The West Island Site, 14PH10, A Keith Focus Plains Woodland Site in Kirwin Reservoir Phillips County,Kansas

Abstract

Salvage excavations at a badly eroded site, now an island in the Kirwin Reservoir of west-central Kansas, produced pottery and other artifacts indicative of the Keith Focus. Although the site remains undated, it should fall at ca. A. D. 600.     

Fossil Bison and Artifacts from The Mona Lisa Site,Calgary, Alberta

Abstract

In November, 1968, salvage excavations at the site of an art gallery under construction in urban southwest Calgary, Alberta, Canada, revealed a Paleo-Indian bison kill. The single kill level lay at a depth of more than 250 em. in flood plain deposits of the Bow River, now flowing more than a mile north of the site. The bone bed was overlain by a thick deposit of Mazama Ash (6600 years B.P.). A bone radiocarbon date of 8080 ± 150 years B.P. (G.S.C.-1209) was obtained. Intermittent pedigenesis and fineness of enclosing sediments indicate an overbank flood plain situation for the kill; evidently the site area was repeatedly flooded, probably seasonally, before and after the kill episode. No evidence of a jump-off is present, although this is inconclusive at present. In the 30 square meters excavated at Locality A there was evidence for three activity loci relating to processing of carcasses. The lithic sample includes only crude butchering tools, precluding cultural assignment. Several bone tools, most of them fashioned from tibiae, appear to have been used as expedient and expendable butchering tools at the kill. Some modification of the butchering of lower limbs is noted, apparently to facilitate the production of the bone tools.     

Non-Bison Remains from the Vore Bison Jump,Crook County,Wyoming

Abstract

The Vore. Bison Jump is a multi-component Late-Preh1stonc B1son kill site in the Black Hills of Crook County, Wyoming. Examination of the non Bison revealed a large number of carnivores, mainly wolves. Analysis of these wolf remains showed a need for more careful identification of canid remains from archaeological sites in light of incipient domestication of wolves at this site.     

A Preliminary Report on Two Sites at Piney Creek,Wyoming 48J03Ll and 48J031

Abstract

During the summer of 1964, the University of Wyoming and the Wyoming Archaeological Society conducted exploratory excavations in two sites near Buffalo, Wyoming. Site 48J03ll consists of a number of stone circles and is apparently a camp site and site 48J0312 is a bison kill and butchering site. Artifact assemblages suggest an affiliation with late prehistoric and early historic sites in the Yellowstone River drainage.     

A Plainview Kill/Butchering Locale On The Llano Est Acado-The Lubbock Lake Site

Abstract

The Lubbock Lake site is a multi-component, stratified locality on the Llano Estacada (Southern High Plains). Part of a Plainview (Paleo-Indian) period bison kill/butchering locale is being excavated. Cultural designation is based on recovered projectile points, stratigraphic position, and radiocarbon dates. Tool assemblage consists of lithic and bone expediency tool kits. Geological, faunal, and paleoenvironmental settings create an interpretative framework for the cultural event. Only part of the Plainview lifeway system is reflected at the site. The locale represents a different level of social organization than seen at other Plainview period bison kill sites. Preliminary statements include a few differences and similarities between excavated Plainview sites.     

WATER TEMPERATURE AND THE 1987 FISH KILL AT LAKE ST LUCIA ON THE SOUTH EASTERN COAST OF AFRICA

Summary

An unusually cold spell during the winter of 1987 caused a drop in water temperature at Lake St Lucia. This coupled with typical estuarine salinities in the lake resulted in a fish kill. The kill was one of the largest recorded in a South African estuarine environment and involved an estimated 250,000 fish comprising at least 21 species. Most fish that died belonged to small species. Densities of dead fish recorded along the lake's shoreline ranged from 0.1 to 16.6 fish per metre. It is concluded that the combination of low water temperature and near marine salinities was the major cause of the 1987 fish kill at Lake St Lucia.     

