American skullcap (Scutellaria lateriflora): an ancient remedy for today’s anxiety?

Anxiety is a common but potentially serious disorder as it can lead to somatic and social dysfunction. Orthodox anxiolytics are associated with unpleasant side-effects and dependency. American skullcap (Scutellaria lateriflora) is a popular herb in traditional medicine systems and the western materia medica for anxiety and related disorders. Preliminary clinical and in vitro research provides encouraging support for its potential as a safe, well-tolerated and effective alternative

Synthesis, Structure and Properties of Tetragonal Sr2M3As2O2 (M3 = Mn3, Mn2Cu and MnZn2) Compounds Containing Alternating CuO2-Type and FeAs-Type Layers

Polycrystalline samples of Sr2Mn2CuAs2O2, Sr2Mn3As2O2, and Sr2Zn2MnAs2O2 were synthesized. Their temperature- and applied magnetic field-dependent structural, transport, thermal, and magnetic properties were characterized by means of x-ray and neutron diffraction, electrical resistivity rho, heat capacity, magnetization and magnetic susceptibility measurements. These compounds have a body-centered-tetragonal crystal structure (space group I4/mmm) that consists of MO2 (M = Zn and/or Mn) oxide layers similar to the CuO2 layers in high superconducting transition temperature Tc cuprate superconductors, and intermetallic MAs (M = Cu and/or Mn) layers similar to the FeAs layers in high-Tc pnictides. These two types of layers alternate along the crystallographic c-axis and are separated by Sr atoms. The site occupancies of Mn, Cu and Zn were studied using Rietveld refinements of x-ray and neutron powder diffraction data. The temperature dependences of rho suggest metallic character for Sr2Mn2CuAs2O2 and semiconducting character for Sr2Mn3As2O2 and Sr2Zn2MnAs2O2. Sr2Mn2CuAs2O2 is inferred to be a ferrimagnet with a Curie temperature TC = 95(1) K. Remarkably, we find that the magnetic ground state structure changes from a G-type antiferromagnetic structure in Sr2Mn3As2O2 to an A-type ferrimagnetic structure in Sr2Mn2CuAs2O2 in which the Mn ions in each layer are ferromagnetically aligned, but are antiferromagnetically aligned between layers.Comment: 18 pages, 16 figures, 6 tables; submitted to Phys. Rev.

Functional consequences of sphingomyelinase-induced changes in erythrocyte membrane structure.

Inflammation enhances the secretion of sphingomyelinases (SMases). SMases catalyze the hydrolysis of sphingomyelin into phosphocholine and ceramide. In erythrocytes, ceramide formation leads to exposure of the removal signal phosphatidylserine (PS), creating a potential link between SMase activity and anemia of inflammation. Therefore, we studied the effects of SMase on various pathophysiologically relevant parameters of erythrocyte homeostasis. Time-lapse confocal microscopy revealed a SMase-induced transition from the discoid to a spherical shape, followed by PS exposure, and finally loss of cytoplasmic content. Also, SMase treatment resulted in ceramide-associated alterations in membrane-cytoskeleton interactions and membrane organization, including microdomain formation. Furthermore, we observed increases in membrane fragility, vesiculation and invagination, and large protein clusters. These changes were associated with enhanced erythrocyte retention in a spleen-mimicking model. Erythrocyte storage under blood bank conditions and during physiological aging increased the sensitivity to SMase. A low SMase activity already induced morphological and structural changes, demonstrating the potential of SMase to disturb erythrocyte homeostasis. Our analyses provide a comprehensive picture in which ceramide-induced changes in membrane microdomain organization disrupt the membrane-cytoskeleton interaction and membrane integrity, leading to vesiculation, reduced deformability, and finally loss of erythrocyte content. Understanding these processes is highly relevant for understanding anemia during chronic inflammation, especially in critically ill patients receiving blood transfusions

East-central Florida pre-Columbian wood sculpture: Radiocarbon dating, wood identification and strontium isotope studies

