The predominant role of the primary motor cortex (M1) in motor execution is well acknowledged. However, additional roles of M1 are getting evident in humans owing to advances in noninvasive brain stimulation (NIBS) techniques. This review collates such studies in humans and proposes that M1 also plays a key role in higher cognitive processes. The review commences with the studies that have investigated the nature of connectivity of M1 with other cortical regions in light of studies based on NIBS. The review then moves on to discuss the studies that have demonstrated the role of M1 in higher cognitive processes such as attention, motor learning, motor consolidation, movement inhibition, somatomotor response, and movement imagery. Overall, the purpose of the review is to highlight the additional role of M1 in motor cognition besides motor control, which remains unexplored.
Gram-negative
bacteria are becoming resistant to almost all currently
available antibiotics. Systemically designed antimicrobial peptides
(AMPs) are attractive agents to enhance the activities of antibiotics.
We constructed a small Pro-scanning library using amphipathic model
peptides. Measurements of minimum inhibitory concentration (MIC) against Escherichia coli and hemolytic activities showed
that one of the Pro-hinged peptides, KL-L9P, displays the highest
specificity toward E. coli. Moreover,
KL-L9P sensitizes E. coli to be responsive
to most antibiotics that are not active against Gram-negative bacteria.
The results of biochemical experiments show that KL-L9P promotes the
rearrangement of the bacterial membrane that enables hydrophobic antibiotics
to permeate. Finally, the results of animal tests demonstrate that
KL-L9P strongly sensitizes Gram-negative bacteria to linezolid (Lzd),
rifampicin (Rif), or clarithromycin (Clr). Thus, KL-L9P operates as
a sensitizer to extend the antibacterial activity of most antibiotics
to Gram-negative bacteria.
A novel microbial esterase, EaEST, from a psychrophilic bacterium Exiguobacterium antarcticum B7, was identified and characterized. To our knowledge, this is the first report describing structural analysis and biochemical characterization of an esterase isolated from the genus Exiguobacterium. Crystal structure of EaEST, determined at a resolution of 1.9 Å, showed that the enzyme has a canonical α/β hydrolase fold with an α-helical cap domain and a catalytic triad consisting of Ser96, Asp220, and His248. Interestingly, the active site of the structure of EaEST is occupied by a peracetate molecule, which is the product of perhydrolysis of acetate. This result suggests that EaEST may have perhydrolase activity. The activity assay showed that EaEST has significant perhydrolase and esterase activity with respect to short-chain p-nitrophenyl esters (≤C8), naphthyl derivatives, phenyl acetate, and glyceryl tributyrate. However, the S96A single mutant had low esterase and perhydrolase activity. Moreover, the L27A mutant showed low levels of protein expression and solubility as well as preference for different substrates. On conducting an enantioselectivity analysis using R- and S-methyl-3-hydroxy-2-methylpropionate, a preference for R-enantiomers was observed. Surprisingly, immobilized EaEST was found to not only retain 200% of its initial activity after incubation for 1 h at 80°C, but also retained more than 60% of its initial activity after 20 cycles of reutilization. This research will serve as basis for future engineering of this esterase for biotechnological and industrial applications.
Repetitive transcranial magnetic stimulation (rTMS) influences the brain temporally beyond the stimulation period and spatially beyond the stimulation site. Application of rTMS over the primary motor cortex (M1) has been shown to lead to plastic changes in interregional connectivity over the motor system as well as alterations in motor performance. With a sequential combination of rTMS over the M1 and functional magnetic resonance imaging (fMRI), we sought changes in the topology of brain networks and specifically the association of brain topological changes with motor performance changes. In a sham-controlled parallel group experimental design, real or sham rTMS was administered to each of the 15 healthy subjects without prior motor-related dysfunctions, over the right M1 at a high frequency of 10 Hz. Before and after the intervention, fMRI data were acquired during a sequential finger motor task using the left, nondominant hand. Changes in the topology of brain networks were assessed in terms of global and local efficiency, which measures the efficiency in transporting information at global and local scales, respectively, provided by graph-theoretical analysis. Greater motor performance changes toward improvements after real rTMS were shown in individuals who exhibited more increases in global efficiency and more decreases in local efficiency. The enhancement of motor performance after rTMS is supposed to be associated with brain topological changes, such that global information exchange is facilitated, while local information exchange is restricted.
Edited by Miguel De la RosaCarbohydrate acetylesterases, which have a highly specific role among plant-interacting bacterial species, remove the acetyl groups from plant carbohydrates. Here, we determined the crystal structure of Est24, an octameric carbohydrate acetylesterase from Sinorhizobium meliloti, at 1.45 A resolution and investigated its biochemical properties. The structure of Est24 consisted of five parallel b strands flanked by a helices, which formed an octameric assembly with two distinct interfaces. The deacetylation activity of Est24 and its mutants around the substrate-binding pocket was investigated using several substrates, including glucose pentaacetate and acetyl alginate. Elucidation of the structure-function relationships of Est24 could provide valuable opportunities for biotechnological explorations.
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