Structural basis of chorismate isomerization by Arabidopsis ISOCHORISMATE SYNTHASE1.

Salicylic acid (SA) plays a crucial role in plant defense against biotrophic and semi-biotrophic pathogens. In Arabidopsis (Arabidopsis thaliana), isochorismate synthase 1 (AtICS1) is a key enzyme for the pathogen-induced biosynthesis of SA via catalytic conversion of chorismate into isochorismate, an essential precursor for SA synthesis. Despite the extensive knowledge of ICS1-related menaquinone, siderophore, tryptophan (MST) enzymes in bacteria, the structural mechanisms for substrate binding and catalysis in plant isochorismate synthase (ICS) enzymes are unknown. This study reveals that plant ICS enzymes catalyze the isomerization of chorismate through a magnesium-dependent mechanism, with AtICS1 exhibiting the most substantial catalytic activity. Additionally, we present high-resolution crystal structures of apo AtICS1 and its complex with chorismate, offering detailed insights into the mechanisms of substrate recognition and catalysis. Importantly, our investigation indicates the existence of a potential substrate entrance channel and a gating mechanism regulating substrate into the catalytic site. Structural comparisons of AtICS1 with MST enzymes suggest a shared structural framework with conserved gating and catalytic mechanisms. This work provides valuable insights into the structural and regulatory mechanisms governing substrate delivery and catalysis in AtICS1, as well as other plant ICS enzymes.

Structural basis for zinc-induced activation of a zinc uptake transcriptional regulator.

The zinc uptake regulator (Zur) is a member of the Fur (ferric uptake regulator) family transcriptional regulators that plays important roles in zinc homeostasis and virulence of bacteria. Upon zinc perception, Zur binds to the promoters of zinc responsive genes and controls their transcription. However, the mechanism underlying zinc-mediated Zur activation remains unclear. Here we report a 2.2-Å crystal structure of apo Zur from the phytopathogen Xanthomonas campestris pv. campestris (XcZur), which reveals the molecular mechanism that XcZur exists in a closed inactive state before regulatory zinc binding. Subsequently, we present a 1.9-Å crystal structure of holo XcZur, which, by contrast, adopts an open state that has enough capacity to bind DNA. Structural comparison and hydrogen deuterium exchange mass spectrometry (HDX-MS) analyses uncover that binding of a zinc atom in the regulatory site, formed by the hinge region, the dimerization domain and the DNA binding domain, drives a closed-to-open conformational change that is essential for XcZur activation. Moreover, key residues responsible for DNA recognition are identified by site-directed mutagenesis. This work provides important insights into zinc-induced XcZur activation and valuable discussions on the mechanism of DNA recognition.

EEG microstates are correlated with brain functional networks during slow-wave sleep.

Electroencephalography (EEG) microstates have been extensively studied in wakefulness and have been described as the "atoms of thought". Previous studies of EEG have found four microstates, i.e., microstates A, B, C and D, that are consistent among participants across the lifespan during the resting state. Studies using simultaneous EEG and functional magnetic resonance imaging (fMRI) have provided evidence for correlations between EEG microstates and fMRI networks during the resting state. Microstates have also been found during non-rapid eye movement (NREM) sleep. Slow-wave sleep (SWS) is considered the most restorative sleep stage and has been associated with the maintenance of sleep. However, the relationship between EEG microstates and brain functional networks during SWS has not yet been investigated. In this study, simultaneous EEG-fMRI data were collected during SWS to test the correspondence between EEG microstates and fMRI networks. EEG microstate-informed fMRI analysis revealed that three out of the four microstates showed significant correlations with fMRI data: 1) fMRI fluctuations in the insula and posterior temporal gyrus positively correlated with microstate B, 2) fMRI signals in the middle temporal gyrus and fusiform gyrus negatively correlated with microstate C, and 3) fMRI fluctuations in the occipital lobe negatively correlated with microstate D, while fMRI signals in the anterior cingulate and cingulate gyrus positively correlated with this microstate. Functional brain networks were then assessed using group independent component analysis based on the fMRI data. The group-level spatial correlation analysis showed that the fMRI auditory network overlapped the fMRI activation map of microstate B, the executive control network overlapped the fMRI deactivation of microstate C, and the visual and salience networks overlapped the fMRI deactivation and activation maps of microstate D. In addition, the subject-level spatial correlations between the general linear model (GLM) beta map of each microstate and the individual maps of each component yielded by dual regression also showed that EEG microstates were closely associated with brain functional networks measured using fMRI during SWS. Overall, the results showed that EEG microstates were closely related to brain functional networks during SWS, which suggested that EEG microstates provide an important electrophysiological basis underlying brain functional networks.

Dynamic functional connectivity states characterize NREM sleep and wakefulness.

