Functional neuroanatomy of the hypnotic state

The neural mechanisms underlying hypnosis and especially the modulation of pain perception by hypnosis remain obscure. Using PET we first described the distribution of regional cerebral blood flow during the hypnotic state. Hypnosis relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness". The hypnotic state was related to the activation of a widespread set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal and anterior cingulate cortices. This pattern of activation shares some similarities with mental imagery, from which it mainly differs by the relative deactivation of precuneus. Second, we looked at the anti-nociceptive effects of hypnosis. Compared to the resting state, hypnosis reduced pain perception by approximately 50%. The hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation were modulated by the activity in the midcingulate cortex (area 24a'). Finally, we assessed changes in cerebral functional connectivity related to hypnosis. Compared to normal alertness (i.e., rest and mental imagery), the hypnotic state, significantly enhanced the functional modulation between midcingulate cortex and a large neural network involved in sensory, affective, cognitive and behavioral aspects of nociception. These findings show that not only pharmacological but also psychological strategies for pain control can modulate the cerebral network involved in noxious perception.     

A study of the DNA damage checkpoint in Candida albicans: uncoupling of the functions of Rad53 in DNA repair,cell cycle regulation and genotoxic stress‐induced polarized growth

In response to genotoxic stress (GS), Candida albicans can undergo polarized growth and massive genome rearrangements including loss‐of‐heterozygosity (LOH) events. We evaluated the contribution of the CaRad53p and CaDun1p kinases of the DNA damage checkpoint (DDCP) in these processes. Characterization of C. albicans rad53ΔΔ and dun1ΔΔ mutants revealed that the two kinases were involved in the maintenance of heterozygosity. SNP‐RFLP typing and whole‐genome sequencing of rad53ΔΔ isolates having undergone a LOH revealed that, according to the chromosome on which LOH had occurred, these were predominantly due to break‐induced replication/mitotic cross‐over or chromosome loss. Loss of CaRAD53 also resulted in frequent aneuploidies. Deletion of CaDUN1 led to an increase in recombination‐dependent LOH but did not trigger aneuploidies. It also increased GS sensitivity but did not impair GS‐induced polarized growth contrary to CaRAD53 deletion. Characterization of CaRad53p site‐directed mutants demonstrated that its kinase activity and N‐terminal phosphorylation sites were crucial for its function in the resistance to GS, maintenance of heterozygosity, cell cycle regulation and polarized growth. Moreover, using phosphomimic mutants, we revealed an uncoupling of the functions of CaRad53p in these different processes, thus providing a novel understanding of how the DDCP may regulate downstream events in response to GS.     

Genetic Diversity Among Candida albicans Isolates Associated with Vertical Transmission in Preterm Triplets

We report a case of congenital candidiasis in triplets, in the context of premature labor at 25 weeks gestation, without symptomatic vaginitis or chorioamnionitis. All three infants died as a result of prematurity, aggravated by systemic candidiasis. Multi-locus sequence typing confirmed vertical transmission of Candida albicans from the mother to the triplets and revealed a slight diversity among the strains isolated from the neonates.     

Differential sensitization of cancer cells to doxorubicin by DHA: a role for lipoperoxidation

Polyunsaturated fatty acids have been reported to enhance the cytotoxic activity of several anticancer drugs. In the present study, we observed that doxorubicin chemosensitization of breast cancer cell lines by docosahexaenoic acid (DHA, a long-chain omega-3 polyunsaturated fatty acid) was cell-line selective, affecting MDA-MB-231 and MCF-7 dox (a doxorubicin-resistant cell line) but not the parental MCF-7 cell line. DHA supplementation led to an increase in membrane phospholipid DHA level, but did not induce changes in intracellular [(14)C]doxorubicin accumulation. In MDA-MB-231, doxorubicin efficacy enhancement by DHA was linked to an increase in malondialdehyde level, a final product of lipid peroxidation. DHA elicited by itself a 3.7-fold malondialdehyde level increase, additive to that induced by doxorubicin. Addition of doxorubicin to DHA further increased the glutathione level, indicative of the generation of an oxidative stress. In contrast to MDA-MB-231, doxorubicin did not increase the malondialdehyde level in MCF-7, although DHA induced lipid peroxidation. Therefore in MCF-7, lipid peroxidation induced by DHA itself was not sufficient to trigger an oxidative stress and to subsequently increase sensitivity to doxorubicin. These data indicate that the differential effect of DHA among cells on drug toxicity results from a differential oxidative response to doxorubicin. Chemosensitization through fatty acids appears as a new promising adjuvant therapeutic paradigm, since omega-3 fatty acids are physiological molecules found in food and are nontoxic in vivo.     

PPARβ mRNA expression,reduced by n − 3 PUFA diet in mammary tumor,controls breast cancer cell growth

The effect of numerous anticancer drugs on breast cancer cell lines and rodent mammary tumors can be enhanced by a treatment with long-chain n − 3 polyunsaturated fatty acids (n − 3 PUFA) such as docosahexaenoic acid (DHA, 22:6n − 3) which is a natural ligand of peroxisome proliferator-activated receptors (PPAR). In order to identify the PPAR regulating breast cancer cell growth, we tested the impact of siRNA, selected to suppress PPARα, PPARβ or PPARγ mRNA in MDA-MB-231 and MCF-7 breast cancer cell lines. The siPPARβ was the most effective to inhibit breast cancer cell growth in both cell lines. Using PPARα, PPARβ and PPARγ pharmacological antagonists, we showed that PPARβ regulated DHA-induced inhibition of growth in MDA-MB-231 and MCF-7 cells. In addition, the expressions of all 3 PPAR mRNA were co-regulated in both cell lines, upon treatments with siRNA or PPAR antagonists. PPAR mRNA expression was also examined in the NitrosoMethylUrea (NMU)-induced rat mammary tumor model. The expressions of PPARα and PPARβ mRNAs were correlated in the control group but not in the n − 3 PUFA group in which the expression of PPARβ mRNA was reduced. Although PPARα expression was also increased in the n − 3 PUFA-enriched diet group under docetaxel treatment, it is only the expression of PPARβ mRNA that correlated with the regression of mammary tumors: those that most regressed displayed the lowest PPARβ mRNA expression. Altogether, these data identify PPARβ as an important player capable of modulating other PPAR mRNA expressions, under DHA diet, for inhibiting breast cancer cell growth and mammary tumor growth.     

