The role of eosinophilia in atopic diseases, including asthma, is well established, as is the well-known role of IL-5 as a major eosinophilopoeitin and chemoattractant. Following influenza A virus ...infection of mice, type 2 innate lymphoid cells are recruited to the respiratory tract and produce large quantities of IL-5, which contributes to the recruitment of eosinophils into the infected lungs during the recovery phase of infection. We demonstrate here that while IL-5 is required for optimal recovery from influenza A virus infection in BALB/c and C57BL/6 mice, the protective effect of IL-5 is independent of eosinophils, suggesting an alternative cellular target. We describe the unexpected finding of IL-5 receptor alpha (CD125) expression on neutrophils infiltrating the inflamed mouse lungs, as well as on neutrophils at other anatomic sites. We extend this finding of neutrophil CD125 expression to humans, specifically to neutrophils found in the bronchoalveolar lavage fluid from the inflamed lungs of children with treatment-refractory asthma. We further demonstrate that the IL-5 receptor on neutrophils is capable of signal transduction. Our data provide further evidence that neutrophils can play a role bridging atopic type 2 and innate anti-microbial immunity.
We investigated changes in cadherin structure at the cell surface that regulate its adhesive activity. Colo 205 cells are nonadhesive cells with a full but inactive complement of E-cadherin-catenin ...complexes at the cell surface, but they can be triggered to adhere and form monolayers. We were able to distinguish the inactive and active states of E-cadherin at the cell surface by using a special set of monoclonal antibodies (mAbs). Another set of mAbs binds E-cadherin and strongly activates adhesion. In other epithelial cell types these activating mAbs inhibit growth factor-induced down-regulation of adhesion and epithelial morphogenesis, indicating that these phenomena are also controlled by E-cadherin activity at the cell surface. Both types of mAbs recognize conformational epitopes at different interfaces between extracellular cadherin repeat domains (ECs), especially near calcium-binding sites. Activation also induces p120-catenin dephosphorylation, as well as changes in the cadherin cytoplasmic domain. Moreover, phospho-site mutations indicate that dephosphorylation of specific Ser/Thr residues in the N-terminal domain of p120-catenin mediate adhesion activation. Thus physiological regulation of the adhesive state of E-cadherin involves physical and/or conformational changes in the EC interface regions of the ectodomain at the cell surface that are mediated by catenin-associated changes across the membrane.
The sperm chromatin structure assay (SCSA) has been suggested as a predictor of fertility in vivo as well as in vitro. The available data however, have been based on limited numbers of treatments. We ...aimed to define the clinical role of SCSA in assisted reproduction. METHODS: A total of 998 cycles 387 intrauterine insemination (IUI), 388 IVF and 223 ICSI from 637 couples were included. SCSA results were expressed as DNA fragmentation index (DFI) and high DNA stainable (HDS) cell fractions. Outcome parameters were biochemical pregnancy (BP), clinical pregnancy (CP) and delivery (D). RESULTS: For IUI, the odds ratios (ORs) for BP, CP and D were significantly lower for couples with DFI >30% as compared with those with DFI ≤30%. No statistical difference between the outcomes of ICSI versus IVF in the group with DFI ≤30% was seen. In the DFI >30% group, the results of ICSI were significantly better than those of IVF. CONCLUSIONS: DFI can be used as an independent predictor of fertility in couples undergoing IUI. As a result, we propose that all infertile men should be tested with SCSA as a supplement to the standard semen analysis. When DFI exceeds 30%, ICSI should be the method of choice.
Background and purpose: Animal and human studies have shown that sex and hormones are key factors in modulating addiction. Previously, we have demonstrated that self‐administration of the ...cannabinoid CB1 receptor agonist WIN55,212‐2 (WIN; 12.5 µg·kg−1 per infusion) is dependent on sex, intact female rats being more sensitive than males to the reinforcing properties of cannabinoids, and on the oestrous cycle, ovariectomized (OVX) females being less responsive than intact females.
Experimental approach: This follow‐up study investigated whether sex and ovarian function also affect reinstatement of cannabinoid‐seeking in rats after exposure to drug or cue priming.
Key results: After priming with 0.15 or 0.3 mg·kg−1 WIN, intact female rats exhibited stronger reinstatement than males and OVX females. Responses of intact female rats were higher than those of male and OVX rats even after priming with a drug‐associated visual (Light) or auditory (Tone) cue, or a WIN + Light combination. However, latency to the first response did not differ between intact and OVX female rats, and males showed the longest latency to initiate lever‐pressing activity.
Conclusions and implications: Our study provides compelling evidence for a pivotal role of sex and the oestrous cycle in modulating cannabinoid‐seeking, with ovariectomy diminishing drug and cue‐induced reinstatement. However, it is possible that sex differences during self‐administration training are responsible for sex differences in reinstatement. Finding that not only drug primings but also acute exposure to drug‐associated cues can reinstate responding in rats could have significant implications for the development of pharmacological and behavioural treatments of abstinent female and male marijuana smokers.
