Pedology of archaeological soils in tells of the Judean foothills, Israel

Tells (archaeological mounds) predominantly consist of poorly consolidated to unconsolidated sediments, and soils that are highly anthropogenic. This study examines pedogenic processes related to carbonate mobilization in tells in comparison with their peripheral soils (reference soil profiles). The key objective of this study is to test the hypothesis that tell deposits evolve through concurrent processes of sedimentation and pedogenesis (synlithogenic pedogenesis), and further explain it. Case studies are presented from three tells in semi-arid and Mediterranean climatic zones of the Levant. The methods applied included field survey, analyses of particle size distribution, pH, %CaCO and organic carbon content, and soil micromorphology. Soils of the tells contain miscellaneous cultural materials that derive mainly from degraded mud bricks, pottery and burnt wood. Chemical data show basic pH values, high CaCO content, and minor amounts of organic carbon. Field observations and lab analyses both indicate high similarity amongst the tells and their reference soil profiles. Buried tell soils show same characteristics as near-surface soils. However, the reference soil profiles show incipient horizonation, slightly darker colours, and more developed structure. Micromorphology of both the tells and the reference profiles show cohesively welded peds in a vughy microstructure, groundmass with an open porphyric c/f-related distribution, and discontinuous carbonate recrystallization. Relative rates of soil formation in the tells can be estimated when archaeological records are established. Contrary to the tells, the reference soil profiles show lower porosity and only minor remnants related to earth construction materials. We classify the soils of the studied tells as archaeological Calcareous Anthraltic Xerorthents. The correlative WRB classification would be Calcic Urbic Technosols (Archaic). The anthropogenic materials are as calcareous as the natural soils, but due to human action, carbonates in the tells are distributed differently. Based on these observations, ancient human actions and the dry climate have led to very little mobilization and accumulation of carbonates. The information provided in this study adds to the pedological understanding of archaeological environments. Specifically, it can be useful for the study of site formation processes of tells

Nari in the Levant: historical and etymological aspects of a specific calcrete formation

The colloquial Arabic term nari has become, since the late 1890s, the most commonly used term for describing a specific type of calcrete formation in the Levant. While it is reasonable to expect that such a long period of time would be sufficient for the establishment of a coherent use of the term, a combination of extensive literature reviews with field observations prove otherwise. A study of the geological contexts and etymology of the term nari and a review of literature back as far as the second half of the nineteenth century reveal a great lack of consistency among scientists' use of the term. Correlating the terminological evolution of nari with present-day understanding of its formation mechanisms, its stratigraphic associations and contemporary uses of the term among scientists and local Arabs, allows us to propose a clear and consistent definition of nari. Our suggested definition recognizes it as a distinct surficial lithology. We show that the formation of nari in the Levant started in a regional calcretisation event in the late Pliocene to mid Pleistocene and is ongoing in the Levant nowadays

High-throughput and targeted drug screens identify pharmacological candidates against MiT-translocation renal cell carcinoma

Abstract Background MiT-Renal Cell Carcinoma (RCC) is characterized by genomic translocations involving microphthalmia-associated transcription factor (MiT) family members TFE3, TFEB, or MITF. MiT-RCC represents a specific subtype of sporadic RCC that is predominantly seen in young patients and can present with heterogeneous histological features making diagnosis challenging. Moreover, the disease biology of this aggressive cancer is poorly understood and there is no accepted standard of care therapy for patients with advanced disease. Tumor-derived cell lines have been established from human TFE3-RCC providing useful models for preclinical studies. Methods TFE3-RCC tumor derived cell lines and their tissues of origin were characterized by IHC and gene expression analyses. An unbiased high-throughput drug screen was performed to identify novel therapeutic agents for treatment of MiT-RCC. Potential therapeutic candidates were validated in in vitro and in vivo preclinical studies. Mechanistic assays were conducted to confirm the on-target effects of drugs. Results The results of a high-throughput small molecule drug screen utilizing three TFE3-RCC tumor-derived cell lines identified five classes of agents with potential pharmacological efficacy, including inhibitors of phosphoinositide-3-kinase (PI3K) and mechanistic target of rapamycin (mTOR), and several additional agents, including the transcription inhibitor Mithramycin A. Upregulation of the cell surface marker GPNMB, a specific MiT transcriptional target, was confirmed in TFE3-RCC and evaluated as a therapeutic target using the GPNMB-targeted antibody-drug conjugate CDX-011. In vitro and in vivo preclinical studies demonstrated efficacy of the PI3K/mTOR inhibitor NVP-BGT226, Mithramycin A, and CDX-011 as potential therapeutic options for treating advanced MiT-RCC as single agents or in combination. Conclusions The results of the high-throughput drug screen and validation studies in TFE3-RCC tumor-derived cell lines have provided in vitro and in vivo preclinical data supporting the efficacy of the PI3K/mTOR inhibitor NVP-BGT226, the transcription inhibitor Mithramycin A, and GPNMB-targeted antibody-drug conjugate CDX-011 as potential therapeutic options for treating advanced MiT-RCC. The findings presented here should provide the basis for designing future clinical trials for patients with MiT-driven RCC