Research Reports from the Programme for Belize Archaeological Project, Volume Six

Table of Contents : Background and Introduction to the 2011 Season of the Programme for Belize Archaeological Project / by Fred Valdez, Jr. and Marisol Cortes-Rincon (p.1-4) -- Investigations at Structure 3, La Milpa: The 2011 Field Season / by Debora Trein (p.5-32) -- Report of the 2011 Excavations at the South Ballcourt of La Milpa, Op A6 / by David Chatelain (p.33-44) -- Summary of the 2011 Activities of the La Milpa Core Project / by Brett A. Houk and Gregory Zaro (p.45-54) -- Summary of 2011 Field Season: Examination of Extended Lineages Associated with Courtyards 135 & 149 at La Milpa, Belize / by Brandon S. Lewis (p.55-58) -- Report on a Northern Residential Complex at La Milpa, Belize: Operation LM4 / by Deanna M. Riddick (p.59-62) -- Preliminary Notes on a Chultun Burial at La Milpa – LM-4 / by Stacy Drake (p.63-68) -- Excavations at Groups B and C, Say Kah, Belize, 2011 / by Sarah E. Jackson and Linda A. Brown (p.69-102) -- Hun Tun Archaeology: Report on the 2011 Field Season / by Robyn L. Dodge (p.103-114) -- Aguada Lagunita Elusiva (RB Lagunita), La Milpa East (RB LME) and Results of the 2011 Explorations along the LaMap East Transect Extension / by Estella Weiss-Krejci and Michael Brandl (p.115-126) -- Towards a Biography Of Place: The 2011 Season of Survey and Excavation at La Milpa North / by Eric J. Heller (p.127-144) -- Phase 2 Research at Wari Camp (RB-56): Summer 2011 / by Laura Levi (p.145-152) -- Summary Report of Investigations at the Site of Dos Hombres: Summer 2011 / by Rissa M. Trachman and Katherine MacDonald (p.153-158) -- Preliminary Report on the 2011 Activities of the Mount Allison University Archaeological Field School in Belize / by Grant R. Aylesworth (p.159-162) -- Tree Species Composition at Medicinal Trail Group A / by Nicholas Brokaw and Sheila Ward (p.163-164) -- Report on Some Stone Tools from RB 18, Northwest Belize: Guijarral and the Chispas Group / by David M. Hyde (p.165)Texas Archeological Research Laborator

Introduction

The purpose of this special issue is to highlight the myriad of applications of geographic information systems within the social sciences. As access to geospatial technologies continues to increase, we are seeing new forms of research that highlight how different approaches to spatial analysis can answer complex questions on topics ranging from contemporary urban policy to ancient civilizations

Mapping Maya Hinterlands: LiDAR Derived Visualization to Identify Small Scale Features in Northwestern Belize

This paper will discuss the processes and methods of relief visualization of LiDAR-derived digital elevation models (DEM’s) and classification of secondary data to identify archaeological remains on the ancient Maya landscape in northwestern Belize. The basis of the research explores various Geographic Information System (GIS) and cartographic techniques to visualize topographical relief. Graphic terrain maps assist archaeologists with predictive settlement patterns. The Relief Visualization Toolbox (RVT 1.3) aids to visualize raster DEM datasets in the predictive identification and interpretation of small-scale archaeological features. This dataset and methodology can be utilized to answer questions of population estimates, mobility costs, and effectiveness of ancient technological agricultural systems

