior source of undifferentiated mononuclear phagocytes with which to elucidate the molecular mechanisms underlying tumour infiltration and microenvironmental conditioning by TAM. In conclusion, this work suggests that under conditions of pre-apoptotic stress, BL cells have the capacity to regulate their micro-environment upstream of their apoptosis programme to promote net tumour growth through paracrine signals that attract supportive macrophages and inhibit destructive neutrophils and through release of autocrine/juxtacrine tumour growth factors

Terahertz Sources, Detectors, and Transceivers in Silicon Technologies

With active devices lingering on the brink of activity and every passive device and interconnection on chip acting as potential radiator, a paradigm shift from “top-down” to “bottom-up” approach in silicon terahertz (THz) circuit design is clearly evident as we witness orders-of-magnitude improvements of silicon THz circuits in terms of output power, phase noise, and sensitivity since their inception around 2010. That is, the once clear boundary between devices, circuits, and function blocks is getting blurrier as we push the devices toward their limits. And when all else fails to meet the system requirements, which is often the case, a logical step forward is to scale these THz circuits to arrays. This makes a lot of sense in the terahertz region considering the relatively efficient on-chip THz antennas and the reduced size of arrays with half-wavelength pitch. This chapter begins with the derivation of conditions for maximizing power gain of active devices. Discussions of circuit topologies for THz sources, detectors, and transceivers with emphasis on their efficacy and scalability ensue, and this chapter concludes with a brief survey of interface options for channeling THz energy out of the chip

Dew formation characteristics in the gravel desert ecosystem and its ecological roles on Reaumuria soongorica

As an additional source of water to plants besides rainfall, dew may have a positive impact on vegetation in the arid ecosystems. Knowledge regarding dew formation characteristics and its ecological effects on vegetation water status and photosynthetic performance in the gravel desert ecosystem is still lacking. In this study, the dew variability and formation frequency on a gravel desert were measured by microlysimeters. We quantified dew formation characteristics, investigated vegetation water response to dew events in the gravel desert ecosystem at the edge of a desert oasis, Northwestern China. The results showed water adsorption was a primary pathway of dew formation in such system, and the average daily amount of dew is 0.06 mm. Dew occurred on 36% of growing season days, the number of days with dew amounts >0.03 mm accounted for 82% of the total dew events, and the cumulative amount of dew for those days was 3.41 mm. Relative humidity, air temperature, wind speed, the difference between air temperature and soil surface temperature had significant effects on dew formation. A threshold of RH ≥30% is taken to mark possible condensation in the gravel desert ecosystem. A significant positive correlation between dew amounts and the relative moisture in the near-surface air was found when RH ≥30%. The moderate wind velocity (1–1.8 m/s) was favorable to dew formation, and when wind speed >5.47 m/s, there was no dew formation. Because of the water-absorbing scales on the leaves of Reaumuria soongorica, dew events significantly improved their relative water content, water potential, and photosynthetic performance in the early morning and ameliorating the adverse effects of plants exposed to prolonged drought. The study highlights dew is an important supplementary source of water in the gravel desert ecosystem. Although the absolute dew amounts were found not high, it can be a frequent and stable water resource. Furthermore, this study provides a comprehensive understanding of the effects of dew on plant water status in the gravel desert ecosystem

Increased human pressures on the alpine ecosystem along the Qinghai-Tibet Railway

Construction of the Qinghai-Tibet Railway (QTR) increased the links between inland China and the Qinghai-Tibet Plateau (QTP). The QTR accelerated surrounding tourism, boosted the local economy and led to rapid development of livestock raising. To assess how distance from the railway and different regions has influenced the impact of the QTR on the alpine ecosystem, human footprint maps were produced to indicate human pressures, and the normalized difference vegetation index (NDVI), an index of vegetation greenness, was used to characterize the growth of alpine vegetation. The construction and operation of the QTR have increased human pressures, while the establishment of nature reserves has effectively reduced human pressures. The QTR contributes significantly to the increased human pressures in the Tibetan region compared with the Qinghai region and exerts negative impacts on alpine vegetation. Although the warmer and wetter climate trend has proven beneficial in enhancing alpine vegetation greenness, the declining trend of alpine vegetation has been stronger in regions with more intensive human pressures, especially in the grazing areas and the tourist areas around Lhasa. These results suggest that the impact of the QTR on alpine vegetation in Tibet is greater than that in Qinghai and that the spatial extent of the indirect impact of the QTR in Tibet is confined to approximately 30 km from the railway. These results will provide guidance and a theoretical basis for the protection of the alpine environment on the QTP under intensified anthropogenic influence

