Effects of progesterone or estradiol on uterine tubal transport of ova in the cow

An experiment was designed to determine the effect of progesterone (P) or estradiol benzoate (EB) on uterine tubal transport of ova in the cow. Intramuscular injections of P, EB, or corn oil (C) were administered to heifers 24 hours after the end of estrus. The heifers were euthanatized 60 hours after the end of estrus and the location of the ovum or zygote was determined. Venous serum levels of progesterone and estradiol-17beta were measured by radioimmunoassay. The mean uterine tube (UT) length was 23.9 cm. An ovum or zygote was recovered from 11 of 14 heifers. Serum levels of progesterone and estradiol-17beta were above normal bovine levels following the P and EB treatments, respectively. The mean UT ovum transport rates were 0.42, 0.21 and 0.23 cm/hour in the P, EB and C treatment groups, respectively. The UT ovum transport rate was increased (P<0.05) by the P treatment and EB treatment had no effect (P > 0.05) when compared with the C treatment.     

Seasonality of planktonic ciliated protozoa in 20 subtropical Florida lakes of varying trophic state

The planktonic ciliate populations of 20 Florida lakes ranging from oligotrophic to hypereutrophic were examined monthly for one year. Oligotrophic lakes displayed abundance peaks during fall mixis and biomass peaks in late winter and fall. Mesotrophic systems exhibited a spring-fall bimodality in ciliate abundance with a biomass maxima occurring during fall. Eutrophic/hypereutrophic lakes had pronounced abundance and biomass maxima during summer, with the large ciliates Plagiopyla nasuta and Paramecium trichium often contributing heavily to the midsummer biomass peak. Members of the Oligotrichida numerically dominated abundance and biomass peaks in oligotrophic lakes while the Scuticociliatida dominated the communities of higher trophic states. Total ciliate abundance and biomass were strongly correlated with chlorophyll a concentrations as were various ciliate taxonomic groups. The relationship between ciliate seasonal distribution in these subtropical lakes with lake thermal regimes and trophic state is discussed.     

Interpretation of bryozoan microfossils in lacustrine sediment cores

Bryozoan statoblasts were isolated from the surficial sediments of 30 Florida lakes representing a gradient of trophic conditions. A prerequisite for lake selection was a good data base for water chemistry that was collected within the past 5–10 years. A novel technique of employing 210-Pb as a dilution tracer was used to estimate sedimentation rates for each lake. The net annual accumulation rate for bryozoan statoblasts was calculated for each lake and correlated with twelve physical, chemical, and biological variables. The results suggest that bryozoan distributions are strongly controlled by the extent of the littoral zone and phytoplankton biomass. It appears that bryozoan abundance in excessively weeded lakes may be limited by phytoplankton in spite of the richly developed habitat. Separation of the importance of food requirements from habitat requirements was not possible from this initial survey.     

"Plate cherry picking": a novel semi-sequential screening paradigm for cheaper, faster, information-rich compound selection

This work describes a novel semi-sequential technique for in silico enhancement of high-throughput screening (HTS) experiments now employed at Novartis. It is used in situations in which the size of the screen is limited by the readout (e.g., high-content screens) or the amount of reagents or tools (proteins or cells) available. By performing computational chemical diversity selection on a per plate basis (instead of a per compound basis), 25% of the 1,000,000-compound screening was optimized for general initial HTS. Statistical models are then generated from target-specific primary results (percentage inhibition data) to drive the cherry picking and testing from the entire collection. Using retrospective analysis of 11 HTS campaigns, the authors show that this method would have captured on average two thirds of the active compounds (IC(50) < 10 microM) and three fourths of the active Murcko scaffolds while decreasing screening expenditure by nearly 75%. This result is true for a wide variety of targets, including G-protein-coupled receptors, chemokine receptors, kinases, metalloproteinases, pathway screens, and protein-protein interactions. Unlike time-consuming "classic" sequential approaches that require multiple iterations of cherry picking, testing, and building statistical models, here individual compounds are cherry picked just once, based directly on primary screening data. Strikingly, the authors demonstrate that models built from primary data are as robust as models built from IC(50) data. This is true for all HTS campaigns analyzed, which represent a wide variety of target classes and assay types.     

Identification of amino acids involved in the binding of hMIP-1α to CC-CKR1, a MIP-lα receptor found on neutrophils

Human macrophage inflammatory protein-1 (hMIP-1) and human macrophage inflammatory protein-1 (hMIP-1) are chemokines involved in a diverse range of immunological effects. Both hMIP-1 and hMIP-1 are involved in the activation of monocytes and THP-1 cells probably through a common receptor(s). However, only hMIP-1 can bind to neutrophils with high affinity, presumably through CC-CKR1 (CKR1). Since the structure of these two proteins is highly conserved, non-conserved amino acids must define the disparate binding patterns that these two proteins exhibit. Measurements of binding, chemotaxis and calcium influx conducted with hMIP-1 and hMIP-1 chimeric proteins and mutants show that two amino acids (37K and 43L) are important in the binding and signaling of hMIP-1 through CKR1. Furthermore, we also show that mutations of the three charged amino acids at the C-terminus of hMIP-1 and hMIP-1 (amino acids 61, 65 and 67), do not adversely affect the binding to THP-1 cells.