An investigation into the mitochondrial quality control functions of Thorase

Mitochondria play a key role in cell survival due to their importance as key site for ATP production. Maintaining healthy mitochondria is accomplished via multiple quality control mechanisms. One quality attribute to maintain is the proper and timely import of mitochondrial protein. The AAA+ ATPase, Thorase has been identified as a key regulator in maintaining proper import by dislodging protein stuck in the mitochondrial protein importers as well as redirecting mislocalized outer mitochondrial tail-anchored proteins. Separate research has identified Thorase as a key neuroprotective protein acting on synaptic transmission and nutrient dependent mTOR regulation. However, the neuronal specific implications of mitochondrial Thorase function warrant greater investigation. This is especially important given that neurons are highly sensitive to mitochondrial stress given their high energy demands and longevity. In this investigation, the neuroprotective properties of Thorase are investigated with a focus on its mitochondrial function. Mitochondrial processes affected by Thorase are investigated. It is found that Thorase affects cytochrome c release as well as mitochondrial dynamics by dysregulating phosphorylation levels of DRP1 and MFF in HEK cells. A key finding in this investigation is that the effect of Thorase on cellular functions is highly dependent on the cell study being analyzed and on cell stress conditions introduced. The functionality of Thorase appears to be dependent on the needs of the cell. A targeted investigation specifically into Thorase interplay with mitophagy regulators PINK1 and Parkin during PFF induced stress led to conclusion that Thorase is ubiquitinated by Parkin and that this ubiquitination regulates the ability of Thorase to promote mitochondrial quality. The results indicate that Thorase improves mitochondrial import efficiency likely through its interaction with TOM proteins. Parkin ubiquitination of Thorase is potentially leading to degradation of Thorase during PFF induced stress impeding the ability of Thorase to rescue mildly damaged mitochondria. Further investigations are needed to ascertain this effect

Pranlukast Antagonizes CD49f and Reduces Sternness in Triple-Negative Breast Cancer Cells

Introduction: Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs. In the present study, we aimed to repurpose drugs as CD49f antagonists. Materials and Methods: We performed consensus molecular docking using a subdomain of CD49f that is critical for heterodimerization and a collection of pharmochemicals clini-cally tested. Molecular dynamics simulations were employed to further characterize drug-target binding. Using MDA-MB-231 cells, we evaluated the effects of potential CD49f antagonists on 1) cell adhesion to laminin; 2) mammosphere formation; and 3) cell viability. We analyzed the effects of the drug with better CSC-selectivity on the activation of CD49f-downstream signaling by Western blot (WB) and co-immunoprecipitation. Expressions of the stem cell markers CD44 and SOX2 were analyzed by flow cytometry and WB, respectively. Transactivation of SOX2 promoter was evaluated by luciferase reporter assays. Changes in the number of CSCs were assessed by limiting-dilution xenotransplantation. Results: Pranlukast, a drug used to treat asthma, bound to CD49f in silico and inhibited the adhesion of CD49f+ MDA-MB-231 cells to laminin, indicating that it antagonizes CD49f-containing integrins. Molecular dynamics analysis showed that pranlukast binding induces con-formational changes in CD49f that affect its interaction with β1-integrin subunit and constrained the conformational dynamics of the heterodimer. Pranlukast decreased the clonogenicity of breast cancer cells on mammosphere formation assay but had no impact on the viability of bulk tumor cells. Brief exposure of MDA-MB-231 cells to pranlukast altered CD49f-dependent signaling, reducing focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) activation. Further, pranlukast-treated cells showed decreased CD44 and SOX2 expression, SOX2 promoter transacti-vation, and in vivo tumorigenicity, supporting that this drug reduces the frequency of CSC. Conclusion: Our results support the function of pranlukast as a CD49f antagonist that reduces the CSC population in triple-negative breast cancer cells. The pharmacokinetics and toxicology of this drug have already been established, rendering a potential adjuvant therapy for breast cancer patients

An IQSEC2 Mutation Associated With Intellectual Disability and Autism Results in Decreased Surface AMPA Receptors