A suite of scientific approaches are applied to four pre- Columbian wood sculptures from east-central Florida, comprising new radiocarbon determinations, wood identification and strontium isotope analysis. The dates for three large zoomorphic carvings recovered from the St. Johns River at Hontoon Island place them between ca. AD 1300 and 1600, suggesting that they belonged to a tradition of erecting largescale pine carvings spanning at least some centuries. Two of the carvings have strontium isotope signals consistent with the immediate vicinity of the site, while the third differs significantly. Baseline data for biologically available strontium from sampled modern trees indicates considerable isotopic variability over short distances, making it difficult to determine the source of the wood used for this third carving. The only anthropomorphic sculpture, recovered from the vicinity of Tomoka State Park, dates to a similar time period, ca. AD 1440-1620. Our study confirms the wood's previous identification as belonging to the genus Peltophorum, a tropical hardwood thought not to be native to Florida. Its strontium isotope value is consistent with its find location, but equally may be found over much of southern Florida, where perhaps the species grew in the past. The results clarify the chronology for a stylistically distinctive carving tradition, as well as raising questions concerning the exchange of organic materials over varying distances. Highlights • 14C results for four east-central Florida carvings (Hontoon Island; Tomoka State Park) range ca. AD 1300-1600, spanning the proto-historic/historic periods • 87Sr/86Sr results for two of the three Hontoon carvings are consistent with the immediate locale, while the third suggests a different provenance • Pinus sp. was used at Hontoon, while Peltophorum sp., currently not native to Florida, was used at Tomoka</p

Aggregation Prediction in Therapeutic Protein Formulations for Excipient Design

Computational Infrastructure & Informatics Poster SessionA major concern in the development therapeutic protein formulations is protein aggregation. Proteins can interact to form bound groups of protein molecules or aggregates. Aggregates in protein formulations reduce effectiveness and can lead to severe immune responses in patients. Excipients are additive molecules that are not therapeutically active, but can increase the stability of protein formulations. An ideal excipient binds with aggregation prone regions on the protein to limit interaction of that region with another protein molecule. The goal of this project is to predict aggregation prone regions and design excipients to interact with these regions. Several tools exist to predict which regions on a protein will be most likely to initiate aggregation. Aggrescan (http://bioinf.uab.es/aggrescan/) and SAP (Spatial Aggregation Potential) were used to predict aggregation prone regions on proteins and the results were compared. Aggrescan uses experimental data to assign each amino acid an aggregation propensity score. An aggregation prone region is identified by a sequence of amino acids with high propensities. The three-dimensional structure is not used in the aggregation prediction. SAP uses molecular simulation to determine regions that are hydrophobic and solvent accessible. Each residue is scored and the results are mapped to the three-dimensional protein structure. A successful prediction tool must use parameters that correlate with aggregation potential for a folded protein. The aggregation prone regions predicted by Aggrescan and SAP were compared to experimental data on protein aggregation. Proteins with a high number of predicted regions or large predicted regions were found to have higher experimental percent aggregation. With the regions identified, molecular simulations were performed for protein-excipient systems. A protein and small molecule docking algorithm was used to determine which regions of the protein certain excipients interacted with. Trehalose, poly(vinylpyrrolidone), and guanadine hydrochloride were used. For an excipient to successfully stabilize a protein and prevent aggregation, the excipient should interact with the aggregation prone regions predicted by Aggrescan and SAP. The predicted regions were compared to the regions where the excipient docks in the molecular simulation. The simulation results were compared to experimental data on the percent aggregation observed in several protein-excipient formulations. The excipients that were found to interact with the predicted aggregation prone regions in simulations should also experimentally prohibit aggregation, leading to lower percent aggregation. Hydrogen-deuterium swapping along with FTIR analysis will be performed experimentally to determine exposed regions on the protein. Proteins with a high number of exposed regions are less stable. The exposed regions will be compared to the aggregation prone regions predicted by Aggrescan and SAP

Avaliação da contagem de ovos por grama de fezes de ovinos infectados com nematóides gastrintestinais e tratados com extratos de Artemisia annua.