Genome-wide identification of germin-like proteins in peanut (Arachis hypogea L.) and expression analysis under different abiotic stresses

Peanut is an important food and feed crop, providing oil and protein nutrients. Germins and germin-like proteins (GLPs) are ubiquitously present in plants playing numerous roles in defense, growth and development, and different signaling pathways. However, the GLP members have not been comprehensively studied in peanut at the genome-wide scale. We carried out a genome-wide identification of the GLP genes in peanut genome. GLP members were identified comprehensively, and gene structure, genomic positions, motifs/domains distribution patterns, and phylogenetic history were studied in detail. Promoter Cis-elements, gene duplication, collinearity, miRNAs, protein-protein interactions, and expression were determined. A total of 84 GLPs (AhGLPs ) were found in the genome of cultivated peanut. These GLP genes were clustered into six groups. Segmental duplication events played a key role in the evolution of AhGLPs, and purifying selection pressure was underlying the duplication process. Most AhGLPs possessed a well-maintained gene structure and motif organization within the same group. The promoter regions of AhGLPs contained several key cis-elements responsive to ‘phytohormones’, ‘growth and development’, defense, and ‘light induction’. Seven microRNAs (miRNAs) from six families were found targeting 25 AhGLPs. Gene Ontology (GO) enrichment analysis showed that AhGLPs are highly enriched in nutrient reservoir activity, aleurone grain, external encapsulating structure, multicellular organismal reproductive process, and response to acid chemicals, indicating their important biological roles. AhGLP14, AhGLP38, AhGLP54, and AhGLP76 were expressed in most tissues, while AhGLP26, AhGLP29, and AhGLP62 showed abundant expression in the pericarp. AhGLP7, AhGLP20, and AhGLP21, etc., showed specifically high expression in embryo, while AhGLP12, AhGLP18, AhGLP40, AhGLP78, and AhGLP82 were highly expressed under different hormones, water, and temperature stress. The qRT-PCR results were in accordance with the transcriptome expression data. In short, these findings provided a foundation for future functional investigations on the AhGLPs for peanut breeding programs

Combination of a mitogen‐activated protein kinase inhibitor with the tyrosine kinase inhibitor pacritinib combats cell adhesion‐based residual disease and prevents re‐expansion of FLT3 ‐ITD acute myeloid leukaemia

Minimal residual disease (MRD) in acute myeloid leukaemia (AML) poses a major challenge due to drug insensitivity and high risk of relapse. Intensification of chemotherapy and stem cell transplantation are often pivoted on MRD status. Relapse rates are high even with the integration of first‐generation FMS‐like tyrosine kinase 3 (FLT3) inhibitors in pre‐ and post‐transplant regimes and as maintenance in FLT3 ‐mutated AML. Pre‐clinical progress is hampered by the lack of suitable modelling of residual disease and post‐therapy relapse. In the present study, we investigated the nature of pro‐survival signalling in primary residual tyrosine kinase inhibitor (TKI)‐treated AML cells adherent to stroma and further determined their drug sensitivity in order to inform rational future therapy combinations. Using a primary human leukaemia‐human stroma model to mimic the cell–cell interactions occurring in patients, the ability of several TKIs in clinical use, to abrogate stroma‐driven leukaemic signalling was determined, and a synergistic combination with a mitogen‐activated protein kinase (MEK) inhibitor identified for potential therapeutic application in the MRD setting. The findings reveal a common mechanism of stroma‐mediated resistance that may be independent of mutational status but can be targeted through rational drug design, to eradicate MRD and reduce treatment‐related toxicity

Are the shoreline and eutrophication of desert lakes related to desert development?