Late Paleo-Indian Activity At The Lubbock Lake Site

Abstract

Excavations at Lubbock Lake (41 LU1), Southern High Plains of Texas, revealed the presence of a complex, late Paleo-Indian feature containing a camping area and bison (Bison antiquus) kill/butchering locale. The feature is found within a cienega or marsh deposit and dates from 8300 to 8600 years. At least two camping episodes are indicated, separated by the kill/butchering event. Camp debris consists of a projectile point midsection, unifacial and bifacial tools, and flakes. Faunal debris includes remains of butchered pronghorn antelope, rabbits, ducks, grouse, and turtles. The kill/butchering locale contains remains of four bison and three fetuses, a bone expediency tool, a reworked projectile point base, unifacial butchering tools, and flakes. Projectile points, other lithic tools, and age of the feature indicate a Firstview occupation. From faunal and geologic data, site environs are reconstructed as a marshlands rimmed by a narrow border of wet meadows grading into a mixed grass prairie. Although several late Paleo-Indian kill/butchering locales are known on the Southern High Plains, this feature is the first late Paleo-Indian camp.     

The Bentzen-Little Bald Mountain Site

Abstract

Excavation of a campsite and kill site area situated on a natural animal crossing or saddle between the North Fork of the Tongue River and Beaver Creek just south of Little Bald Mountain, Wyoming, at an elevation of 9,000 feet is described. Among the features found were two firepits containing burned rock, animal bones, and artifacts. The amount of artifacts and animal bones recovered suggested a long and/or intensive occupation, The bones included those of elk and mountain sheep, intermixed with teeth.     

On The Significance of Additional Radiocarbon Dates from Bonfire Shelter,Texas

Abstract

Two hitherto unreported dates from charcoal samples associated with remains attributed to a Paleo-Indian bison kill at this site are provided. These dates further substantiate a minimal antiquity of ca. 10,000 years for the deposit and, by inference, give evidence of the use of a “bison jump” technique of hunting at this early time period. Definitional problems, differing views on the antiquity, basic comparability of cited examples, and temporal continuity of this mode of mass killing are briefly discussed. Some suggestions are made as to the cultural implications made probable by acceptance of an early date for this practice.     

Epidemiología de las fungemias en un hospital pediátrico de alta complejidad

BackgroundA retrospective study on the epidemiology of fungaemia due to yeasts of medical importance at the Hospital Nacional de Pediatría Prof. Dr. J. Garrahan, Buenos Aires was conducted between September 2001 and September 2003.ObjectivesTo learn the distribution of yeast species and to evaluate their in vitro antifungal susceptibility profile.MethodsThe minimum inhibitory concentration (MIC) was determined according to the CLSI M27-A2 procedure, and time kill curves against amphotericin B were also performed.Results-ConclusionsThe species isolated were Candida parapsilosis (32.6% of isolates); Candida albicans (26.5%), Candida tropicalis (24.5%), and other yeasts (16.4%). Candida isolates were susceptible to the antifungals evaluated, but amphotericin B-tolerant isolates were detected using time kill curves.     

Docking and DFT Studies to explore the Topoisomerase II ATP Pocket employing 3-Substituted 2,6-Piperazindiones for drug design

Topoisomerases (Topos) are very important protein targets for drug design in cancer treatment. Human Topo type IIα (hTopo IIα) has been widely studied experimentally and theoretically. Here, we performed protein rigid/flexible side-chain docking to study a set of thirty-nine 3-substituted-2,6-piperazindiones (labelled 1a, (R)-[(2–20)a] and (S)-[(2–20)b]) derived from α-amino acids. To explain the ligand–protein complexes at the electronic level [using the highest occupied and the lowest unoccupied molecular orbitals (HOMO and LUMO) energies], density functional theory calculations were carried out. Finally, to show adenosine triphosphate (ATP) binding-site constituents, the Q-SiteFinder program was used. The docking results showed that all of the test compounds bind to the ATP-binding site on hTopo IIα. Recognition is mediated by the formation of several hydrogen bond acceptors or donators. This site was the largest (631 Å³) according to the Q-SiteFinder program. When using the protein rigid docking protocol, compound 13a derived from (R)-Lys showed the highest affinity. However, when a flexible side-chain docking protocol was used, the compound with the highest affinity was 16a, derived from (R)-Trp. Frontier molecular orbital studies showed that the HOMO of the ligand interacts with the LUMO located at side-chain residues from the protein-binding site. The HOMO of the binding site interacts with the LUMO of the ligand. We conclude that some ligand properties including the hindrance effect, hydrogen bonds, π–π interactions and stereogenic centres are important for the ligand to be recognised by the ATP-binding site of hTopo IIα.     