According to recent neuroimaging studies, temporal fluctuations in functional connectivity patterns can be clustered into dynamic functional connectivity (DFC) states and correspond to fluctuations in vigilance. However, whether there consistently exist DFC states associated with wakefulness and sleep stages and what are the characteristics and electrophysiological origin of these states remain unclear. The aims of the current study were to investigate the properties of DFC in different sleep stages and to explore the relationship between the characteristics of DFC and slow-wave activity. We collected both eyes-closed wakefulness and sleep data from 48 healthy young volunteers with simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings. EEG data were employed as the gold standard of sleep stage scoring, and DFC states were estimated based on fMRI data. The results demonstrated that DFC states of the fMRI signals consistently corresponded to wakefulness and nonrapid eye movement sleep stages independent of the number of clusters. Furthermore, the mean dwell time of these states significantly correlated with slow-wave activity. The inclusion or omission of regression of the global signal and the selection of parcellation schemes exerted minimal effects on the current findings. These results provide strong evidence that DFC states underlying fMRI signals match the fluctuations of vigilance and suggest a possible electrophysiological source of DFC states corresponding to vigilance states.

Brain structural basis of individual variability in dream recall frequency.

Recent neuroimaging studies have indicated that inter-individual variability in dream recall frequency (DRF) is associated with both resting-state regional cerebral blood flow and task-induced brain activations. However, the brain structure underpinning this inter-individual variability in DRF remains unclear. The aim of the current study is to investigate the relationship between brain structural characteristics and DRF. We collected both T1-weighted and diffusion tensor magnetic resonance imaging data from 43 healthy volunteers. DRF was obtained from a two-week sleep diary with a subjective report of dream recall upon waking every morning. General linear model analysis was used to evaluate the relationship between brain structural characteristics (cortical volume and white matter integrity) and DRF. Not only the cortical volume of the medial portion of the right fusiform gyrus and parahippocampal gyrus but also the fractional anisotropy of white matter fibers connected to these regions were significantly negatively correlated with DRF, and these relationships were not modulated by a regular sleep. These findings provide direct evidence that brain structural characteristics are associated with inter-individual variability in DRF and may help us to better understand the structural mechanisms in the brain underlying dream recall.

Dissociated resting-state functional networks between the dream recall frequency and REM sleep percentage.

Rapid eye movement (REM) sleep has been frequently associated with dreaming. However, mounting evidence obtained from behavioral, pharmacological, and brain imaging studies suggests that REM sleep is not indicative of the dream report and may originate from diverse neural substrates in brain functionality. The aim of the current study was to investigate the functional systems associated with inter-individual differences in dream recall and REM sleep through assessments of the resting-state functional connectivity. We collected resting-state functional magnetic resonance imaging (fMRI) data for functional connectivity evaluations from 43 healthy adult volunteers (23 men) before and after sleep. For assessment of the dream recall frequency, a 2-week sleep diary was maintained by all volunteers. In addition, whole-night polysomnography was performed for measuring the REM sleep percentage. Voxel-wise correlation analyses of 12 functional connectivity networks of interest with the dream recall frequency and REM sleep percentage were conducted using general linear model analysis. Both the dream recall frequency and REM sleep percentage showed negative associations with multiple brain functional networks. However, the dream recall frequency was mainly related to functional connectivity within the lateral visual network and thalamus, whereas the REM sleep percentage was mainly associated with connectivity within the frontoparietal networks and cerebellum. In addition, the dream recall frequency showed stronger coupling with the lateral visual network connectivity at night, whereas the coupling between the REM sleep percentage and cerebellum was higher in the morning. This indicated a significant time of day effect. Our results provide neuroimaging evidence that the functional system associated with the dream recall frequency is different from that associated with the REM sleep percentage.

Functional thalamocortical connectivity development and alterations in preterm infants during the neonatal period.

The thalamus is one of the most commonly affected brain regions in preterm infants, particularly in infants with white matter lesions (WML). The aim of this paper is to explore the development and alterations of the functional thalamocortical connectivity in preterm infants with and without punctate white matter lesions (PWMLs) during the period before term equivalent age (TEA). In this study, twenty-two normal preterm infants (NP), twenty-two preterm infants with PWMLs and thirty-one full-term control infants (FT) were enrolled. Thalamus parcellation was performed based on partial correlation between the thalamus and seven well-recognized infant networks obtained from independent component analysis (ICA), and thalamocortical connectivity was further reconstructed between the defined thalamus clusters and the whole brain. Thalamo-salience (SA) and thalamo-sensorimotor (SM) connectivity were predominantly identified, while other types of thalamocortical connectivity remained largely limited during the neonatal period. Both preterm groups exhibited prominent development in thalamo-SA and thalamo-SM connectivity during this period. Compared with NP infants, PWML infants demonstrated increased connectivity in the parietal area in thalamo-SA connectivity but no significant differences in thalamo-SM connectivity. Our results reveal that compared with NP infants, PWML infants exhibit slightly altered thalamo-SA connectivity, and this alteration is deduced to be functional compensations for inefficient thalamocortical processing due to PWMLs.