Interaction between the aryl hydrocarbon receptor and retinoic acid pathways increases matrix metalloproteinase-1 expression in keratinocytes

Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a variety of pathological lesions in humans via activation of the aryl hydrocarbon receptor (AhR) pathway. It has become apparent that this pathway interacts with a variety of signaling pathways that are believed to be involved in mediating TCDD/AhR biological effects. Our hypothesis is that TCDD mediates these pathological lesions by directly altering the expression of genes involved in matrix deposition and remodeling and that the retinoic acid signaling pathway is involved in modulating TCDD-induced effects. Therefore, we examined the effect of TCDD and all-trans retinoic acid (atRA) on the expression of matrix metalloproteinase-1 (MMP-1, interstitial collagenase), one of the proteolytic enzymes that degrade type I collagen, in normal human keratinocytes. The data show that TCDD exposure results in increased MMP-1 expression in keratinocytes that is further enhanced by co-treatment with all-trans retinoic acid. TCDD-induced expression of MMP-1 appears to be mediated through two AP-1 elements in the proximal promoter of the MMP-1 gene. However, retinoic acid-mediated induction of keratinocyte MMP-1 is a result of both promoter activation and increased mRNA stability. These findings are the first to demonstrate TCDD-induced expression of MMP-1 and to demonstrate interactions between the TCDD/AhR and retinoic acid pathways on MMP-1 expression.     

One-trial associative odor learning in neonatal mice

Behavior genetics studies in mice demand efficient training protocols for rapid phenotypic screening. However, the capacity of neonatal mice to form and retain associative memories has been difficult to study due to their limited sensorimotor capacities. The present study describes a method for robust, naturalistic associative learning in neonatal mice as young as 3 days old. After removal of the dam from the home cage for 2 h, preweanling CD-1 mice of ages 3, 5, and 10 days postnatal were conditioned to associate an arbitrary odorant with the suckling and milk delivery that ensued upon her return to the home cage. After a second maternal deprivation, neonates were tested on their acquired preference for that odorant. Neonates exhibited a learned preference for the conditioned odorant over a novel control odorant. No learning was observed without deprivation, that is, when the dam was removed only briefly for scenting. One-trial learning sufficed to show clear preferences for the conditioned odorant, although repeated training (three sessions over 8 days) significantly increased the expression of preference. The development of neonatal associative learning protocols requiring minimal human intervention is important for the behavioral phenotyping of mutant and transgenic strains, particularly those modeling developmental disorders.     

Lactobacilli-expressed single-chain variable fragment (scFv) specific for intercellular adhesion molecule 1 (ICAM-1) blocks cell-associated HIV-1 transmission across a cervical epithelial monolayer

The vaginal and cervical epithelia provide an initial barrier to sexually acquired HIV-1 infection in women. To study the interactions between HIV-1-infected cells or cell-free HIV-1 and the reproductive epithelium, the transmission of HIV-1 by infected cells or cell-free virus across human cervical epithelial cells was examined using a Transwell culture system. Cell-associated HIV-1 was transmitted more efficiently than cell-free virus, and monocyte-associated virus was transmitted most efficiently. Abs to ICAM-1 added to the apical side of the epithelium blocked cell-mediated transepithelial HIV-1 transmission in vitro. When used in a previously described model of vaginal HIV-1 transmission in human PBL-SCID mice, anti-murine ICAM-1 Abs (0.4 microg/10 microl) also blocked vaginal transmission of cell-associated HIV-1 in vivo. To evaluate a candidate delivery system for the use of this Ab as an anti-HIV-1 microbicide, anti-ICAM single-chain variable fragment Abs secreted by transformed lactobacilli were evaluated for their protective efficacy in the Transwell model. Like the intact Ab and Fab derived from it, the single-chain variable fragment at a concentration of 6.7 microg/100 microl was able to reduce HIV-1 transmission by 70 +/- 5%. These data support the potential efficacy of an anti-ICAM Ab delivered by lactobacilli for use as an anti-HIV-1 microbicide.     

Activity following arousal in winter in North American vespertilionid bats

• 1 Many bat species hibernate to conserve energy during winter and like all hibernators they commonly arouse. During these arousals, some bats may undertake activities away from the hibernation site. Systematic ecological studies of the frequency and purpose of winter activity in temperate zone bats of North America are rare and much of the literature involves observations of single individuals or unmarked populations.
• 2 We review the available literature on winter activity among North American vespertilionid bats to highlight the paucity of data on this subject and to stimulate future research. Due to the lack of repeated, systematic studies on most North American species, the conclusions drawn are general or pertain only to parts of the geographical range of any species.
• 3 We suggest that winter activity is ubiquitous among temperate zone bats, but the degree and purpose of activity varies greatly between and within species. In general, cave‐dwelling bats tend to be relatively inactive compared with tree and foliage roosting bats during winter.
• 4 Cave‐dwelling and tree cavity‐dwelling species do not appear to feed, but they do drink and occasionally copulate during the hibernation period. Species that hibernate in foliage or leaf litter are the most active species during winter and may feed and drink throughout winter, although they probably do not copulate because of their solitary nature.
• 5 We encourage researchers to conduct studies on all aspects of winter activity for North American vespertilionids across wide latitudinal and altitudinal gradients. We suggest studies in the near future be focused on estimating the energetic costs and benefits of winter activity through determination of the frequency and intensity of winter feeding activity and more thorough examinations of movements within and among caves. Studies on common, wide‐ranging species have the potential to illuminate large‐scale patterns and differences and should be favoured over studies on rarer species.

     

Compression or tension? The stress distribution in the proximal femur

Background  

Questions regarding the distribution of stress in the proximal human femur have never been adequately resolved. Traditionally, by considering the femur in isolation, it has been believed that the effect of body weight on the projecting neck and head places the superior aspect of the neck in tension. A minority view has proposed that this region is in compression because of muscular forces pulling the femur into the pelvis. Little has been done to study stress distributions in the proximal femur. We hypothesise that under physiological loading the majority of the proximal femur is in compression and that the internal trabecular structure functions as an arch, transferring compressive stresses to the femoral shaft.     

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.     

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.