Trapping tunnel design incorporating behavioural preferences of stoats

Abstract

Stoats (Mustela erminea) are introduced pests in New Zealand, and there is an urgent need for effective trapping systems that kill the animal in a humane manner. A treadle trap was designed, the Dominus trap, that utilised an earlier‐proven humane killing system enhanced by the addition of a treadle plate trigger. This system enabled the trap to be classified as a Class A trap under the National Animal Welfare Advisory Committee (NAWAC) guidelines for animal kill traps, by successfully rendering 10/10 animals unconscious within 30 s. The Dominus trap mimics a tunnel, which by its very shape entices the animal to enter, but weighs only 600 g. Atrial at Flea Bay, on Banks Peninsula, used 35 Dominus traps placed alternately between 35 Fenn Mk VI traps set over 3150 trap nights (TN). The trial was conducted from March to May 2007 and was repeated for a further 7740 trap nights from January to March 2008, using 20 Dominus traps. The Dominus trap caught stoats consistently at the rate of 0.22 stoats/100 TN in both years, compared with 0 and 0.14/100 TN in Fenn traps, so potentially provides a humane alternative to the Fenn.     

Biotransformation of pseudolaric acid B by Chaetomium globosum

Pseudolaric acid B (1) is a natural product with potent antifungal activity. We discovered that pseudolaric acid B did not kill but only suppress the growth of the filamentous fungus Chaetomium globosum. It was proposed that pseudolaric acid B was converted to metabolites with decreased antifungal activities. In this study, a scaled-up biotransformation of pseudolaric acid B by C. globosum produced five metabolites, including three new compounds, pseudolaric acid I (2), pseudolaric acid B 18-oyl-alanine (4) and pseudolaric acid B 18-oyl-serine (6), together with two known compounds, pseudolaric acid F (3) and pseudolaric acid B 18-oyl-glycine (5). The structures were characterized by NMR and MS spectroscopy. The major biotransformation reaction was conjugation with amino acids. None of the metabolites showed inhibitory effects on the growth of Candida albicans. The results suggested that biotransformation might be a detoxification process for fungi to resist antifungal drugs.     

3ircular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen

Purpose: The purpose of this study was to confirm the hypothesis that a site-II-to-site-I displacement takes place when some nonsteroidal anti-inflammatory drugs are displaced by another drug from their high-affinity binding site to a site of lower affinity on human serum albumin (HSA).Methods: Diclofenac, sodium salt, was used as a representative example because of its prominent reversal of the Cotton effect. Effects of site-specific drugs on the free fraction of diclofenac were determined by equilibrium dialysis, and effects on induced circular dichroism (CD) of diclifenac bound to HSA were studied by CD and CD simulation techniques.Results: Ibuprofen, a site-II-specific drug, altered the CD spectrum of the diclofenac-HSA complex at a molar ratio of 0.5∶1 to that obtained at a higher ratio (5∶1) without ibuprofen. The induced CD spectrum obtained in the presence of ibuprofen was very similar to one that assumed that all diclofenac displaced from its high-affinity binding site (site II) became rebound to a lower-affinity site (site I). The rebinding could be influenced by a free energy linkage between the two sites which would make site I (or parts thereof) more suitable for diclofenac binding.Conclusion: We have confirmed the existence of a site II-to-site displacement, which is very striking and pharmacologically important, because the concentration of unbound drug being displaced is much lower than expected for a competitive mechanism.     

Structural investigation and inhibitory response of halide on phosphoserine aminotransferase from Trichomonas vaginalis

BackgroundPhosphoserine aminotransferase (PSAT) catalyses the second reversible step of the phosphoserine biosynthetic pathway in Trichomonas vaginalis, which is crucial for the synthesis of serine and cysteine.MethodsPSAT from T. vaginalis (TvPSAT) was analysed using X-ray crystallography, enzyme kinetics, and molecular dynamics simulations.ResultsThe crystal structure of TvPSAT was determined to 2.15 Å resolution, and is the first protozoan PSAT structure to be reported. The active site of TvPSAT structure was found to be in a closed conformation, and at the active site PLP formed an internal aldimine linkage to Lys 202. In TvPSAT, Val 340 near the active site while it is Arg in most other members of the PSAT family, might be responsible in closing the active site. Kinetic studies yielded Km values of 54 μM and 202 μM for TvPSAT with OPLS and AKG, respectively. Only iodine inhibited the TvPSAT activity while smaller halides could not inhibit.ConclusionResults from the structure, comparative molecular dynamics simulations, and the inhibition studies suggest that iodine is the only halide that can bind TvPSAT strongly and may thus inhibit the activity of TvPSAT.The long loop between β8 and α8 at the opening of the TvPSAT active site cleft compared to other PSATs, suggests that this loop may help control the access of substrates to the TvPSAT active site and thus influences the enzyme kinetics.General significanceOur structural and functional studies have improved our understanding of how PSAT helps this organism persists in the environment.     

