Assessment of In-House Natural Product and Synthetic Compound Libraries Based on In vitro Inhibition of Cholinesterases

The first line medication for mild to moderate Alzheimer s disease (AD) is based on cholinesterase inhibitors which prolong the effect of the neurotransmitter acetylcholine in cholinergic nerve synapses which relieves the symptoms of the disease. Implications of cholinesterases involvement in disease modifying processes has increased interest in this research area. The drug discovery and development process is a long and expensive process that takes on average 13.5 years and costs approximately 0.9 billion US dollars. Drug attritions in the clinical phases are common due to several reasons, e.g., poor bioavailability of compounds leading to low efficacy or toxic effects. Thus, improvements in the early drug discovery process are needed to create highly potent non-toxic compounds with predicted drug-like properties. Nature has been a good source for the discovery of new medicines accounting for around half of the new drugs approved to market during the last three decades. These compounds are direct isolates from the nature, their synthetic derivatives or natural mimics. Synthetic chemistry is an alternative way to produce compounds for drug discovery purposes. Both sources have pros and cons. The screening of new bioactive compounds in vitro is based on assaying compound libraries against targets. Assay set-up has to be adapted and validated for each screen to produce high quality data. Depending on the size of the library, miniaturization and automation are often requirements to reduce solvent and compound amounts and fasten the process. In this contribution, natural extract, natural pure compound and synthetic compound libraries were assessed as sources for new bioactive compounds. The libraries were screened primarily for acetylcholinesterase inhibitory effect and secondarily for butyrylcholinesterase inhibitory effect. To be able to screen the libraries, two assays were evaluated as screening tools and adapted to be compatible with special features of each library. The assays were validated to create high quality data. Cholinesterase inhibitors with various potencies and selectivity were found in natural product and synthetic compound libraries which indicates that the two sources complement each other. It is acknowledged that natural compounds differ structurally from compounds in synthetic compound libraries which further support the view of complementation especially if a high diversity of structures is the criterion for selection of compounds in a library.

Molecular phylogeny of Hemidactylus geckos (Squamata: Gekkonidae) of the Indian subcontinent reveals a unique Indian radiation and an Indian origin of Asian house geckos

Represented by approximately 85 species, Hemidactylus is one of the most diverse and widely distributed genera of reptiles in the world. In the Indian subcontinent, this genus is represented by 28 species out of which at least 13 are endemic to this region. Here, we report the phylogeny of the Indian Hemidactylus geckos based on mitochondrial and nuclear DNA markers sequenced from multiple individuals of widely distributed as well as endemic congeners of India. Results indicate that a majority of the species distributed in India form a distinct clade whose members are largely confined to the Indian subcontinent thus representing a unique Indian radiation. The remaining Hemidactylus geckos of India belong to two other geographical clades representing the Southeast Asian and West-Asian arid zone species. Additionally, the three widely distributed, commensal species (H. brookii, H. frenatus and H. flaviviridis) are nested within the Indian radiation suggesting their Indian origin. Dispersal-vicariance analysis also supports their Indian origin and subsequent dispersal out-of-India into West-Asian arid zone and Southeast Asia. Thus, Indian subcontinent has served as an important arena for diversification amongst the Hemidactylus geckos and in the evolution and spread of its commensal geckos. (C) 2010 Elsevier Inc. All rights reserved.

Standardization of pollen allergens of Parthenium hysterophoms and selection of an in-house reference extract

A standardized in-house reference extract from the pollen of Parthenium hysterophorus, which is responsible for the high incidence of allergic rhinitis in India, was generated and examined by skin test, radio-allergosorbent test inhibition and isoelectric focusing. Parthenium reference allergen discs and positive reference serum were also generated. These reference reagents could not only be used for the quantitation of Parthenium-specific IgE in the sera of rhinitis patients but also for the evaluation of allergenic activity (relative potency and lot-to-lot variation) of different batches of Parthenium pollen.

Extracting Three Dimensional Surface Model of Human Kidney from the Visible Human Data Set using Free Software

Three dimensional digital model of a representative human kidney is needed for a surgical simulator that is capable of simulating a laparoscopic surgery involving kidney. Buying a three dimensional computer model of a representative human kidney, or reconstructing a human kidney from an image sequence using commercial software, both involve (sometimes significant amount of) money. In this paper, author has shown that one can obtain a three dimensional surface model of human kidney by making use of images from the Visible Human Data Set and a few free software packages (ImageJ, ITK-SNAP, and MeshLab in particular). Images from the Visible Human Data Set, and the software packages used here, both do not cost anything. Hence, the practice of extracting the geometry of a representative human kidney for free, as illustrated in the present work, could be a free alternative to the use of expensive commercial software or to the purchase of a digital model.