This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
The results obtained from a study of the mass distribution of 36 spiral galaxies are presented. The galaxies were observed using Fabry–Perot interferometry as part of the GHASP survey. The main aim ...of obtaining high-resolution Hα 2D velocity fields is to define more accurately the rising part of the rotation curves which should allow to better constrain the parameters of the mass distribution. The Hα velocities were combined with low resolution H i data from the literature, when available. Combining the kinematical data with photometric data, mass models were derived from these rotation curves using two different functional forms for the halo: an isothermal sphere (ISO) and a Navarro–Frenk–White (NFW) profile. For the galaxies already modelled by other authors, the results tend to agree. Our results point at the existence of a constant density core in the centre of the dark matter haloes rather than a cuspy core, whatever the type of the galaxy from Sab to Im. This extends to all types the result already obtained by other authors studying dwarf and low surface brightness galaxies but would necessitate a larger sample of galaxies to conclude more strongly. Whatever model is used (ISO or NFW), small core radius haloes have higher central densities, again for all morphological types. We confirm different halo scaling laws, such as the correlations between the core radius and the central density of the halo with the absolute magnitude of a galaxy: low-luminosity galaxies have small core radius and high central density. We find that the product of the central density with the core radius of the dark matter halo is nearly constant, whatever the model and whatever the absolute magnitude of the galaxy. This suggests that the halo surface density is independent from the galaxy type.
Background and purpose:
We recently demonstrated the existence of strain differences in self‐administration of the cannabinoid CB1 receptor agonist WIN55,212‐2 (WIN) by Long Evans (LE) and Lister ...Hooded (LH) but not Sprague‐Dawley (SD) male rats. This follow‐up study is aimed at verifying whether sex and ovarian hormones might also be critical factors in the initiation, retention and extinction of WIN self‐administration.
Experimental approach:
LE, LH and SD male and female rats, the latter either intact or bilaterally ovariectomized (OVX), were trained to self‐administer WIN (12.5 μg kg−1 per infusion) under a FR1 reinforcement schedule, using lever‐pressing.
Key results:
Data showed that contrary to the findings in SD rats, LE and LH rats developed robust cannabinoid intake, with rates of responding for WIN being constantly higher in intact females than in males (+45 and +42% for LE and LH strains, respectively). In comparison with intact females, OVX females of both strains acquired self‐administration at lower rates, displaying slower acquisition, lower drug intake (−42 and −52% for LE and LH, respectively) and longer extinction.
Conclusions and implications:
These findings provide the first evidence of significant sex differences in cannabinoid self‐administration, females acquiring stable WIN intake at higher rates and more rapidly than males. Moreover, when compared to intact females, a lower percentage of LE and LH OVX rats acquired and maintained stable drug intake, suggesting that ovarian hormones might represent a critical factor in modulating the reinforcing effect of cannabinoids.
British Journal of Pharmacology (2007) 152, 795–804; doi:10.1038/sj.bjp.0707465; published online 24 September 2007
BACKGROUND
Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male ...semen quality.
METHODS
PFCs were measured in serum from 588 partners of pregnant women from Greenland, Poland and Ukraine who provided a semen sample, using liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) could be detected in >97% of the samples. The associations between levels of these compounds and semen volume, sperm concentration, total sperm count, motility and morphology were assessed.
RESULTS
Across countries, sperm concentration, total sperm count and semen volume were not consistently associated with PFOS, PFOA, PFHxS or PFNA levels. The proportion of morphologically normal cells was 35% lower 95% confidence interval (CI): 4–66%) for the third tertile of PFOS exposure as compared with the first. A similar reduction was found in relation to increasing PFHxS levels. At the third PFOA exposure tertile, the percentage of motile spermatozoa was 19% (95% CI: 1 to 39%) higher than in the first.
CONCLUSIONS
The most robust finding in the present study was the negative associations between PFOS exposure and sperm morphology suggesting adverse effects of PFOS on semen quality, possibly due to interference with the endocrine activity or sperm membrane function. It cannot be excluded that this association and the positive association between PFOA and semen motility, which was not consistent across countries, might represent a chance finding due to the multiple statistical tests being performed.
Background Prenatal cannabis exposure has been linked to addiction vulnerability, but the neurobiology underlying this risk is unknown. Methods Striatal dopamine and opioid-related genes were studied ...in human fetal subjects exposed to cannabis (as well as cigarettes and alcohol). Cannabis-related gene disturbances observed in the human fetus were subsequently characterized with an animal model of prenatal Δ-9-tetrahydrocannabinol (THC) (.15 mg/kg) exposure. Results Prenatal cannabis exposure decreased dopamine receptor D2 ( DRD2 ) messenger RNA expression in the human ventral striatum (nucleus accumbens NAc), a key brain reward region. No significant alterations were observed for the other genes in cannabis-exposed subjects. Maternal cigarette use was associated with reduced NAc prodynorphin messenger RNA expression, and alcohol exposure induced broad alterations primarily in the dorsal striatum of most genes. To explore the mechanisms underlying the cannabis-associated disturbances, we exposed pregnant rats to THC and examined the epigenetic regulation of the NAc Drd2 gene in their offspring at postnatal day 2, comparable to the human fetal period studied, and in adulthood. Chromatin immunoprecipitation of the adult NAc revealed increased 2meH3K9 repressive mark and decreased 3meH3K4 and RNA polymerase II at the Drd2 gene locus in the THC-exposed offspring. Decreased Drd2 expression was accompanied by reduced dopamine D2 receptor (D2 R) binding sites and increased sensitivity to opiate reward in adulthood. Conclusions These data suggest that maternal cannabis use alters developmental regulation of mesolimbic D2 R in offspring through epigenetic mechanisms that regulate histone lysine methylation, and the ensuing reduction of D2 R might contribute to addiction vulnerability later in life.
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