The Scoggin Site: a Study in Mckean Typology

Abstract

The Scoggin Site, an Early Middle Period Bison kill in south-central Wyoming, yielded two distinct stylized projectile point varieties from the one bone layer present. This single component affords optimum opportunity to study the two varieties of points in one context. The technology for the projectile point assemblage is described, and literature concerning the deep side-notched Early Middle Period or Archaic age points from the Northwestern Plains and the northern Great Basin is discussed.

In order to discover if the deep side-notched projectile points from Scoggin (reminiscent of much later projectile point types) were indeed part of the McKean classification, their dimensions were compared to those of the indented base McKean lanceolate projectile points from the same site. The measurements overlap or can be otherwise explained for both lanceolate and side-notched forms. The Statistical Package for the Social Sciences (SPSS) was used to demonstrate that the two types of points are quite homogeneous.

The question as to why the points differ stylistically has several possible answers. For example, the two types may represent interacting but identifiable ethnic groups, or the numerical superiority of the side-notched point may reflect hafting superiority. At any rate, the deep side-notched point is an integral part of the Early Middle Period and can be classified as McKean.     

Gene therapy with cytokine-transfected xenogenic cells (Vero-IL-2) in patients with metastatic solid tumors: mechanism(s) of elimination of the transgene-carrying cells

Eleven patients with advanced cancer were treated in a clinical gene therapy trial by repeated intra- tumoral injections with different doses of xenogenic fibroblasts secreting high amounts of human interleukin-2 (Vero-IL2). Treatments in a total of 14 courses were well tolerated and resulted in clinical responses and measurable biological effects. Together with increases in serum interleukin-2 (IL-2), modifications of the V-β T cell receptor repertoire and induction of intratumoral T-cell infiltration were observed. When the intratumoral expression of endogenous cytokine genes and the persistence of the IL-2 transgene at the application site and in peripheral blood were investigated, rapid disappearance of the transgene at the application site appeared to be the most prominent biological effect. Tests detecting a single Vero-IL2 cell against a background of 10⁵ non-transfected cells were not able to demonstrate significant expression of exogenous IL-2 (i.e. the transgene or transgene-carrying cells) in tumor biopsies or blood at different times. Therefore, further studies were performed to evaluate the mechanism(s) involved in the rapid disappearance of xenogenic carrier cells in more detail. We show here that significant in vitro cytotoxicity against transgene-carrying Vero cells can be observed in peripheral blood of all the patients before treatment as well as in healthy controls. “Cold” target inhibition shows that significant killing of Vero-IL2 cells is mediated by natural killer (NK) cells. This was confirmed by showing that established CD3⁻/CD16 ⁺ /CD56 ⁺ peripheral blood NK cell clones kill both K562 and Vero-IL2 target cells. The failure of other mechanisms (complement, antibody-dependent cell cytotoxicity or cytotoxic T lymphocytes) to destroy xenogenic, histoincompatible Vero cells in vitro suggests that NK cells also might be responsible for the killing of Vero-IL2 in vivo and for the failure to detect the transgene at the application site. These results might also be of importance for some aspects of the current discussion of xenotransplantation. Received: 9 April 1999 / Accepted: 14 June 1999     

Toward Developing a Universal Treatment for Fungal Disease Using Radioimmunotherapy Targeting Common Fungal Antigens

Background

Previously, we demonstrated the ability of radiolabeled antibodies recognizing the cryptococcal polysaccharide capsule to kill Cryptococcus neoformans both in vitro and in infected mice. This approach, known as radioimmunotherapy (RIT), uses the exquisite ability of antibodies to bind antigens to deliver microbicidal radiation. To create RIT reagents which would be efficacious against all major medically important fungi, we have selected monoclonal antibodies (mAbs) to common surface fungal antigens such as heat shock protein 60 (HSP60), which is found on the surface of diverse fungi; beta (1,3)-glucan, which is a major constituent of fungal cell walls; ceramide which is found at the cell surface, and melanin, a polymer present in the fungal cell wall.