Ad valorem housing subsidies may reduce house building

In this paper it is shown that an ad valorem housing subsidy set by a central regulator (or a raise in the ad valorem housing subsidy rate) may reduce the number of houses built in the market and increase the price paid by the buyers of houses. The analysis considers a situation where there is imperfect competition in the housing market and a local regulator that decides on density, or on the number of sites for housing development, and that cares about a combination of the profits of housing developers and the surplus of buyers of houses.

Ras Behari’s guide to buying fish seed

Document contains 4 pages.

Influence of Dilute Acetic Acid Treatments on Survival of Monoecious Hydrilla Tubers in the Oregon House Canal, California

Hydrilla (Hydrilla verticillata (L.f.)Royle), a serious aquatic weed, reproduces through formation of underground tubers. To date, attacking this life-cycle stage has been problematic. The purpose of this study was to measure the impact of exposure to dilute acetic acid on monoecious hydrilla tubers under field conditions. In this field experiment, treatments were acetic acid concentration (0, 2.5, or 5%) and sediment condition (perforated or not perforated). Each of 60, 1x1 m plots (in the Oregon House Canal) were randomly assigned to one treatment. Two weeks after treatment, we collected three samples from each plot. One was washed over 2 mm wire mesh screens to separate tubers from sediment. Relative electrolyte leakage was measured for one tuber from each plot. Five additional tubers from each plot were placed in a growth chamber and sprouting monitored for four weeks. A second sample from each plot was placed in a plastic tub and placed in an outdoor tank, filled with water. These samples were monitored for tuber sprouting. Relative electrolyte leakage increased significantly for tubers exposed to 2.5% or 5% acetic acid. Effects on tubers in perforated sediment were reduced. Exposure to acetic acid inhibited tuber sprouting by 80 to 100%, in both chamber and outdoor tests. These results confirm findings from earlier laboratory/greenhouse experiments, and suggest that this approach may be useful in the management of hydrilla tuber banks in habitats where the water level can be lowered to expose the sediments.

Camino a la jubilación: alquiler versus compra de vivienda

Las previsiones del número de personas mayores en España para el año 2050 se han disparado. Un aumento de la población mayor que supondrá grandes dificultades para un sistema público de pensiones cuya viabilidad está en duda. España es un país en el que la cultura del ahorro a través de la vivienda en propiedad está muy arraigada. Sin embargo, en la actualidad existe un auge de las personas que optan por el alquiler como forma de residencia. Por ello, durante este trabajo se analiza la vida de una persona que optará bien por la compra de una vivienda o bien por el alquiler de una vivienda para complementar su futura pensión pública. Mediante la compra de vivienda, y una vez amortizado el préstamo hipotecario que deberá soportar, se le presentaran los productos denominados vivienda pensión e hipoteca inversa para financiar las posibles necesidades que puedan surgir en su jubilación. Por otro lado, el arrendatario optara por un producto de ahorro a largo plazo, cuya rentabilidad variara a lo largo del tiempo en función de su aversión al riesgo, de manera que llegado el momento de la jubilación disponga de un capital.

Household consumption pattern and buying behavior for fish in an area Mymensingh, Bangladesh

The study was conducted on 238 households in Bangladesh Agricultural University campus and its adjoining areas in Mymensingh. The household were divided into four groups based on their per capita income. Monthly expenditure on fish, income elasticity of demand and marginal propensity to consume were calculated. 'Weighted average' method was used to study the level of preference for fish by sex and age groups and frequency of its purchase. The per capita monthly expenditure on fish of overall households was found to be Tk. 178.83. The consumption increased considerably between and among the income groups rising from Tk. 63.95 in the lowest income group to Tk. 249.11 in the highest income group. Based on income elasticity the proportion of income spent on fish was found to be greater than the proportion of increase in income for lower middle and upper middle income groups. However, percent expenditure decreased from 8.15 in lowest to 5.49 in the highest income group. Female members between 20 and 40yrs had the highest preference for fish in general followed by male members of above 40 yrs. Children (0 to 8 yrs), on the other band, had the least preference for fish, Sing and Magur (Catfishes) were the most preferred fish species for each age and sex group. Rui, a carp, was the single most purchased fish while the introduced exotic fishes were the least bought. Freshness was found to be the most important factor followed by the appearance and taste perception that positively affected the fish purchase.

Madlener House.

A work for violin and cello commissioned by Access Contemporary Music and the Chicago Architecture Foundation. The work explores the relationship between music and architecture, specifically that of Madlener House, Chicago, home to the Graham Foundation for the Advanced Studies in the Fine Arts. The composition premiered in October 2014 at the Graham Foundation as part of Open House Chicago 2014. It was performed by William Jason Raynovich (cello) and Maria Storm (violin).