Scanning electron and light microscopic study of microbial succession on bethlehem st. Nectaire cheese

St. Nectaire cheese is a semisoft cheese of French origin that, along with Brie and Camembert cheeses, belongs to the class of surface mold-ripened cheese. The surface microorganisms that develop on the cheese rind during ripening impart a distinctive aroma and flavor to this class of cheese. We have documented the sequential appearance of microorganisms on the cheese rind and in the curd over a 60-day ripening period. Scanning electron microscopy was used to visualize the development of surface fungi and bacteria. Light microscopy of stained paraffin sections was used to study cross sections through the rind. We also monitored the development of bacterial and yeast populations in and the pH of the curd and rind. The earliest stage of ripening (0 to 2 days) is dominated by the lactic acid bacterium Streptococcus cremoris and multilateral budding yeasts, primarily Debaryomyces and Torulopsis species. Geotrichum candidum follows closely, and then zygomycetes of the genus Mucor develop at day 4 of ripening. At day 20, the deuteromycete Trichothecium roseum appears. From day 20 until the end of the ripening process, coryneforms of the genera Brevibacterium and Arthrobacter can be seen near the surface of the cheese rind among fungal hyphae and yeast cells.     

Regulation of heptaspanning-membrane-receptor function by dimerization and clustering

G-protein-coupled receptors form homomers and heteromers; agonist-induced conformational changes within interacting receptors of the oligomer modify their pharmacology, signalling and/or trafficking. When these receptors are activated, the oligomers rearrange and cluster and a novel mechanism of receptor-operation regulation by oligomer intercommunication is possible. This intercommunication would be assisted by components of the plasma membrane and by scaffolding proteins. Receptor cross-sensitization, cross-desensitization and novel, integrated receptor responses can then develop between oligomeric receptor complexes of the cluster without direct contact between them. This concept gives a new perspective to the understanding of neurotransmission and neuronal plasticity.     

Interpopulation relationship by isonymy: application to ethnosocial groups and illegitimacy

The application of the isonymic method to establish interpopulation relationships is made difficult by such factors as: (1) a small population size; (2) the subdivision of the population into ethnosocial groups; and (3) the existence of individuals born extramaritally. The present study analyzes the validity of the isonymy method in populations where such difficulties exist. Lasker's R(ij) relationship coefficients were calculated in base to marital records from six Pocho parishes (Argentina) for the period 1766 to 1840. Three endogamous ethnosocial groups were considered-Spanish, American Indians, "Mestizos"--and a fourth group combining mates of the three previous groups. For each ethnosocial category, and taking into account paternal surnames, maternal surnames (both for legitimate and illegitimate mates), and whole surnames merged, R(i) interparish relationship matrices were obtained. All these matrices were correlated by means of the Mantel test. Maternal surnames of illegitimate mates show a similar pattern to the maternal surnames of legitimate mates and to all surnames of each category. Groups with larger sample size in every parish intercorrelate regardless of ethnosocial category. Results suggest the convenience of maximizing the sample size and using maternal surnames in populations with high illegitimacy.     

Chronic L‐DOPA induces hyperactivity,normalization of gait and dyskinetic behavior in MitoPark mice

Dopamine (DA) replacement therapy continues to be the gold standard treatment for Parkinson's disease (PD), as it improves key motor symptoms including bradykinesia and gait disturbances. With time, treatment induces side effects in the majority of patients, known as L‐DOPA‐induced dyskinesia (LID), which are often studied in animals by the use of unilateral, toxin‐induced rodent models. In this study, we used the progressive, genetic PD model MitoPark to specifically evaluate bilateral changes in motor behavior following long‐term L‐DOPA treatment at three different stages of striatal DA depletion. Besides locomotor activity, we assessed changes in gait with two automated gait analysis systems and the development of dyskinetic behavior. Long‐term treatment with a moderate, clinically relevant dose of L‐DOPA (8 mg/kg) gradually produced age‐dependent hyperactivity in MitoPark mice. In voluntary and forced gait analyses, we show that MitoPark mice with severe DA depletion have distinct gait characteristics, which are normalized to control levels following long‐term L‐DOPA treatment. The cylinder test showed an age‐dependent and gradual development of bilateral LID. Significant increase in striatal FosB and prodynorphin expression was found to accompany the behavior changes. Taken together, we report that MitoPark mice model both behavioral and biochemical characteristics of long‐term L‐DOPA treatment in PD patients and provide a novel, consistent and progressive animal model of dyskinesia to aid in the discovery and evaluation of better treatment options to counteract LID.     