Desert lakes are unique ecosystems found in oases within desert landscapes. Despite the numerous studies on oases, there are no reports regarding the spatiotemporal distribution and causes of eutrophication in the desert lakes that are located at the edge of the Linze Oasis in northwestern China. In this study, the seasonal shoreline and eutrophication of a desert lake were monitored using an unmanned aerial vehicle (UAV) and water sampling during three crop growth stages. The spatial extents of the shoreline and algal blooms and the chromophoric dissolved organic matter (CDOM) absorption coefficient were derived through UAV images. The desert lake shoreline declined during the crop growing stage, which exhibited the largest water demand and began to expand after this stage. The estimated CDOM absorption coefficient measurements and classified algal bloom area showed seasonal variations that increased from spring to late summer and then decreased in autumn. The first two crop growth stages accounted for most of the water and fertilizer requirements of the entire growth period, which may have contributed to large amounts of groundwater consumption and pollution and resulted in peak eutrophication of the lake in the second growth stage. However, the CDOM absorption coefficient of the third stage was not well correlated with that of the first two stages, suggesting that the lake may be affected by the dual effects of groundwater and precipitation recharge in the third stage. These results indicate that the water quality of desert lakes may be affected by agricultural cultivation. The agricultural demands for water and fertilizer may change the spatiotemporal changes in water quality in the lake, especially in the middle and early stages of crop growth

Mechanisms of microenvironmental conditioning in non-Hodgkin's lymphoma

Tumours are not autonomous transformed cell populations, but rather a society composed of both malignant and normal, including immune, cells that together foster tumour growth and development. Tumour-associated macrophages have been reported to enhance tumour growth, progression and metastasis. In high-grade non-Hodgkin’s lymphomas, prototypically the B-cell neoplasm, Burkitt’s lymphoma (BL), infiltrating macrophages engulf large numbers of apoptotic tumour cells. Evidence suggests that apoptotic BL cells can condition the tumour microenvironment to promote lymphoma development by selectively attracting macrophages while inhibiting neutrophil infiltration and by stimulating macrophages to produce the B-cell growth and survival factor. Tumour cells grow in a hypoxic and nutrient-deficient environment and the resultant cellular stress can induce apoptosis. It is therefore possible that hostile environmental conditions in the tumour also contribute to the generation of a pro-tumour microenvironment. This thesis describes investigations which examined this hypothesis. BL cells were cultured at high density to mimic conditions of metabolic stress existing in the tumour environment. Cell-free supernatants from such stressed BL cells demonstrated potent chemoattractive activity for mononuclear phagocytes. Supernatants from BL cells that were protected from apoptosis by over-expression of bcl-2 had similar ability, confirming that chemoattractant release was apoptosis-independent. The observation that apyrase and suramin could inhibit the chemotactic activity of these supernatants suggested that nucleotides might be the apoptosis-independent chemoattractant. Detection of ATP in stress supernatants by bioluminescence assay was consistent with this proposal. Significantly, supernatants from BL cells and those transfected with bcl-2 were both found to inhibit neutrophil migration, suggesting the occurrence of a neutrophil migration inhibitory factor whose release was apoptosis-independent. Furthermore, stress supernatants could promote BL cell proliferation in vitro, which was apoptosis and cell line-independent. In order to study the role of TAM in the tumour microenvironment, a novel macrophage model was devised using mouse embryonic stem cells (ES cells). Cells derived from ES cells generated in vitro expressed macrophage-specific markers and were free of dendritic cells and undifferentiated ES cells. ES cell-derived macrophages (ESDM) could migrate towards apoptotic BL cells and engulf them. However, ESDM migrated to stress supernatants with decreasing efficiency as they matured. Preliminary data indicated that the phagocytic ability of ESDM to engulf apoptotic cells increased as they matured, consistent with distinct roles for circulating monocytes and tissue macrophages with regard to this function. Considering the high yields and purities of ESDM described here, together with their non-malignant nature and genetic versatility these cells should provide a superior source of undifferentiated mononuclear phagocytes with which to elucidate the molecular mechanisms underlying tumour infiltration and microenvironmental conditioning by TAM. In conclusion, this work suggests that under conditions of pre-apoptotic stress, BL cells have the capacity to regulate their micro-environment upstream of their apoptosis programme to promote net tumour growth through paracrine signals that attract supportive macrophages and inhibit destructive neutrophils and through release of autocrine/juxtacrine tumour growth factors.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Mechanisms of microenvironmental conditioning in non-Hodgkin's lymphoma

