Geoarchaeology and Heritage Management:Identifying and Quantifying Multi-Scalar Erosional Processes at Kisese II Rockshelter, Tanzania

Natural and anthropogenically induced soil erosion can cause serious loss of the archaeological record. Our work shows the value of multi-scalar geoarchaeological study when excavating and re-excavating rockshelters in a highly dynamic sedimentary environment where erosion is prominent. Here we present our work on Kisese II rockshelter, Tanzania, originally excavated in the 1950s and largely unpublished, that preserves an important Pleistocene-Holocene archaeological record integral to understanding the deep history of the Kondoa Rock-Art World Heritage Center. Unlike rockshelters in quiescent tectonic settings, like much of central Europe or South Africa, Kisese II exists in highly dynamic sedimentary environments associated with the active tectonics of the Great Rift Valley system exacerbated by human-induced environmental and climate change. We report on our 2017 and 2019 exploratory research that includes integrated regional-, landscape-, and site-scale geoarchaeological analyses of past and present sedimentary regimes and micromorphological analyses of the archaeological sediments. Historical records and aerial photographs document extensive changes in vegetation cover and erosional regimes since the 1920s, with drastic changes quantified between 1960 and 2019. Field survey points to an increased erosion rate between 2017 and 2019. To serve future archaeologists, heritage specialists, and local populations we combine our data in a geoarchaeological catena that includes soil, vegetation, fauna, and anthropogenic features on the landscape. At the site, micromorphological coupled with chronological analyses demonstrate the preservation of in situ Pleistocene deposits. Comparison of photographs from the 1956 and 2019 excavations show a maximum sediment loss of 68 cm in 63 years or >10% of >6-m-thick sedimentary deposit. In the studied area of the rockshelter we estimate ∼1 cm/yr of erosion, suggesting the ongoing removal of much of the higher archaeological sediments which, based on the coarse stratigraphic controls and chronology of the original Inskeep excavations, would suggest the loss of much of the archaeological record of the last ∼4000 years. These multi-scalar data are essential for the construction of appropriate mitigation strategies and further study of the remaining stratigraph

An In Vivo CRISPR Screening Platform for Prioritizing Therapeutic Targets in AML

CRISPR-Cas9-based genetic screens have successfully identified cell type-dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival. Because most of these screens have been performed in vitro using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies in vivo, including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing. Our integrated pipeline has revealed several targets with translational value, including SLC5A3 as a metabolic vulnerability for AML addicted to exogenous myo-inositol and MARCH5 as a critical guardian to prevent apoptosis in AML. MARCH5 repression enhanced the efficacy of BCL2 inhibitors such as venetoclax, further highlighting the clinical potential of targeting MARCH5 in AML. Our study provides a valuable strategy for discovery and prioritization of new candidate AML therapeutic targets. SIGNIFICANCE: There is an unmet need to improve the clinical outcome of AML. We developed an integrated in vivo screening approach to prioritize and validate AML dependencies with high translational potential. We identified SLC5A3 as a metabolic vulnerability and MARCH5 as a critical apoptosis regulator in AML, both of which represent novel therapeutic opportunities.This article is highlighted in the In This Issue feature, p. 275

Availability, Awareness, Attitude and Knowledge of Emergency Contraceptives in Dar Es Salaam

Contraceptive methods are useful in family planning and prevention of unwanted pregnancies. Studies done in different countries however have reported poor knowledge and low use of these contraceptives especially the emergency contraceptive pills (ECP). In Tanzania, the awareness and knowledge of women about ECP is not well documented. The aim of this study was to assess awareness, knowledge and attitude of female university students on ECP and the availability of these pills in selected medicines outlets located in Dar Es Salaam city. A descriptive cross sectional study was carried out using a self administered questionnaire to assess knowledge and attitude towards emergency contraceptive pills among female university students. The simulated client method was used to assess availability of the pills in pharmacies and part II shops in the city. A total of 350 female students participated in this study of whom, 57 % were aware of ECP and only 14 % had used them. About half (49%) of the participants had poor knowledge on ECP. The study revealed that 42.3 % of the pharmacies and 30 % of Part II shops surveyed stock only one brand of ECP which was not registered by the regulatory Authority. To conclude, low awareness and poor knowledge on ECP was observed among the study population. Only one brand of emergency contraceptive pills was available in both Pharmacies and Part II shops. Unfortunately this brand was not registered by the regulatory authority. Key words: attitude, awareness, emergency contraceptives, knowledge, unwanted pregnancy

Kisese II Rockshelter, Tanzania

Located in the UNESCO World Heritage Center in Kondoa, Tanzania, the Kisese II rock shelter (4.49° S, 35.81° E,) preserves an extensive record of intermittent human use over at least the last 45,000 years, maintaining a varying role over time as a habitation site, a place for burial, and a canvas for making rock art. An archaeological investigation of the site was initiated in 1951 by Louis and Mary Leakey but was never published. During this time, the Leakeys were conducting extensive field research in Kondoa in search of archaeological evidence that could be used to refine the age of the rock paintings in the area. At Kisese II they placed a c. 4 × 2 m trench and reached over 4 m depth. The abundance of finds and the unusual depth of the archaeological deposit at Kisese II compared to the other nearby tested locations prompted the Leakeys to enlist the help of Ray Inskeep to continue investigating the site. The site provides evidence for changes in how stone tools, ostrich eggshell beads, and ochre technologies were made and used, and the archaeological deposit appears to sample the Last Glacial Maximum, an interval of climate dynamism not well-preserved in many other eastern African localities

An in vivo CRISPR screening platform for prioritizing therapeutic targets in AML

CRISPR–Cas9-based genetic screens have successfully identified cell type–dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival. Because most of these screens have been performed in vitro using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies in vivo, including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing. Our integrated pipeline has revealed several targets with translational value, including SLC5A3 as a metabolic vulnerability for AML addicted to exogenous myo-inositol and MARCH5 as a critical guardian to prevent apoptosis in AML. MARCH5 repression enhanced the efficacy of BCL2 inhibitors such as venetoclax, further highlighting the clinical potential of targeting MARCH5 in AML. Our study provides a valuable strategy for discovery and prioritization of new candidate AML therapeutic targets