Th/K and Th/U ratios from spectral gamma-ray surveys improve the mapped definition of subsurface structures

Spectral gamma-ray data can be obtained by non-destructive, automated, rapid and inexpensive survey methods. Previous studies utilise only total count, or total count as well as K, U and Th data. This work examines the use of Th/K and Th/U ratios to define the subsurface extent of partially-buried features at the centimeter to meter scale. On-site results are presented from two case studies as two-dimensional cross-sections. Changes in Th/K and Th/U ratios coincide with the known location of buried structures to within 10cm horizontal resolution. Gradual changes in total count, K, U and Th measurements give a lower horizontal accuracy of 30cmto1m. Grids of data were manipulated in ArcGIS™ using a thin plate spline function to maximise information use and provide ‘easy to interpret’ maps of the survey areas. Unlike total count or individual element maps, Th/K and Th/U ratio maps can be compared to the known location of subsurface structures, vindicating the use of ratio cross-sections and maps in archaeological, geotechnical and forensic applications. It is concluded that the capacity to observe sub-surface features is enhanced through the use of Th/K and Th/U ratios

Amazonian Ayahuasca and Mental Health Outcomes

Ayahuasca is a psychedelic plant brew originating from the Amazon Rainforest. It is formed from two basic components, the Banisteriopsis caapi vine, and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. There has been a dramatic increase in interest surrounding ayahuasca since the turn of the millennium. Increasing numbers of tourists are travelling to the Amazon rainforest to drink the brew, with various media outlets, celebrities, and researchers describing benefit from its consumption. Ayahuasca is now present in every continent and retreat centres offering plant medicine experiences in the Amazon rainforest has become a thriving business. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. This thesis comprises five studies investigating Amazonian ayahuasca use. Initially, the pharmacology of the brew is explored in the form of a systematic review, concluding complex synergistic mechanisms may be present, although further research is needed. The remaining studies utilise observational methodology, investigating the impact of ayahuasca retreats following a traditional Shipibo lineage adapted for ayahuasca tourists in the Peruvian Amazon. The effects of the brew on personality, mental health outcomes, epigenetics, and nature relatedness are documented. Further, a phenomenological analysis of the ayahuasca experience is included. The research in this thesis is amongst the first to investigate Shipibo-style ayahuasca retreats in the Peruvian Amazon. Various ethical issues surrounding the increasing popularity of the brew and potential medicalisation are also discussed. It is hoped that this research will add to the growing body of knowledge surrounding the potential therapeutic effects of ayahuasca, whilst considering risks, ethics, and wider applications

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

Cell Cycle- and Cancer-Associated Gene Networks Activated by Dsg2: Evidence of Cystatin A Deregulation and a Potential Role in Cell-Cell Adhesion

This work was supported by grants from the National Institutes of Health (Mahoney, R01AR056067; Riobo, RO1 GM088256). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Intricate macrophage-colorectal cancer cell communication in response to radiation

Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively. Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar fractionated scheme to that used during cancer patients' treatment (2 Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co-culture with macrophages increased the mRNA expression of metabolism- and survival-related genes more in SW1463 than in RKO. The presence of macrophages also upregulated glucose transporter 1 expression in irradiated SW1463, but not in RKO cells. In addition, the influence of cancer cells on the expression of pro- and anti-inflammatory macrophage markers, upon radiation exposure, was also evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti-inflammatory CCL18. However, RKO cells induce an increase of macrophage pro-inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data demonstrated that macrophages and cancer cells mutually influence their response to radiation. Notably, conditioned medium from irradiated co-cultures increased non-irradiated RKO cell migration and invasion and did not impact on angiogenesis in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of primary human macrophage-cancer cell co-cultures revealed an intricate cell communication in response to ionizing radiation, which should be considered when developing therapies adjuvant to radiotherapy

Rapid glacial retreat on the Kamchatka Peninsula during the early 21st century

© Author(s) 2016. Monitoring glacier fluctuations provides insights into changing glacial environments and recent climate change. The availability of satellite imagery offers the opportunity to view these changes for remote and inaccessible regions. Gaining an understanding of the ongoing changes in such regions is vital if a complete picture of glacial fluctuations globally is to be established. Here, satellite imagery (Landsat 7, 8 and ASTER) is used to conduct a multi-annual remote sensing survey of glacier fluctuations on the Kamchatka Peninsula (eastern Russia) over the 2000-2014 period. Glacier margins were digitised manually and reveal that, in 2000, the peninsula was occupied by 673 glaciers, with a total glacier surface area of 775.7ĝ€±ĝ€27.9ĝ€km2. By 2014, the number of glaciers had increased to 738 (reflecting the fragmentation of larger glaciers), but their surface area had decreased to 592.9ĝ€±ĝ€20.4ĝ€km2. This represents a ĝ1/4 ĝ€24ĝ€% decline in total glacier surface area between 2000 and 2014 and a notable acceleration in the rate of area loss since the late 20th century. Analysis of possible controls indicates that these glacier fluctuations were likely governed by variations in climate (particularly rising summer temperatures), though the response of individual glaciers was modulated by other (non-climatic) factors, principally glacier size, local shading and debris cover

Cyclic AMP Responsive Element Binding Proteins Are Involved in ‘Emergency’ Granulopoiesis through the Upregulation of CCAAT/Enhancer Binding Protein β

In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBPβ. In this study, a novel lentivirus-based reporter system was developed to elucidate the molecular switch required for C/EBPβ-dependency. The results demonstrated that two cyclic AMP responsive elements (CREs) in the proximal promoter region of C/EBPβ were involved in the positive regulation of C/EBPβ transcription during granulocyte-macrophage colony-stimulating factor (GM-CSF)–induced differentiation of bone marrow cells. In addition, the transcripts of CRE binding (CREB) family proteins were readily detected in hematopoietic stem/progenitor cells. CREB was upregulated, phosphorylated and bound to the CREs in response to GM-CSF stimulation. Retroviral transduction of a dominant negative CREB mutant reduced C/EBPβ mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBPβ transcription. These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBPβ upregulation