©Inra

Researchers at the French National Institute for Agricultural Research (Inra) and Inserm have discovered a new family of bacterial enzymes that can produce hitherto unidentified peptides with antibiotic activity. Published in Nature Chemistry, this work holds promise for the synthesis of molecules of pharmaceutical interest and the design of new antibiotics.

As part of research involving study of the enzymes of the gut microbiota, researchers from Inra and Inserm studied the model bacterium Bacillus subtilis. Genetic analysis of the organism showed the presence of genes conserved by common bacteria from the gut microbiota, such as enterococci. *

The scientists were especially interested in two Bacillus subtilis genes potentially coding for a peptide and an enzyme from the superfamily known as “radical SAM enzymes.” Their work has made it possible to describe a new enzyme mechanism that can transform a peptide into a bioactive molecule. Known as epimerisation, this enzymic transformation brings about a change in the configuration of certain amino acid residues from the L- configuration (normally found in peptides) to the D-configuration. The researchers discovered how this enzyme works: it removes a hydrogen atom from the alpha-carbon atom of the amino acid residues and donates another, bringing about their epimerisation. It is a mechanism not previously described in nature.

It is the first time that researchers have demonstrated the ability of “radical SAM” enzymes to catalyse epimerisation within a peptide in vitro. Surprisingly, the peptide thus modified and called an “epipeptide” is able to inhibit growth of Bacillus subtilis very effectively. These epipeptides thus represent a new class of natural products that might be used to develop new antibiotics against Gram positive bacteria (such as staphylococci, enterococci or streptococci), which are becoming increasingly antibiotic resistant, constituting a major public health problem.

© Fotolia

Postural instability is the main factor associated with falls in patients with Parkinson disease, but there are other symptoms, such eye disorders. Teams from Pitié-Salpêtrière Hospital, AP-HP, and the Brain and Spine Institute (Inserm, CNRS, UPMC) have examined the link between these eye disorders observed in some patients and postural instability. Their results demonstrate a potential new marker of posture control in Parkinson disease. These results are published in the journal Neurology.

Some patients with Parkinson disease show impairment of the voluntary eye movements, the “antisaccades.” Dr Claire Ewenczyk, from the team led by Prof Marie Vidailhet, and Prof. Stéphane Lehéricy, from the Brain and Spine Institute, (Inserm, CNRS, UPMC) at Pitié-Salpêtrière Hospital, AP-HP, conducted a study in 30 patients with Parkinson’s disease with or without postural control disorders, and 25 healthy subjects.

The researchers examined the patients’ walk and balance, and recorded the initiation of walking and eye movements. At the same time, they studied the interactions between two areas of the brain: the frontal oculomotor area, which plays an important role in visual attention and eye movements, and the mesencephalic locomotor area, which is strongly involved in the control of posture and eye movements.

Their results indicate that patients with posture disorders also show abnormal reaction time (latency) in their voluntary eye movements. This abnormality is correlated with an alteration in the parameters during initiation of a step, particularly the duration of anticipatory postural adjustments, mechanisms used by the central nervous system to maintain balance in a standing position while performing voluntary movements.

Studying the interactions between the frontal oculomotor and mesencephalic locomotor areas of the brain reveals, in healthy subjects, a correlation between the frontal connections of these areas and the latency of voluntary eye movements. In patients with Parkinson disease, this association disappears. This suggests extensive involvement of the mesencephalic area in the disease, which affects both posture control and eye movements.

The prolongation of the reaction time of eye movements or “antisaccades,” a simple and reliable parameter, might constitute a prognostic marker of postural control in Parkinson disease, and be used for patient assessment in future longitudinal studies.

©Alexandra Pinci pour l’Inserm

Not sleeping enough or going to bed too late leads to a reduction in the volume of grey matter in the brains of adolescents. These conclusions were obtained by researchers at Inserm Unit 1000, “Neuroimaging and Psychiatry” (Inserm/Paris-Descartes University/Paris Sud University), who studied the brain and sleep habits of 177 14-year-old students. This work is published in the journal Scientific Reports, and received support from the Academy of Finland.

Lack of sleep in adolescents can compromise their academic success, and their health and safety. Shortened or delayed sleep has consequences for academic performance. There is still debate over the time at which lessons should begin in order to benefit the health of adolescents. However, researchers did not know until now whether or not poor sleep habits in adolescents were associated with damage to the anatomy of the brain.

A collaboration between researchers from Inserm and from the Finnish National Institute for Health and Welfare, supported by the Academy of Finland, shows for the first time a link between sleep habits and brain structure in young adolescents.

The researchers studied the sleep habits of 177 14-year-old students attending secondary schools in the Paris region. On average, the adolescents went to bed at 10:20 pm on week nights and got up at 7:06 am, and went to bed at 11:30 pm at weekends, getting up at 9:45 am. But there were large discrepancies between the adolescents.

©Alexandra Pinci pour l’Inserm

The researchers found that a short period of sleep (less than 7 h) during the week, and going to bed an hour later at weekends were correlated with smaller volumes of grey matter in several regions of the brain (the frontal cortex, anterior cingulate cortex and precuneus). “The most significant result from our study is very definitely the finding that the later the adolescents go to bed at weekends, the greater the reduction in their volume of grey matter,” explains Jean Luc Martinot, Inserm Research Director and last author of this work.

These 3 regions of the brain are particularly involved in attention, concentration, and ability to multitask. Moreover, the researchers observed an association between poor grades obtained by students and smaller amounts of grey matter in their frontal regions, the regions in which the volume is reduced by late bedtimes at weekends.

©Alexandra Pinci pour l’Inserm

These results show that there is a link between poor sleep habits, brain structure (still actively undergoing peripubertal maturation), and poor academic performance.

For the researchers, this study suggests making sure that adolescents acquire good sleep habits during this period of brain maturation. “We encourage parents, social workers and school liaison officers to promote the maintenance of a good sleep-wake routine for adolescents. In particular, avoiding routinely late bedtimes during weekends seems important for optimising the brain’s potential for development and for supporting academic success,” concludes Jean-Luc Martinot.