O uso intensivo de antiparasitários tem contribuído, a nível mundial, para uma situação de resistência dos parasitas a estes. Muitos princípios ativos comercialmente disponíveis frequentemente não possuem a eficácia desejada em várias propriedades que criam pequenos ruminantes. Conforme levantamentos científicos, (Asteraceae) tem diversas aplicações no campo medicinal, pois possui propriedades anti-inflamatória, sedativa, vermífuga, além de uso no controle da malária. Atualmente, os estudos fitoquímicos de extratos vegetais fornecem informações quanto à natureza dos bioativos, o que pode servir de embasamento para elaboração de formulações antiparasitárias. Este trabalho teve como objetivo primordial verificar a eficácia do extrato diclorometano obtido a partir de no controle antiparasitário ( ) de ovinos. Para a execução do presente estudo, utilizou-se 24 ovinos da raça Santa Inês do rebanho da Embrapa Pecuária Sudeste, localizada em São Carlos, SP, que foram tratados com antihelmíntico e infectados artificialmente com 4.000 larvas (no 3º estágio de desenvolvimento) de . Os animais foram divididos em 4 grupos de 6 animais para os seguintes tratamentos: controle (água), extrato de bicarbonato de sódio de , extrato diclorometano de (ambos via oral, 2g/kg p.v.) e fosfato de levamisol injetável na dose de 4,7 mg/kg. A média de ovos por grama (OPG) de fezes dos grupos no dia zero foi de: 1.741, 1.733, 1.758 e 1.741, respectivamente. Foram realizadas contagens nos dias 3, 7, 10 e 14. A porcentagem de eficácia dos tratamentos realizados foi calculada usando-se o programa RESO para o OPG de fezes do 14° dia dos grupos tratados em relação ao controle. Os dois extratos foram produzidos no Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA) da Unicamp. Detectou-se a presença da artemisinina em 0,6% no extrato de bicarbonato e em 11% do extrato diclorometano. Ao final do experimento (dia 14), pôde-se observar uma redução de 94% do OPG para o grupo levamisol em relação ao controle e de 0% para os extratos vegetais. Concluiu-se que os extratos de não se mostraram eficazes, embora o extrato de diclorometano contivesse uma quantidade elevada de artemisinina. Essa substância é considerada ativa no controle dos parasitas causadores da malária, mas não apresentou eficácia sobre o nematóide gastrintestinal , considerado o mais importante na criação de ovinos

Radiocarbon dating wooden carvings and skeletal remains from Pitch Lake, Trinidad

Since the mid 19th century, rare prehistoric wooden carvings and human skeletal remains have been dredged from Pitch Lake, Trinidad, during commercial asphalt mining. Establishing a chronology for these objects is challenging, due to both a lack of stratigraphic and contextual information and the necessity to completely remove any pitch to ensure accurate radiocarbon dates. A range of solvent extraction protocols was tested to identify the most suitable one for pretreating the Pitch Lake artefacts, and then applied to ten wooden objects and a human cranium recovered from the lake. Several of these objects yielded earlier dates than expected, raising concerns that pitch had remained after pretreatment and had affected the dates. Pyrolysis-GC/MS and optical microscopy techniques were applied to material from the human cranium, a weaving tool, and a small bowl. These techniques, as well as routinely applied laboratory quality assurance procedures, indicated that there was no residual pitch within the cranium or the weaving tool after pretreatment, giving confidence to the dates. However, the small bowl was observed to still be contaminated with pitch after extensive pretreatment, indicating that the date is too old and can only be considered as a terminus post quem

Modeling house price dynamics with heterogeneous speculators

This paper investigates the impact of speculative behavior on house price dynamics. Speculative demand for housing is modeled using a heterogeneous agent approach, whereas ‘real’ demand and housing supply are represented in a standard way. Together, real and speculative forces determine excess demand in each period and house price adjustments. Three alternative models are proposed, capturing in different ways the interplay between fundamental trading rules and extrapolative trading rules, resulting in a 2D, a 3D, and a 4D nonlinear discretetime dynamical system, respectively. While the destabilizing effect of speculative behavior on the model’s steady state is proven in general, the three specific cases illustrate a variety of situations that can bring about endogenous dynamics, with lasting and significant price swings around the ‘fundamental ’ price, as we have seen in many real markets