A theoretical entropy score as a single value to express inhibitor selectivity

Background  

Designing maximally selective ligands that act on individual targets is the dominant paradigm in drug discovery. Poor selectivity can underlie toxicity and side effects in the clinic, and for this reason compound selectivity is increasingly monitored from very early on in the drug discovery process. To make sense of large amounts of profiling data, and to determine when a compound is sufficiently selective, there is a need for a proper quantitative measure of selectivity.     

Methyl Jasmonate Increases the Tropane Alkaloid Scopolamine and Reduces Natural Herbivory in Brugmansia suaveolens: Is Scopolamine Responsible for Plant Resistance?

The tropane alkaloid (TA) scopolamine is suggested to protect Brugmansia suaveolens (Solanaceae) against herbivorous insects. To test this prediction in a natural environment, scopolamine was induced by methyl jasmonate (MJ) in potted plants which were left 10?days in the field. MJ-treated plants increased their scopolamine concentration in leaves and herbivory decreased. These findings suggest a cause?Ceffect relationship. However, experiments in laboratory showed that scopolamine affect differently the performance of the specialist larvae of the ithomiine butterfly Placidina euryanassa (C. Felder & R. Felder) and the generalist fall armyworm Spodoptera frugiperda (J. E. Smith): the specialist that sequester this TA from B. suaveolens leaves was not negatively affected, but the generalist was. Therefore, scopolamine probably acts only against insects that are not adapted to TAs. Other compounds that are MJ elicited may also play a role in plant resistance against herbivory by generalist and specialist insects, and deserve future investigations.     

Elevated levels of fibrinogen-derived endogenous citrullinated peptides in synovial fluid of rheumatoid arthritis patients

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints and the presence of autoantibodies directed against proteins containing the non-standard arginine-derived amino acid citrulline. The protein fibrinogen, which has an essential role in blood clotting, is one of the most prominent citrullinated autoantigens in RA, particularly because it can be found in the inflamed tissue of affected joints. Here, we set out to analyze the presence of citrullinated endogenous peptides in the synovial fluid of RA and arthritic control patients.

Methods

Endogenous peptides were isolated from the synovial fluid of RA patients and controls by filtration and solid phase extraction. The peptides were identified and quantified using high-resolution liquid chromatography-mass spectrometry.

Results

Our data reveal that the synovial fluid of RA patients contains soluble endogenous peptides, derived from fibrinogen, containing significant amounts of citrulline residues and, in some cases, also phosphorylated serine. Several citrullinated peptides are found to be more abundantly present in the synovial fluid of RA patients compared to patients suffering from other inflammatory diseases affecting the joints.

Conclusions

The increased presence of citrullinated peptides in RA patients points toward a possible specific role of these peptides in the immune response at the basis of the recognition of citrullinated peptides and proteins by RA patient autoantibodies.     

Northern Goshawk Habitat: an Intersection of Science,Management, and Conservation

Abstract: We responded to the claim by Greenwald et al. (2005) that the management recommendations for the northern goshawk in the Southwestern United States (MRNG; Reynolds et al. 1992), a food web-based conservation plan that incorporated both northern goshawk (Accipiter gentilis) and multiple prey habitats, may be inadequate to protect goshawks. Greenwald et al. (2005) based this claim on their review of 12 telemetry studies of goshawk habitat selection and 5 nontelemetry studies of the effects of vegetation structure at the home range scale on goshawk nest occupancy and reproduction that appeared after the 1992 publication of the MRNG. Greenwald et al. (2005) summarized their review as showing that 1) goshawks were habitat specialists limited to forests with mature and old-growth structures including large trees, high canopy cover, multiple canopy layering, and abundant woody debris; 2) habitats were not selected on the basis of prey abundance and, therefore, managing for prey habitats diluted goshawk habitats; and 3) selection for openings, edges, and habitat diversity was inconclusive. Our review found that when the studies' respective authors pooled their radiotagged goshawks there were weak to strong selections for old forest structures. However, the studies also documented extensive variation in use of vegetation types and structures by individual goshawks; some avoided openings, edges, young forests, and old forests, whereas others selected for these characteristics. Additionally, by virtue of their wide geographic distribution, the studies showed that the focal populations themselves occurred in a variety of forest types, some with large structural differences. We found no evidence in Greenwald's et al. (2005) review that the MRNG are inadequate to protect goshawks. Rather, the studies reviewed by Greenwald et al. (2005), as well as many studies they missed, supported the MRNG. The suggestion of inadequacy by Greenwald et al. (2005) appeared rooted in misunderstandings of goshawk habitats described in the MRNG, a discounting of the extent of variation in vegetation structural and seral stages used by goshawks, a limited understanding of the extent to which prey limits goshawks, a failure to recognize the dynamic nature of forests, and an incomplete review of the literature. We believe the MRNG are adequate because they maximize the sustainable amount of mature and old forests in goshawk home ranges and specify the kinds and intermixtures of prey habitats within home ranges. Implementation of MRNG should reduce the likelihood that the availability of vegetation structures suited to goshawk nesting and foraging, as well as abundance and availability of prey, will limit goshawk nest occupancy and reproduction.     

Twelve polymorphic microsatellite loci from the Asian citrus psyllid,Diaphorina citri Kuwayama,the vector for citrus greening disease,huanglongbing

Twelve polymorphic microsatellite markers were developed from microsatellite‐enriched DNA libraries and mined from an expressed sequence tags library of Diaphorina citri, the vector of the citrus greening disease (huanglongbing). Analysis of 288 individuals from Florida, Texas, and Brazil showed that allelic diversity ranged from three to eight alleles per locus and observed and expected heterozygosities ranged from 0.014 to 0.569 and from 0.052 to 0.653, respectively. These variable microsatellite loci can provide means for assessing overall genetic variation and migration patterns for this agriculturally important pest species. This information can be used to aid in developing successful management strategies.     

Saurian Malarial Parasites in Eastern Panama

SYNOPSIS Plasmodium gonatodi sp. nov. is described from Gonatodes albogularis fuscus of eastern Panama. It is characterized by elongate gametocytes and polymorphic schizonts containing 12-46 nuclei when apparently mature. Both proerythrocytes and erythrocytes are commonly parasitized, host cells are hypertrophied and distorted, and their nuclei are displaced. Prematuration sexual stages may be irregularly shaped and larger than mature gametocytes.
Plasmodium diploglossi Aragão and Neiva , 1909 is reported from Mabuya mabouya in eastern Panama, and Plasmodium morulum sp. nov. is described from this host. P. morulum usually parasitizes immature erythrocytes, and is characterized by lenticular or oval to round gametocytes, and schizonts with 14-40 nuclei usually arranged in a globular mass. Host cells are slightly hypertrophied and distorted, and their nuclei are usually displaced. Inoculation of infected blood into clean hosts produces numerous schizonts in white cells as well as in the erythrocyte series.
Pigment in both P. gonatodi and P. morulum , if present, consists of a few minute dark dots which do not meet the polarized light test for hemozoin.