Persistent facial pain increases superoxide anion production in the spinal trigeminal nucleus

Previous studies have demonstrated that there is an increase in oxidative stress in the cerebral cortex of rats after repeated painful stimulation and that long-lasting pain increases the production of superoxide ion (O₂ ^?), nitric oxide and peroxynitrite due to the activation of AMPA and NMDA receptors. The purpose of the present study was to evaluate the possible role of O₂ ^? in the transmission of oro-facial pain. Formaldehyde 1% was injected subcutaneously into one vibrissal pad of adult male Sprague-Dawley rats as a model of persistent pain, then O₂ ^? production and superoxide dismutase (SOD) activity were evaluated in the left and right spinal trigeminal nuclei. O₂ ^? production was revealed using dihidroetidium (DHE) injected at 10 or 45 min after the formalin injection in conscious or anaesthetized rats. A histochemical assay for SOD was performed to evaluate the activity of SOD at 10 min after the formalin injection. The results showed a significant increase in O₂ ^? production in the homolateral nucleus at 45 min. However, there was no significant difference between the two sides at 10 min after the formalin injection. No significant difference was observed in SOD activity between the two sides of the spinal trigeminal nucleus. This study demonstrated that there is an increased production of O₂ ^? in the second phase but not in the first phase of the formalin test; thus O₂ ^? is involved in pain induced by inflammation, but not in acute pain.     

Dopamine D2 and 5-hydroxytryptamine 5-HT(₂A) receptors assemble into functionally interacting heteromers

In view of the co-distribution of dopamine D_2LR and 5-hydroxytryptamine 5-HT_2A receptors (D_2LR and 5-HT_2AR, respectively) within inter alia regions of the dorsal and ventral striatum and their role as a target of antipsychotic drugs; in this study we assessed the potential existence of D_2LR-5-HT_2AR heteromers in living cells and the functional consequences of this interaction. Thus, by means of a proximity-based bioluminescence resonance energy transfer (BRET) approach we demonstrated that the D_2LR and the 5-HT_2AR form stable and specific heteromers when expressed in HEK293T mammalian cells. Furthermore, when the D_2LR-5-HT_2AR heteromeric signaling was analyzed we found that the 5-HT_2AR-mediated phospholipase C (PLC) activation was synergistically enhanced by the concomitant activation of the D_2LR as shown in a NFAT-luciferase reporter gene assay and a specific and significant rise of the intracellular calcium levels were observed when both receptors were simultaneously activated. Conversely, when the D_2LR-mediated adenylyl cyclase (AC) inhibition was assayed we showed that costimulation of D_2LR and 5-HT_2AR within the heteromer led to inhibition of the D_2LR functioning, thus suggesting the existence of a 5-HT_2AR-mediated D_2LR trans-inhibition phenomenon. Finally, a bioinformatics study reveals that the triplet amino acid homologies LLT (Leu-Leu-Thr) and AIS (Ala-Ile-Ser) in TM1 and TM3, respectively of the D₂R-5-HT_2AR may be involved in the receptor interface. Overall, the presence of the D_2LR-5-HT_2AR heteromer in discrete brain regions is postulated based on the existence of D_2LR-5-HT_2A receptor-receptor interactions in living cells and their codistribution inter alia in striatal regions. Possible novel therapeutic strategies for treatment of schizophrenia should be explored by targeting this heteromer.     

Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption

We report the first genome-wide association study of habitual caffeine intake. We included 47,341 individuals of European descent based on five population-based studies within the United States. In a meta-analysis adjusted for age, sex, smoking, and eigenvectors of population variation, two loci achieved genome-wide significance: 7p21 (P = 2.4 × 10(-19)), near AHR, and 15q24 (P = 5.2 × 10(-14)), between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2.     

Mitochondrial DNA haplogroups in Amerindian populations from the Gran Chaco.

Mitochondrial DNA from 141 individuals was typed for diagnostic restriction sites and the 9-bp region V deletion to examine the distribution of the founding mtDNA lineage haplotypes in three Amerindian populations (Mataco, Toba, and Pilagá) who currently inhabit the Argentinian part of the Gran Chaco. All four lineages were identified in the three tribes and four population samples studied. Disregarding ethnic or geographic origin, haplogroups B and D exhibit high incidence among the Gran Chaco inhabitants, whereas haplogroups A and C are present in a lower frequency. Three individuals possess none of the characteristic markers and, therefore, could not be assigned to one of those lineages. A neighbor-joining representation of F(ST) distances reflects the current geographic location of the populations, and this also corresponds to their historic distribution. After separating South America into four major regions (Tropical Forest, Andes, Gran Chaco, and Patagonia-Tierra del Fuego), the Gran Chaco populations present the highest average intragroup variability (Hs = 0.64) as well as the lowest intergroup diversity (G(')(ST) = 0.06). These findings suggest high levels of gene flow among the Chaco tribes, as well as with neighbor populations from outside the region.     

Plasma glutamine decreases immediately after surgery and is related to incisiveness

Glutamine (gln) is the most abundant free amino acid in the blood. It is involved in important metabolic and biochemical processes, like cell proliferation and oxidative stress. Previous studies have demonstrated that gln concentration in human plasma decreases in several conditions such as sepsis, ischemia-reperfusion, trauma, major surgery and burn. The aim of the present work was to compare the acute effects of different types of surgical interventions and of anesthetization on blood gln concentration. Plasma samples from 88 subjects (30 males and 58 females) were collected before and after major or minor surgery and the gln concentration was analyzed with high-performance liquid chromatography. The results showed that plasma gln concentration after surgery was lower than pre-surgery values and that in major surgery the decrease of gln was higher than in minor surgery. No significant effect was shown for sex or type of anesthesia. These results demonstrate the importance of a gln supplementation before a surgical intervention and show that the amount of gln supplementation should also be adjusted based on the type of surgery.