Michael Adler

Ancestral pueblo population aggregation and abandonment in the North American Southwest

After over a century of archaeological research in the American Southwest, questions focusing on population aggregation and abandonment continue to preoccupy much of Pueblo archaeology. This article presents a historical overview of the present range of explanatory approaches to these two processes, with a primary focus on population aggregation in those regions occupied by historic and prehistoric Pueblo peoples. We stress the necessarily complementary nature of most of these explanations of residential abandonment and aggregation. Case studies from the northern Southwest illustrate the continuous nature of these processes across time and space. We suggest that additional explanatory potential will be gained by the use of well-defined theoretical units to frame our current approaches. We extend the use of the “local community” concept as a theoretical unit of organization that, along with explicit archaeological correlates, should help advance our research into population aggregation and abandonment in this and other regions of the world.

The Zinc-Dependent Protease Activity of the Botulinum Neurotoxins

The botulinum neurotoxins (BoNT, serotypes A-G) are some of the most toxic proteins known and are the causative agents of botulism. Following exposure, the neurotoxin binds and enters peripheral cholinergic nerve endings and specifically and selectively cleaves one or more SNARE proteins to produce flaccid paralysis. This review centers on the kinetics of the Zn-dependent proteolytic activities of these neurotoxins, and briefly describes inhibitors, activators and factors underlying persistence of toxin action. Some of the structural, enzymatic and inhibitor data that are discussed here are available at the botulinum neurotoxin resource, BotDB (http://botdb.abcc.ncifcrf.gov).

The Changing Scale and Configuration of Mesa Verde Communities

ABSTRACT Comparative demographic analyses of nine locations across the Northern San Juan region reveal highly variable population growth rates between A.D. 900 and 1300. We used both fixed and increasing site use life estimates to measure population density and to estimate the size of individual residential communities for the early Pueblo II through late Pueblo III periods. The results reveal that population density increased in the more agriculturally productive central Mesa Verde region but remained stable or declined on its peripheries. Over time, the central Mesa Verde region underwent varied demographic changes, including brief periods of rapid growth; we argue that these brief periods were the result of small-scale, local migrations that reflected shifts in the sociopolitical landscape, rather than concerns with local environmental productivity. Additional analyses of community organization suggests that relatively small and dispersed sites made up an important part of the Mesa Verde region social landscape even after the formation of nucleated villages.

How a Neurotoxin Survives

Botulinum neurotoxin must form a complex with a structurally similar protein to survive in the gastrointestinal tract. Botulinum neurotoxins are secreted by the spore forming Gram-positive bacteria Clostridium botulinum and some other Clostridium strains under suitable anaerobic conditions (1). Ingestion or inhalation of botulinum neurotoxin leads to a severe neuroparalytic disease, termed botulism, which is characterized by muscle paralysis and autonomic dysfunction. Both conditions stem from inhibition of acetylcholine release, which results from botulinum neurotoxin-mediated proteolysis of one of three SNARE (soluble N-ethylmaleimide–sensitive factor attachment protein receptor) proteins involved in the release of this neurotransmitter from nerve terminals (2). On page 977 of this issue, Gu et al. (3) provide a key insight into how botulinum neurotoxin can survive passage through the gastrointestinal tract, allowing the intact toxin to reach the bloodstream.

Kinetic and Reaction Pathway Analysis in the Application of Botulinum Toxin A for Wound Healing

A relatively new approach in the treatment of specific wounds in animal models and in patients with type A botulinum toxin is the focus of this paper. The indications or conditions include traumatic wounds (experimental and clinical), surgical (incision) wounds, and wounds such as fissures and ulcers that are signs/symptoms of disease or other processes. An objective was to conduct systematic literature searches and take note of the reactions involved in the healing process and identify corresponding pharmacokinetic data. From several case reports, we developed a qualitative model of how botulinum toxin disrupts the vicious cycle of muscle spasm, pain, inflammation, decreased blood flow, and ischemia. We transformed this model into a minimal kinetic scheme for healing chronic wounds. The model helped us to estimate the rate of decline of this toxins therapeutic effect by calculating the rate of recurrence of clinical symptoms after a wound-healing treatment with this neurotoxin.

Yesterday and Today: The Impact of Research Conducted at Camp Detrick on Botulinum Toxin

Introduction This review summarizes the research conducted on botulinum toxin (BoTx) from 1943 to 1956 by a small group of Camp Detrick investigators and their staff. A systematic, cross-disciplinary approach was used to develop effective vaccines against this biological warfare threat agent. In response to the potential need for medical countermeasures against BoTx during World War II, the refinement of isolation and purification techniques for BoTx successfully led to the large-scale production of botulinum toxoid vaccines. In addition, the work at Camp Detrick provided the foundation for the subsequent use of BoTx as a tool for studying the trophic regulation of skeletal muscle within motor neuron terminals and, more recently, for elucidation of the intricate details of neurotransmitter release at the molecular level. Indirectly, Camp Detrick investigators also played a significant role in studies that culminated in the use of BoTx as a pharmaceutical product that has been approved by the U.S. Food and Drug Administration for treating movement disorders, autonomic dysfunctions, and other conditions. Methods Online literature searches were performed with Google, Google Scholar, PubMed, the bibliography from the Camp Detrick technical library, and at the Defense Technical Information Center. Reference lists in some of the primary research publications and reviews also provided source material. Search terms included botulinum, botulinus, and Camp Detrick. References related to the subsequent impacts of the Camp Detrick results were selected and cited from reviews and primary references in the more recent literature. Notes on toxin nomenclature and potential sources of error in this study are presented. Results The literature searches returned 27 citations of Camp Detrick authors, 24 of which were articles in peer-reviewed journals. The publications by these investigators included several disciplines such as biochemistry, immunology, pharmacology, physiology, and toxicology. A fundamental finding was the identification of critical nutritional components for improved growth of Clostridium botulinum and the increased production of BoTx serotype A. The purification processes that were developed at Camp Detrick allowed for the production of crystalline material to be scaled up for the manufacture of toxoid vaccine. Based on the research by Camp Detrick scientists, a toxoid supply of over 1 million units was available to vaccinate ~300,000 troops before the large-scale operations of D-Day. Conclusions BoTx research during the period 1943 to 1956 resulted in refinements in the techniques for isolating and purifying the crystalline BoTx type A. These results led to the development and manufacture of a toxoid vaccine that was available in a sufficient quantity to protect ~300,000 warfighters in a large-scale military operation. One of the most important long-term consequences derived from the knowledge gained by the efforts at Camp Detrick was the development in the 1980s of safe and effective therapeutic uses for BoTx type A, the most lethal biological substance known.

Botulinum neurotoxin detection methods for public health response and surveillance

Botulism outbreak due to consumption of food contaminated with botulinum neurotoxins (BoNTs) is a public health emergency. The threat of bioterrorism through deliberate distribution in food sources and/or aerosolization of BoNTs raises global public health and security concerns due to the potential for high mortality and morbidity. Rapid and reliable detection methods are necessary to support clinical diagnosis and surveillance for identifying the source of contamination, performing epidemiological analysis of the outbreak, preventing and responding to botulism outbreaks. This review considers the applicability of various BoNT detection methods and examines their fitness-for-purpose in safeguarding the public health and security goals.