Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms. How excess copper ...induces cell death, however, is unknown. Here, we show in human cells that copper-dependent, regulated cell death is distinct from known death mechanisms and is dependent on mitochondrial respiration. We show that copper-dependent death occurs by means of direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle. This results in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, which leads to proteotoxic stress and ultimately cell death. These findings may explain the need for ancient copper homeostatic mechanisms.
Predictive models are central to both archaeological research and cultural resource management. Yet, archaeological applications of predictive models are often insufficient due to small training data ...sets, inadequate statistical techniques, and a lack of theoretical insight to explain the responses of past land use to predictor variables. Here we address these critiques and evaluate the predictive power of four statistical approaches widely used in ecological modeling-generalized linear models, generalized additive models, maximum entropy, and random forests-to predict the locations of Formative Period (2100-650 BP) archaeological sites in the Grand Staircase-Escalante National Monument. We assess each modeling approach using a threshold-independent measure, the area under the curve (AUC), and threshold-dependent measures, like the true skill statistic. We find that the majority of the modeling approaches struggle with archaeological datasets due to the frequent lack of true-absence locations, which violates model assumptions of generalized linear models, generalized additive models, and random forests, as well as measures of their predictive power (AUC). Maximum entropy is the only method tested here which is capable of utilizing pseudo-absence points (inferred absence data based on known presence data) and controlling for a non-representative sampling of the landscape, thus making maximum entropy the best modeling approach for common archaeological data when the goal is prediction. Regression-based approaches may be more applicable when prediction is not the goal, given their grounding in well-established statistical theory. Random forests, while the most powerful, is not applicable to archaeological data except in the rare case where true-absence data exist. Our results have significant implications for the application of predictive models by archaeologists for research and conservation purposes and highlight the importance of understanding model assumptions.
Bacillus subtilis subsp. subtilis American Type Culture Collection deposit number PTA-125135 has recently been studied by our laboratory as a potential probiotic strain for avian species. The ...objective of the present study was to evaluate growth performance and feed efficiency in broiler chickens in response to a dose titration of the Bacillus strain in feed. In addition to a nonsupplemented control, Bacillus spores were supplemented into broiler chicken diets at 4 levels, which were 8.1 × 104, 1.6 × 105, 2.4 × 105, and 3.2 × 105 CFU per g of feed. The titration was applied to two different dietary regimes of standard or low metabolizable energy (ME), which differed in ME by 22, 56, and 110 kcal/kg in starter, grower, and finisher dietary phases, respectively. All diets contained 249 g per metric ton of a previously patented synbiotic feed additive. Performance data were collected at day 14, 26, and 40 of age, and the effects of Bacillus and ME treatments were evaluated by factorial ANOVA. Treatment group means were further examined for significant (P < 0.05) pairwise differences among treatments and for significant (P < 0.05) linear and quadratic effects. At day 14 of age, significant linear effects for decreased feed conversion ratio (FCR) with higher CFU of Bacillus supplementation were observed within the standard ME diet. At day 26, a linear trend was observed for increased mortality with increased dose within the standard ME diet only. Bacillus supplementation at day 26 also significantly affected FCR and mortality-adjusted FCR, where supplementation with 3.2 × 105 CFU per g feed produced lower FCR and mortality-adjusted FCR than supplementation with 1.6 × 105 CFU per g feed. We conclude from linear effects related to feed efficiency observed at day 14 and from the significant separation of Bacillus treatment means within the titrated range of supplementation at day 26 that further evaluation for effects on performance should be made of doses at 2.4 × 105, 3.2 × 105, and greater CFU per g in feed.
Cholera and the related Escherichia coli-associated diarrheal disease are important problems confronting Third World nations and any area where water supplies can become contaminated. The disease is ...extremely debilitating and may be fatal in the absence of treatment. Symptoms are caused by the action of cholera toxin, secreted by the bacterium Vibrio cholerae, or by a closely related heat-labile enterotoxin, produced by Escherichia coli, that causes a milder, more common traveler's diarrhea. Both toxins bind receptors in intestinal epithelial cells and insert an enzymatic subunit that modifies a G protein associated with the adenylate cyclase complex. The consequent stimulated production of cyclic AMP, or other factors such as increased synthesis of prostaglandins by intoxicated cells, initiates a metabolic cascade that results in the excessive secretion of fluid and electrolytes characteristic of the disease. The toxins have a very high degree of structural and functional homology and may be evolutionarily related. Several effective new vaccine formulations have been developed and tested, and a growing family of endogenous cofactors is being discovered in eukaryotic cells. The recent elucidation of the three-dimensional structure of the heat-labile enterotoxin has provided an opportunity to examine and compare the correlations between structure and function of the two toxins. This information may improve our understanding of the disease process itself, as well as illuminate the role of the toxin in studies of signal transduction and G-protein function.
