Central nervous system and hibernation

Conclusions The role of the nervous system in the mechanism of hibernation is extremely important. The special properties of the brain of hibernators permits them wonderfully to resist to hypoxia and hypothermia, such as this state ofneural hibernation, a reversible hypothermia whichBullard, David andNichols ⁶⁰ have obtained in the thirteen-lined ground squirrel (Citellus tridecimlineatus) by hypoxia at a low temperature.The study of the glycolysis of the brain of hibernators has revealed that the brain of hibernators (European hamster) uses more glucose and produces more lactic acid than the brain of homoiotherms (albino rat). One finds, therefore, in hibernators two metabolic manifestations which are known to increase the resistance to hypoxia and hypothermia.The study of ATP synthesis by isolated mitochondriae of the brain of hibernators shows that this synthesis is more intense in them than in homiotherms.The recording of cerebral waves indicates that during hibernation the cortex of hibernators remains excitable and manifests, either after external disturbances or without any apparent cause, periods of electrogenesis.The role of the nervous system as an integrator of the arousal mechanism has clearly appeared in the researches on the electric activity of the various subcortical systems.Hibernation appears as a metabolic regulation at a minimum level (Wyss ⁶¹), a regulation in which the role of central nervous system is capital: its functional suppression, e.g. by anesthesia, leads to fatal hypothermias (Benedict andLee ⁶²,Kayser ⁶³,Strumwasser ⁴⁰).

---

Résumé Le sommeil hivernal est une régulation métabolique à minimum (Wyss ⁶¹). Cette régulation exige une température optimale de l'ambiance audessus et au-dessous de laquelle les échanges respiratoires de l'hibernant sont augmentés.Le système nerveux central est responsable de cette régulation: si l'on supprime l'activité des centres nerveux de l'hibernant par des anesthésiques on supprime sa faculté de régler ses échanges et l'hibernant meurt en hypothermie (Benedict etLee ⁶²).Les centres nerveux de l'hibernant en sommeil hivernal restent excitables en dépit de la profonde hypothermie. L'hibernant partage cette faculté avec les homéothermes nouveau-nés, incomplètement développés. La résistance des centres nerveux à l'hypothermie se trouve associée dans les deux cas à une résistance accrue à l'hypoxie.L'étude du métabolisme cellulaire de la substance nerveuse des hibernants et des mammifères nouveaunés révèle une consommation de glucose et une production d'acide lactique accrues. Vu que le blocage de la consommation de glucose et de la glycolyse supprime la résistance à l'hypoxie, il est naturel d'attribuer la résistance spéciale du système nerveux des hibernants et des jeunes mammifères à cette particularité métabolique.L'intensité de la formation de l'acide adényl-triphosphorique par les mitochondries des cellules nerveuses des hibernants est aussi plus marquée que chez les homéothermes de même taille pris comme témoins. Cette seconde manifestation semble aussi correspondre à une adaptation particulière de l'activité des centres nerveux des hibernants à des conditions de fonctionnement spéciales.Le sommeil hivernal ne s'explique pas uniquement par les particularités fonctionnelles du système nerveux des hibernants. Le sommeil hivernal est une manifestation saisonnière liée à des facteurs externes (température, lumière, nourriture) et à des facteurs internes (cycle saisonnier des glandes endocrines;Kayser ⁵⁹). Mais seules les particularités fonct onnelles du système nerveux des hibernants autorisent une adaptation de l'hibernant aux conditions de vie en hypothermie. C'est la raison pour laquelleBullard et al.⁶⁰ ont pu réaliser chez un Spermophile américain ce qu'ils ont appelé le «Neural state of hibernation». C'est la même raison qui permet la survie de 30 jours en hypothermie du Lérot à jeun vivant à +5°C en été (Kayser ²³), avec une dépense d'énergie qui ne diffère à peu près pas de celle du Lérot en hibernation en plein hiver.

     

Prenylated quinones in marine sponges:Ircinia sp

Riassunto Viene descritto l'isolamento del 2-tetraprenil-1,4-benzochinone, del corrispondente idrochinone e dell' acido 4-idrossi-3-tetraprenilbenzoico dalla spugnaIrcinia muscarum. Il rinvenimento di quest'ultimo suggerisce che il precursore dell'anello dei chinoni prenilati non sostituiti e dei loro corrispondenti idrochinoni, ritrovati nelle spugne, sia l'acidop-idrossibenzoico, come nel caso degli ubichinoni. Vengono, inoltre, riportate alcune considerazioni sulle possibili relazioni biogenetiche nelle spugne tra gli ubichinoni e questi insoliti chinoni.     

Initial genome sequencing and analysis of multiple myeloma

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.     

Downregulation of enkephalin-mediated inflammatory responses by CD10/neutral endopeptidase 24.11.

The antigen CD10 (common acute lymphoblastic leukaemia antigen), which is the zinc metalloprotease, neutral endopeptidase 24.11 (also known as NEP or 'enkephalinase'), is expressed by acute lymphoblastic leukaemias, normal lymphoid progenitors, mature polymorphonuclear leukocytes and certain nonhaematopoietic cells. CD10/NEP hydrolyses several naturally occurring peptides, including the endogenous opioid pentapeptides Met- and Leu-enkephalin. In invertebrate organisms such as the mollusc Mytilus edulis, Met-enkephalin triggers inflammatory responses by inducing morphological changes, directed migration and aggregation of haemocytes. We report here that a structure related to CD10/NEP is expressed by M. edulis haemocytes and that abrogation of CD10/NEP enzymatic activity reduces the amount of Met-enkephalin required for haemocyte activation by five orders of magnitude. Similar results are obtained with CD10+ human polymorphonuclear leukocytes, indicating that CD10/NEP related structures regulate enkephalin-mediated inflammatory responses in organisms whose ancestors diverged approximately 500 million years ago.