Regioselectivity in the oxidative deamination of 2-methyl-1,4-diaminobutane catalyzed by diamine oxidases

Summary Diamine oxidase from pea seedlings (PDAO) catalyzes the oxidation of 2-methyl-1,4-diaminobutane in a regioselective fashion, whereas diamine oxidase from pig kidney (KDAO) shows no regioselectivity for the same reaction.This work was supported by Ministero della Pubblica Istruzione. We thank Prof. A. Fiecchi and Prof. S. Ronchi for many helpful discussions.     

Behavioural improvements with thalamic stimulation after severe traumatic brain injury

Widespread loss of cerebral connectivity is assumed to underlie the failure of brain mechanisms that support communication and goal-directed behaviour following severe traumatic brain injury. Disorders of consciousness that persist for longer than 12 months after severe traumatic brain injury are generally considered to be immutable; no treatment has been shown to accelerate recovery or improve functional outcome in such cases. Recent studies have shown unexpected preservation of large-scale cerebral networks in patients in the minimally conscious state (MCS), a condition that is characterized by intermittent evidence of awareness of self or the environment. These findings indicate that there might be residual functional capacity in some patients that could be supported by therapeutic interventions. We hypothesize that further recovery in some patients in the MCS is limited by chronic underactivation of potentially recruitable large-scale networks. Here, in a 6-month double-blind alternating crossover study, we show that bilateral deep brain electrical stimulation (DBS) of the central thalamus modulates behavioural responsiveness in a patient who remained in MCS for 6 yr following traumatic brain injury before the intervention. The frequency of specific cognitively mediated behaviours (primary outcome measures) and functional limb control and oral feeding (secondary outcome measures) increased during periods in which DBS was on as compared with periods in which it was off. Logistic regression modelling shows a statistical linkage between the observed functional improvements and recent stimulation history. We interpret the DBS effects as compensating for a loss of arousal regulation that is normally controlled by the frontal lobe in the intact brain. These findings provide evidence that DBS can promote significant late functional recovery from severe traumatic brain injury. Our observations, years after the injury occurred, challenge the existing practice of early treatment discontinuation for patients with only inconsistent interactive behaviours and motivate further research to develop therapeutic interventions.     

Co-existence of a guanidine-dependence and of a thiopyrimidine dependence in the same strain of poliovirus

Riassunto Una doppia dipendenza nei confronti della guanidina e di una tiopirimidina (S-7) può essere indotta in uno stesso stipite di poliovirus 1.     

Regulation of the bacterial cell cycle by an integrated genetic circuit

How bacteria regulate cell cycle progression at a molecular level is a fundamental but poorly understood problem. In Caulobacter crescentus, two-component signal transduction proteins are crucial for cell cycle regulation, but the connectivity of regulators involved has remained elusive and key factors are unidentified. Here we identify ChpT, an essential histidine phosphotransferase that controls the activity of CtrA, the master cell cycle regulator. We show that the essential histidine kinase CckA initiates two phosphorelays, each requiring ChpT, which lead to the phosphorylation and stabilization of CtrA. Downregulation of CckA activity therefore results in the dephosphorylation and degradation of CtrA, which in turn allow the initiation of DNA replication. Furthermore, we show that CtrA triggers its own destruction by promoting cell division and inducing synthesis of the essential regulator DivK, which feeds back to downregulate CckA immediately before S phase. Our results define a single integrated circuit whose components and connectivity can account for the cell cycle oscillations of CtrA in Caulobacter.     

5-Iodo-2-deoxyuridine resistance of vaccinia viruses in cells endowed with thymidine kinase activity

Riassunto La IUdR resistenza che alcuni DNA virus manifestano in cellule dotate di timidino-kinasi può essere dovuta ad una accentuata retroinibizione di questo enzima ad opera di TTP.

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This work has been supported by a grant of the Consiglio Nazionale delle Ricerche (Roma).