We have recently described an A350V mutation in IQSEC2 associated with intellectual disability, autism and epilepsy. We sought to understand the molecular pathophysiology of this mutation with the goal of developing targets for drug intervention. We demonstrate here that the A350V mutation results in interference with the binding of apocalmodulin to the IQ domain of IQSEC2. We further demonstrate that this mutation results in constitutive activation of the guanine nucleotide exchange factor (GEF) activity of IQSEC2 resulting in increased production of the active form of Arf6. In a CRISPR generated mouse model of the A350V IQSEC2 mutation, we demonstrate that the surface expression of GluA2 AMPA receptors in mouse hippocampal tissue was significantly reduced in A350V IQSEC2 mutant mice compared to wild type IQSEC2 mice and that there is a significant reduction in basal synaptic transmission in the hippocampus of A350V IQSEC2 mice compared to wild type IQSEC2 mice. Finally, the A350V IQSEC2 mice demonstrated increased activity, abnormal social behavior and learning as compared to wild type IQSEC2 mice. These findings suggest a model of how the A350V mutation in IQSEC2 may mediate disease with implications for targets for drug therapy. These studies provide a paradigm for a personalized approach to precision therapy for a disease that heretofore has no therapy

Toro Times: Raising Our Voices!

During the Spring 2019 semester, Dr. Noah Asher Golden\u27s Teaching of Writing K-12 students partnered with the Journalism class at Yorba Academy for the Arts. Through collaboration over a four-month period, Chapman\u27s future teachers and Yorba\u27s junior high journalists engaged a deep writing process to write a series of features, editorials, and news articles related to a number of global issues. Thank you to Principal Preciado-Martin, former principal Tracy Knibb, Mrs. Andrea Lopez, Mrs. Kori Shelton, and the Lloyd E. and Elisabeth H. Klein Family Foundation for supporting this project.https://digitalcommons.chapman.edu/yorba-chapman/1004/thumbnail.jp

AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF

Umanah et al. show that the S-nitrosylation of Thorase and the transnitrosylation of NSF are responsible for NMDAR-activated trafficking of AMPARs underlying synaptic plasticity. © 2020 The Author(s) The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization of AMPARs from the synaptic membrane. Here, we show that N-methyl-D-aspartate receptor (NMDAR) activation leads to increased S-nitrosylation of Thorase and N-ethylmaleimide-sensitive factor (NSF). S-nitrosylation of Thorase stabilizes Thorase-AMPAR complexes and enhances the internalization of AMPAR and interaction with protein-interacting C kinase 1 (PICK1). S-nitrosylated NSF is dependent on the S-nitrosylation of Thorase via trans-nitrosylation, which modulates the surface insertion of AMPARs. In the presence of the S-nitrosylation-deficient C137L Thorase mutant, AMPAR trafficking, long-term potentiation, and long-term depression are impaired. Overall, our data suggest that both S-nitrosylation and interactions of Thorase and NSF/PICK1 are required to modulate AMPAR-mediated synaptic plasticity. This study provides critical information that elucidates the mechanism underlying Thorase and NSF-mediated trafficking of AMPAR complexes. © 2020 The Author(s)1

Genome sequence and functional genomic analysis of the oil-degrading bacterium Oleispira antarctica

