We share reviews on Nature and Science Journal articles that we found the most interesting this month. Here is the second part of the June reviews. Today we observe neurophysiology, drug research, and structural biology.
K. Shatalin, A. Nuthanakanti, A. Kaushik, et al. Inhibitors of bacterial H2S production potentiate antibiotics, reverse resistance, and block the generation of persister cells. Science 6547, 1169-1175 (2021)
Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Persister cells, which are found in abundance in biofilms, adopt a quiescent state and survive antimicrobial treatments, seeding disease recurrence. In their new study, scientists found an effective antimicrobial strategy. Shatalin et al. conducted a structure-based screen for inhibitors that block a bacterial hydrogen sulfide–producing enzyme and found an interesting group of inhibitors. These inhibitors potentiated bactericidal antibiotics and they also suppressed persister bacteria. This strategy may be promising for treating recalcitrant infections and holding the line against drug-resistant bacteria.
B. Zhao, T. Li, Y. Yang, et al. A large-scale tract-specific study elucidates the genetic architecture of brain white matter and its links to a wide spectrum of clinical outcomes. Science 6548, eabf3736 (2021)
One of the most enduring themes in human neuroscience is the association of higher brain functions such as cognition and emotion with gray matter. Other regions relevant to behavior include the white matter that interconnects brain
structures. On pages of Science, Zhao et al. present compelling evidence for the importance of white matter by demonstrating genetic influences on structural connectivity. The authors identified structural and genetic abnormalities associated with neurological and psychiatric disorders, thus creating a valuable resource and providing some insights into the underlying neurobiology.
A. Ibrahim, C. Papin, K. Mohideen-Abdul, et al. The Rett syndrome protein MeCP2 is a DNA microsatellite CA repeat–binding protein that regulates chromatin architecture. Science 6549, eabd5581 (2021)
Rett syndrome is a severe neurodevelopmental disorder that is mainly caused by mutations in the methyl-CpG-binding protein 2 gene (MeCP2). In their new study, Ibrahim et al. show that MeCP2 is a protein that may bind to DNA sequences and modulate chromatin architecture. MeCP2 accumulates and spreads around modified CA DNA repeats. Loss of MeCP2 results in transcriptional dysregulation of genes enriched in CA repeats. These results shed light on the underlying molecular mechanism of Rett syndrome, a severe disease associated with mutations in MeCP2, and hold out hope for new, more effective therapies.
Collier, D.A., Ferreira, I.A.T.M., Kotagiri, P. et al. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature (2021)
Two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, but there is little information about vaccine efficacy in individuals above eighty years of age. In a new study, scientists analyzed immune responses following vaccination with the BNT162b2 mRNA vaccine in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. However, following the second dose, neutralization against VOC was detectable regardless of age. Authors conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted.
Wu, WL., Adame, M.D., Liou, CW. et al. Microbiota regulate social behaviour via stress response neurons in the brain. Nature 595, 409–414 (2021)
The gut microbiota contributes to social activity in mice, including mating, nurturing, and defense, but the gut-brain connections that regulate this complex behaviour and its underlying neural basis are unclear. In their new article scientists show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone. These studies show that the microbiome can affect social behaviours through discrete neuronal circuits that mediate stress responses in the brain.