Methods

MAbs 4E12, an IgG2a to fungal HSP60; 2G8, an IgG2b to beta-(1,3)-glucan; and 6D2, an IgM to melanin, were labeled with the alpha particle emitting radionuclide 213-Bismuth (²¹³Bi) using the chelator CHXA”. B11, an IgM antibody to glucosylceramide, was labeled with the beta emitter 188-Rhenium (¹⁸⁸Re). Model organisms Cryptococcus neoformans and Candida albicans were used to assess the cytotoxicity of these compounds after exposure to either radiolabeled mAbs or controls.

Results

²¹³Bi-mAbs to HSP60 and to the beta-(1,3)-glucan each reduced the viability of both fungi by 80–100%. The ²¹³Bi-6D2 mAb to melanin killed 22% of C. neoformans, but did not kill C. albicans. B11 mAb against fungal ceramide was effective against wild-type C. neoformans, but was unable to kill a mutant lacking the ceramide target. Unlabeled mAbs and radiolabeled irrelevant control mAbs caused no killing.

Conclusion

Our results suggest that it is feasible to develop RIT against fungal pathogens by targeting common antigens and such an approach could be developed against fungal diseases for which existing therapy is unsatisfactory.

     

Identification of potential allosteric communication pathways between functional sites of the bacterial ribosome by graph and elastic network models

BackgroundAccumulated evidence indicates that bacterial ribosome employs allostery throughout its structure for protein synthesis. The nature of the allosteric communication between remote functional sites remains unclear, but the contact topology and dynamics of residues may play role in transmission of a perturbation to distant sites.Methods/resultsWe employ two computationally efficient approaches – graph and elastic network modeling to gain insights about the allosteric communication in ribosome. Using graph representation of the structure, we perform k-shortest pathways analysis between peptidyl transferase center-ribosomal tunnel, decoding center-peptidyl transferase center - previously reported functional sites having allosteric communication. Detailed analysis on intact structures points to common and alternative shortest pathways preferred by different states of translation. All shortest pathways capture drug target sites and allosterically important regions. Elastic network model further reveals that residues along all pathways have the ability of quickly establishing pair-wise communication and to help the propagation of a perturbation in long-ranges during functional motions of the complex.ConclusionsContact topology and inherent dynamics of ribosome configure potential communication pathways between functional sites in different translation states. Inter-subunit bridges B2a, B3 and P-tRNA come forward for their high potential in assisting allostery during translation. Especially B3 emerges as a potential druggable site.General significanceThis study indicates that the ribosome topology forms a basis for allosteric communication, which can be disrupted by novel drugs to kill drug-resistant bacteria. Our computationally efficient approach not only overlaps with experimental evidence on allosteric regulation in ribosome but also proposes new druggable sites.     

Nutrient supply in undrained and drained Calthion meadows

Abstract. Plant species-rich Calthion meadows on mesotrophic fen peat soil extensively cut for hay are among the endangered semi-natural vegetation types in northwestern Europe. They are often badly affected by lowering the groundwater table (drainage) and fertilization. In a comparative study of an undrained site with a Calthion meadow and an adjacent drained site, availability of N, P and K was biologically assessed under field conditions (for two years) as well as in a greenhouse (for 18 weeks) by measuring shoot responsiveness. Also, experimental wetting of intact turf samples taken from both sites was applied in order to study the interaction between nutrient supply and anaerobic soil conditions. It was concluded that the above-ground phytomass yield in the undrained site was restricted by a major shortage of N-supply and a moderate shortage of K-supply by the fen peat soil. The above-ground phytomass yield of the drained site was only reduced by a strongly limited supply of K by the soil. The extent of K-deficiency was larger for the drained site. No P-deficiency was observed in any of the drained or undrained sites. Rewetting turf samples, taken from the drained site, did not change above-ground phytomass yields, suggesting that nutrient supplies were not affected by rewetting. Leaching has likely resulted in a strong reduction of K-supply in the drained site. It is assumed that a shortage in K-supply from the peat soil may have become an important environmental constraint for characteristic plant species of Calthion meadows. This may hamper the development of this meadow type on drained peat soils after rewetting by groundwater discharge.