M.K. and P.N.G. designed the work; T.N.C. performed physiological studies; M.K., M.F., Y.A.-R., A.B., N.L.-C., M.E.G., O.R.K., T.Y.N., S.K., I.L., O.V.G., M.M.Y. R.R. and P.N.G. were associated with genome annotation; H.J.H. performed lipids and FAME analysis; M.F., M-l.F., S.J., S.C. and J.P.A performed chaperonin anti-proteome analysis; A.-x. S., O.K., O.E., P.A.P., P.S. and Y.K. were associated with structural proteomics; A.T. and R.F. were associated with functional proteomics; H.L. performed electron microscopy; R.D. performed real-time PCR; M.M.-G. and M.F. performed DIGE proteome analysis; M.G. was involved in siderophore production; O.N.R. performed genomic islands’ analysis; H.T. performed storage lipid compounds’ analysis; P.N.G. coordinated manuscript writing.Accession Codes: The genome sequence of Oleispira antarctica RB-8 has been deposited in GenBank under accession core FO203512. Protein structures have deposited in PDB under accession codes 3QVM (a/b hydrolase, OLEAN_C08020), 3QVQ (phosphodiesterase, OLEAN_C20330), 3M16 (transaldolase, OLEAN_C18160), 3LQY (isochorismatase, OLEAN_C07660), 3LNP (amidohydrolase, OLEAN_C13880), 3V77/3L53 (fumarylacetoacetate isomerase/hydrolase, OLEAN_C35840), 3VCR/3LAB (2-keto-3-deoxy-6-phosphogluconate aldolase, OLEAN_C25130), 3IRU (phoshonoacetaldehyde hydrolase, OLEAN_C33610), 3I4Q (inorganic pyrophosphatase, OLEAN_C30460), 3LMB (protein with unknown function, OLEAN_C10530).Ubiquitous bacteria from the genus Oleispira drive oil degradation in the largest environment on Earth, the cold and deep sea. Here we report the genome sequence of Oleispira antarctica and show that compared with Alcanivorax borkumensis—the paradigm of mesophilic hydrocarbonoclastic bacteria—O. antarctica has a larger genome that has witnessed massive gene-transfer events. We identify an array of alkane monooxygenases, osmoprotectants, siderophores and micronutrient-scavenging pathways. We also show that at low temperatures, the main protein-folding machine Cpn60 functions as a single heptameric barrel that uses larger proteins as substrates compared with the classical double-barrel structure observed at higher temperatures. With 11 protein crystal structures, we further report the largest set of structures from one psychrotolerant organism. The most common structural feature is an increased content of surface-exposed negatively charged residues compared to their mesophilic counterparts. Our findings are relevant in the context of microbial cold-adaptation mechanisms and the development of strategies for oil-spill mitigation in cold environments.We acknowledge the funding from the EU Framework Program 7 to support Projects MAMBA (226977), ULIXES (266473), MAGIC PAH (245226) and MICROB3 (287589) This work received the support of the Government of Canada through Genome Canada and the Ontario Genomics Institute (grant 2009-OGI-ABC-1405 to A.F.Y. and A.S.), and the U.S. Government National Institutes of Health (grants GM074942 and GM094585 (to A.S. through Midwest Center for Structural Genomics). The study was supported by the Max Planck Society and the Deutsche Forschungsgemeinschaft through project KU 2679/2-1 and BU 890/21-1. We thank the sequencing team of the AG Reinhardt for technical assistance and Alfred Beck for computational support. The skilful work of electron microscopic sample preparation by Mrs. Ingeborg Kristen (Dept. VAM, HZI Braunschweig) is gratefully acknowledged. Authors thank Professor Ken Timmis for his critical reading the manuscript and useful comments.http://www.nature.com/naturecommunicationsam201

A comparative study of fortification developments throughout the Maya region and implications of warfare

textThis dissertation presents data to support the continuity of warfare throughout the Maya lowlands, and adjacent regions. I discuss the current problems with the archaeology of warfare, the continuity of conflict beginning with the Late Preclassic through the Terminal Classic. Additionally, I emphasize the influence that Teotihuacan had during the Early Classic throughout Mesoamerica, while in some areas there is evidence of diplomatic and economic relations, there is also clear evidence of forced relations at other sites. Conflict is identified on the archaeological record through the heterarchical analysis of a variety of data encompassing defensive features, settlement patterns, epigraphy, iconography, and forensic data. I examine data from San Jose Mogote, Monte Alban, Montana, Izapa, Kaminaljuyu, and sites located within the northern, central, and southern lowlands. The primary goal is to present a cohesive series of war-related events per lowland zone, and chronological time period. Some of the primary questions deal with how land use, and economic trade relations transform political relations and alliances throughout time. Additionally, how do changes in political alliances affect trade routes? By recognizing the important role warfare played in the lowlands, we also recognize how these events affected the elites and their interaction with other polities, and most importantly how these events affected the commoner populace. In the process of investigating conflict throughout the Preclassic and the Classic periods, we can attempt to pinpoint continuities, political and economic changes, and the sociopolitical responses undertaken by polities in a time of war.Anthropolog