Tumours are not autonomous transformed cell populations, but rather a society composed of both malignant and normal, including immune, cells that together foster tumour growth and development. Tumour-associated macrophages have been reported to enhance tumour growth, progression and metastasis. In high-grade non-Hodgkin’s lymphomas, prototypically the B-cell neoplasm, Burkitt’s lymphoma (BL), infiltrating macrophages engulf large numbers of apoptotic tumour cells. Evidence suggests that apoptotic BL cells can condition the tumour microenvironment to promote lymphoma development by selectively attracting macrophages while inhibiting neutrophil infiltration and by stimulating macrophages to produce the B-cell growth and survival factor. Tumour cells grow in a hypoxic and nutrient-deficient environment and the resultant cellular stress can induce apoptosis. It is therefore possible that hostile environmental conditions in the tumour also contribute to the generation of a pro-tumour microenvironment. This thesis describes investigations which examined this hypothesis. BL cells were cultured at high density to mimic conditions of metabolic stress existing in the tumour environment. Cell-free supernatants from such stressed BL cells demonstrated potent chemoattractive activity for mononuclear phagocytes. Supernatants from BL cells that were protected from apoptosis by over-expression of bcl-2 had similar ability, confirming that chemoattractant release was apoptosis-independent. The observation that apyrase and suramin could inhibit the chemotactic activity of these supernatants suggested that nucleotides might be the apoptosis-independent chemoattractant. Detection of ATP in stress supernatants by bioluminescence assay was consistent with this proposal. Significantly, supernatants from BL cells and those transfected with bcl-2 were both found to inhibit neutrophil migration, suggesting the occurrence of a neutrophil migration inhibitory factor whose release was apoptosis-independent. Furthermore, stress supernatants could promote BL cell proliferation in vitro, which was apoptosis and cell line-independent. In order to study the role of TAM in the tumour microenvironment, a novel macrophage model was devised using mouse embryonic stem cells (ES cells). Cells derived from ES cells generated in vitro expressed macrophage-specific markers and were free of dendritic cells and undifferentiated ES cells. ES cell-derived macrophages (ESDM) could migrate towards apoptotic BL cells and engulf them. However, ESDM migrated to stress supernatants with decreasing efficiency as they matured. Preliminary data indicated that the phagocytic ability of ESDM to engulf apoptotic cells increased as they matured, consistent with distinct roles for circulating monocytes and tissue macrophages with regard to this function. Considering the high yields and purities of ESDM described here, together with their non-malignant nature and genetic versatility these cells should provide a superior source of undifferentiated mononuclear phagocytes with which to elucidate the molecular mechanisms underlying tumour infiltration and microenvironmental conditioning by TAM. In conclusion, this work suggests that under conditions of pre-apoptotic stress, BL cells have the capacity to regulate their micro-environment upstream of their apoptosis programme to promote net tumour growth through paracrine signals that attract supportive macrophages and inhibit destructive neutrophils and through release of autocrine/juxtacrine tumour growth factors.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The hidden costs of desert development

Economic benefits and ecological restoration are the leading drivers of desert development through man-made oasis expansion. However, the sustainability of oasis expansion in combating desertification while promoting economic growth remains unclear, though such knowledge is critical for future desert development across the globe. To address this knowledge gap, a comprehensive assessment integrating meteorological, groundwater and remote-sensing data as well as groundwater simulation datasets was conducted to evaluate the spatial-temporal changes in the desert-oasis ecotone of northwest China over the past six decades. Desert development causes a rapid decline in the surrounding groundwater table, increases pollution in soil and groundwater and is associated with an increased frequency of strong sandstorms. Desert development seems to have improved the environment and promoted the economy, but there is a huge cost for the overexploitation of water resources and the transfer of pollution from surface to underground, which could cause deserts to degrade further