Comparison of E,E-Farnesol Secretion and the Clinical Characteristics of Candida albicans Bloodstream Isolates from Different Multilocus Sequence Typing Clades

Using multilocus sequence typing (MLST), Candida albicans can be subdivided into 18 different clades. Farnesol, a quorum-sensing molecule secreted by C. albicans, is thought to play an important role in the development of C. albicans biofilms and is also a virulence factor. This study evaluated whether C. albicans bloodstream infection (BSI) strains belonging to different MLST clades secrete different levels of E,E-farnesol (FOH) and whether they have different clinical characteristics. In total, 149 C. albicans BSI isolates from ten Korean hospitals belonging to clades 18 (n = 28), 4 (n = 23), 1 (n = 22), 12 (n = 17), and other clades (n = 59) were assessed. For each isolate, the FOH level in 24-hour biofilms was determined in filtered (0.45 μm) culture supernatant using high-performance liquid chromatography. Marked differences in FOH secretion from biofilms (0.10–6.99 μM) were observed among the 149 BSI isolates. Clade 18 isolates secreted significantly more FOH than did non-clade 18 isolates (mean ± SEM; 2.66 ± 0.22 vs. 1.69 ± 0.10 μM; P < 0.001). Patients with isolates belonging to clade 18 had a lower mean severity of illness than other patients, as measured using the “acute physiology and chronic health evaluation” (APACHE) III score (14.4 ± 1.1 vs. 18.0 ± 0.7; P < 0.05). This study provides evidence that C. albicans BSI isolates belonging to the most prevalent MLST clade (clade 18) in Korea are characterized by increased levels of FOH secretion and less severe illness.     

Influence des variations expérimentales de la calcémie sur la morphologie fine des cellules C du rat et du poulet

Résumé Les expériences d'hypercalcémie aigües et chroniques provoquent chez le rat des modifications spectaculaires des cellules C. Ces résultats sont en accord avec les données physiologiques sur la sécrétion de calcitonine chez le mammifère. Chez le poulet, par contre, les mêmes expériences ne provoquent pas de modifications indiscutables des Corps ultimobranchiaux (C.U.B.). Seule, l'injection intraveineuse de calcium provoque une dégranulation d'ailleurs partielle et assez peu accusée, des cellules C. L'inertie réactionnelle des C.U.B., que nous constatons morphologiquement, ressort également des données contradictoires sur le rôle physiologique de la calcitonine chez l'oiseau.

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Influence of experimental modifications of calcemia on the fine structure of the C-cells in rat and in chicken

Summary Acute and chronic hypercalcemia in rats induce spectacular modifications of the C cells. These results are in agreement with the physiological data on calcitonin secretion in mammals. The same experiments in chickens, however fail to provide a net modification of the ultimobranchial body. Only an intravenous injection of calcium induces degranulation of the C cells, and even then, this is partial and hardly evident. The lack of the ultimobranchial body response as observed in our morphological study may be compared with the conflicting physiological data on the role of calcitonin in birds.

     

Nematosomes or nucleolus-like bodies in hypothalamic neurons,the subfornical organ and adenohypophysial cells of the rat

Summary Fibrillar intracytoplasmic bodies, generally referred to as nematosomes or nucleolar like bodies (NLBs), are not only observed in various types of neurons in the hypothalamus and subfornical organ but also in the glandular cells of the pars tuberalis and the pars intermedia hypophyses. According to their cytochemical properties the NLBs are probably of ribonucleoprotein nature. Within the neurons NLBs occur within perikarya and processes. Their presence within the neurosecretory nerve fibers of the neural lobe proves their ability to migrate within the axon. Morphologic modifications of NLBs are observed in stimulated neurons and after colchicine treatment. Colchicine causes a characteristic dense texture of NLBs and a peripheral agglomeration of mitochondria very similar to the rosette arrangement observed in oocytes. Our findings suggest a structural and functional similarity of NLBs in neurons and oocytes, in which their nucleolar origin appears obvious and where they seem to represent preribosomal material. It is very likely that the axonal migration of the NLBs reflects transport of ribosomal RNA for delayed utilization (as in oocytes).This paper is dedicated to Prof. F. Stutinsky for his 65th birthday.     

Intérêt de la spectrométrie de masse de type MALDI-TOF pour l’identification des champignons filamenteux

Identification of filamentous fungi, molds and dermatophytes, is currently based on the morphological study of colonies and therefore the experience of the mycologist. These techniques are not sufficiently precise to distinguish between different species within the same section. Furthermore, identification can be delayed for several weeks due to subcultures on specific media. MALDI-TOF MS allows correct identification of filamentous fungi until the species level in more than 95% of cases in most studies. MALDI-TOF MS is a fast and precise identification technique for filamentous fungi; however most of the different databases need to be further evaluated in routine and completed to broaden the spectrum of species identified.