Avi-Lution® is a defined, patented, synbiotic product containing Saccharomyces cerevisiae, Enterococcus faecium, and Bacillus spp. Broiler chickens (n = 1,250) were experimentally treated as ...uninoculated controls (uCon), inoculated controls (iCon) with Clostridium perfringens, or inoculated and treated with bacitracin methylene disalicylate (BMD) at 55 mg/kg as an infected/treated control or Avi-Lution® at 1.0 (AvL1) or 2.0 (AvL2) g/kg in feed for 42 d. Each treatment was applied to 10 replicate pens of 25 straight-run, newly hatched chicks. Pens treated with AvL1, AvL2, or BMD showed improved growth, feed efficiency, or mortality from necrotic enteritis compared with iCon pens at d 14, 28, and 42. No differences in these measurements, however, were observed between pens treated with AvL1 and AvL2, which suggests that Avi-Lution® was effective at 1.0 g/kg in feed. Despite improved performance, BMD, AvL1, and AvL2 treatments did not decrease the severity of intestinal lesion scores through 42 d of age compared with the infected control. These results demonstrate that Avi-Lution® improved growth performance and feed conversion rates in broilers challenged with Clostridium perfringens despite no difference in severity of intestinal lesion scores.
A series of experiments was conducted to identify the molecular species responsible for surface active emulsification (surfactant) bioactivity in Bacillus subtilis subsp. subtilis strain ATCC ...PTA‐125135, and to describe culture conditions to support the enriched production of said bioactivity in cultured plaque of the strain. The assay for methylene blue active substances (MBAS) was found to be suitable for describing surfactant activity, where a solvent‐extracted molecular fraction from the biofilm was found to retain surfactant activity and positively quantified as MBAS. Furthermore, an HPLC‐refined protein fraction was found to quantify as MBAS with approximately 1·36‐fold or greater surfactant activity per mol than sodium dodecyl sulphate, and a proteomic analysis of solvent extracted residues confirmed that biofilm surface layer protein BslA was a primary constituent of extracted residues. Surfactant bioactivity, quantified as MBAS, was enriched in cultured plaque by the supplementation of culture media with calcium chloride or calcium nitrate.
Significance and Impact of the Study: Surfactants with emulsifying bioactivity are known to be produced by Bacillus subtilis. Here, a colorimetric assay for methylene blue active substances is adapted for use in bacterial plaque to describe surfactant bioactivity, and supplemental salts of calcium during culture are shown to enrich cultured plaque for said bioactivity. Where B. subtilis is utilized as a feed additive to food producing animals, the manufacture of bacterial plaque with controlled and enriched concentration of surfactant bioactivity is desirable, especially where the dose amount is limited by mass, total colony forming units, enzymatic activities or other limiting qualities.
The Basketmaker presence in southern Utah has traditionally been viewed as peripheral to developments originating in the Four Corners region. Far Western Basketmaker Beginnings offers an entirely new ...and provocative perspective—that the origins of farming on the northern Colorado Plateau are instead found far to the west along Kanab Creek.
This volume, based on the results of excavations at Jackson Flat Reservoir south of Kanab, examines a litany of firsts: the earliest Archaic pithouses ever found in this region, evidence that maize farmers arrived here a thousand years earlier than previously reported, and the emergence of a complex Basketmaker farming and foraging culture. Specialists in Far Western Puebloan culture, architecture, settlement patterns, subsistence, chronometry, and prehistoric technologies make a compelling case that farming was introduced to the region by San Pedro immigrants, and that the blending of farmers with local foraging groups gave rise to a Basketmaker lifeway by 200 BC. This book marks a giant leap forward in archaeologists’ understanding of the earliest maize farmers north and west of the Colorado River.
Using a field survey and company data of 170 firms in Singapore, we tested an integrated theoretical model relating CEO transformational leadership (TL), human–capital-enhancing human resource ...management (HRM), and organizational outcomes, including subjective assessment of organizational performance, absenteeism, and average sales. We found that human–capital-enhancing HRM fully mediates the relationship between CEO transformational leadership and subjective assessment of organizational outcomes and partially mediates the relationship between CEO transformational leadership and absenteeism. We discuss practical and theoretical implications.
Winner of the Don D. and Catherine S. Fowler Prize.
In 1931 a group from Harvard University’s Peabody Museum accomplished something that had never been attempted in the history of American ...archaeology: a six-week, four-hundred-mile horseback survey of Fremont prehistoric sites through some of the West’s most rugged terrain. The expedition was successful, but a report on the findings was never completed. What should have been one of the great archaeological stories in American history was relegated to boxes and files in the basement of the Peabody Museum at Harvard.
Now, based on over a thousand pages of documents (field journals, correspondence, and receipts) and over four hundred photographs, this book recounts the remarkable day-to-day adventures of this crew of one professor, five students, and three Utah guides who braved heat, fatigue, and the dangerous canyon wilderness to reveal vestiges of the Fremont culture in the Tavaputs Plateau and Uinta Basin areas. To better tell this story, authors Spangler and Aton undertook extensive fieldwork to confirm the sites; their recent photographs and those of the original expedition are shared on these pages. This engaging narrative situates the 1931 survey and its discoveries within the history of American archaeology.
Click <a href=https://www.suu.edu/apex/2019/01-17-aton.html>here for a podcast with the APEX hour and Jim Aton about The Crimson Cowboys.
PDF
