Responsiveness of nigral neurons to the stimulation of striatal dopaminergic receptors in the rat

The microinfusion of low doses of apomorphine into the striatum of anesthetized rats depressed the electrical activity of the neurons of the substantia nigra pars compacta while the infusion of bromocriptine had an excitatory or inhibitory effect. These data suggest that:1) the action of the two dopamine agonists on the striato-nigral pathway is different; 2) the striatum might contain dopaminergic receptors located on cells projecting to the substantia nigra with different roles in the feedback regulation of the latter; 3) the inhibitory action of systemically injected apomorphine is not simply due to a stimulation of dopamine “autoreceptors” but also to an action mediated by fibers descending from the striatum to the substantia nigra.     

The "Goldilocks Effect" in Cystic Fibrosis: identification of a lung phenotype in the <Emphasis Type="Italic">cftr</Emphasis> knockout and heterozygous mouse

Background  

Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype.     

Ryanodine receptors, a family of intracellular calcium ion channels, are expressed throughout early vertebrate development

Background

We developed a new version of the open source software package Peptrix that can yet compare large numbers of Orbitrap? LC-MS data. The peptide profiling results for Peptrix on MS1 spectra were compared with those obtained from a small selection of open source and commercial software packages: msInspect, Sieve? and Progenesis?. The properties compared in these packages were speed, total number of detected masses, redundancy of masses, reproducibility in numbers and CV of intensity, overlap of masses, and differences in peptide peak intensities. Reproducibility measurements were taken for the different MS1 software applications by measuring in triplicate a complex peptide mixture of immunoglobulin on the Orbitrap? mass spectrometer. Values of peptide masses detected from the high intensity peaks of the MS1 spectra by peptide profiling were verified with values of the MS2 fragmented and sequenced masses that resulted in protein identifications with a significant score.

Findings

Peptrix finds about the same number of peptide features as the other packages, but peptide masses are in some cases approximately 5 to 10 times less redundant present in the peptide profile matrix. The Peptrix profile matrix displays the largest overlap when comparing the number of masses in a pair between two software applications. The overlap of peptide masses between software packages of low intensity peaks in the spectra is remarkably low with about 50% of the detected masses in the individual packages. Peptrix does not differ from the other packages in detecting 96% of the masses that relate to highly abundant sequenced proteins. MS1 peak intensities vary between the applications in a non linear way as they are not processed using the same method.

Conclusions

Peptrix is capable of peptide profiling using Orbitrap? files and finding differential expressed peptides in body fluid and tissue samples. The number of peptide masses detected in Orbitrap? files can be increased by using more MS1 peptide profiling applications, including Peptrix, since it appears from the comparison of Peptrix with the other applications that all software packages have likely a high false negative rate of low intensity peptide peaks (missing peptides).     

Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis

Background

Canine hemangiosarcoma (HSA) is a malignant tumor with poor long-term prognosis due to development of metastasis despite aggressive treatment. The phosphatidyl-inositol-3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is involved in its endothelial pathologies; however, it remains unknown how this pathway plays a role in canine HSA. Here, we characterized new canine HSA cell lines derived from nude mice-xenografted canine HSAs and investigated the deregulation of the signaling pathways in these cell lines.

Results

Seven canine HSA cell lines were established from 3 xenograft canine HSAs and showed characteristics of endothelial cells (ECs), that is, uptake of acetylated low-density lipoprotein and expression of canine-specific CD31 mRNA. They showed varied morphologies and mRNA expression levels for VEGF-A, bFGF, HGF, IGF-I, EGF, PDGF-B, and their receptors. Cell proliferation was stimulated by these growth factors and fetal bovine serum (FBS) in 1 cell line and by FBS alone in 3 cell lines. However, cell proliferation was not stimulated by growth factors and FBS in the remaining 3 cell lines. Phosphorylated p44/42 Erk1/2 was increased by FBS stimulation in 4 cell lines. In contrast, phosphorylation of Akt at Ser⁴⁷³, mTOR complex 1 (mTORC1) at Ser²⁴⁴⁸, and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) at Ser⁶⁵ was high in serum-starved condition and not altered by FBS stimulation in 6 cell lines, despite increased phosphorylation of these residues in normal canine ECs. This suggested that the mTORC2/Akt/4E-BP1 pathway was constitutively activated in these 6 canine HSA cell lines. After cell inoculation into nude mice, canine HSA tumors were formed from 4 cell lines and showed Akt and 4E-BP1 phosphorylation identical to the parental cell lines.

Conclusions

Our findings suggest that the present cell lines may be useful tools for investigating the role of the mTORC2/Akt/4E-BP1 pathway in canine HSA formation both in vivo and in vitro.     

A multiple approach for the evaluation of the spatial distribution and dynamics of a forest habitat: the case of Apennine beech forests with Taxus baccata and Ilex aquifolium

An approach integrating phytosociological and stand structure surveys with the predictive modelling of species distribution was applied to analyse the spatial distribution and dynamics of the Apennine beech forests with Taxus and Ilex, a high conservation priority forest habitat in Europe. The homogeneity of the habitat was tested trough a Mann–Whitney test between beech woods with Taxus and those with Ilex with respect to climatic, topographic, structural and environmental parameters: the former have proven to be more microthermic, mesophilous and characterised by a closer canopy. Five statistical models were compared to analyse the relationship between bioclimatic parameters and Taxus and Ilex spatial distribution: Regression Tree Analysis, the most efficient model, has shown that the distribution of Taxus is influenced by precipitation variables, while Ilex is mainly influenced by temperature variables. This model highlighted that Ilex has a potential area that surrounds, at lower altitudes, that of Taxus. A stepwise multiple regression analysis has been applied to identify the factors influencing the regeneration of the two species: beside climatic parameters, Taxus regeneration is negatively influenced by soil nitrate concentration (an indicator of livestock disturbance) while Ilex is negatively influenced by beech forest cover. Traditional management practices seem to have an effect on the regeneration of the two species: frequent cuts favour the regeneration of Ilex, reducing the forest cover and allowing more light penetration, while Taxus, less resistant to grazing livestock, is confined to more inaccessible places. The multiple approach has proven to be useful for the elaboration of two differentiated conservation strategies for the two beech forest types.     

Automated genome mining for natural products

Background  

Discovery of new medicinal agents from natural sources has largely been an adventitious process based on screening of plant and microbial extracts combined with bioassay-guided identification and natural product structure elucidation. Increasingly rapid and more cost-effective genome sequencing technologies coupled with advanced computational power have converged to transform this trend toward a more rational and predictive pursuit.     

Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD

Background

Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age.

Methods

All participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis.

Results

Young susceptible individuals showed significantly higher increases in the expression of FcγRII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients.

Conclusions

We show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD.

Trial registration

Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00807469","term_id":"NCT00807469"}}NCT00807469

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0121-2) contains supplementary material, which is available to authorized users.