The formation and organization of complex blood vessel networks rely on various biophysical forces, yet the mechanisms governing endothelial cell-cell interactions under different mechanical inputs are not well understood. Using the dorsal longitudinal anastomotic vessel (DLAV) in zebrafish as a model, we studied the roles of multiple biophysical inputs and cerebral cavernous malformation (CCM)-related genes in angiogenesis. Our research identifies heg1 and krit1 (ccm1) as crucial for the formation of endothelial cell-cell interfaces during anastomosis. In mutants of these genes, cell-cell interfaces are entangled with fragmented apical domains. A Heg1 live reporter demonstrated that Heg1 is dynamically involved in the oscillatory constrictions along cell-cell junctions, whilst a Myosin live reporter indicated that heg1 and krit1 mutants lack actomyosin contractility along these junctions. In wild-type embryos, the oscillatory contractile forces at junctions refine endothelial cell-cell interactions by straightening junctions and eliminating excessive cell-cell interfaces. Conversely, in the absence of junctional contractility, the cell-cell interfaces become entangled and prone to collapse in both mutants, preventing the formation of a continuous luminal space. By restoring junctional contractility via optogenetic activation of RhoA, contorted junctions are straightened and disentangled. Additionally, haemodynamic forces complement actomyosin contractile forces in resolving entangled cell-cell interfaces in both wild-type and mutant embryos. Overall, our study reveals that oscillatory contractile forces governed by Heg1 and Krit1 are essential for maintaining proper endothelial cell-cell interfaces and thus for the formation of a continuous luminal space, which is essential to generate a functional vasculature.

Understanding the mechanisms behind the interaction of empathy for pain (EfP) and working memory (WM), particularly how they are influenced by social factors like perceived social distance (SD), is vital for comprehending how humans dynamically adapt to the complexities of social life. However, there is very little known about these mechanisms. Accordingly, we recruited 116 healthy participants to investigate the bidirectional influence and electrophysiological responses between WM and EfP, including the role of SD. Our research results revealed that the interaction between WM load and SD significantly influenced the processing of EfP. Specifically, high WM load and distant SD facilitated early processing of EfP. Conversely, low WM load and close SD promoted late processing of EfP. Further, the interaction between EfP and SD significantly influenced the performance of ongoing WM tasks. Specifically, the kin\'s pain, compared to kin\'s non-pain, improved participant\'s performance on low WM load tasks; however, it diminished participant\'s performance on tasks with high WM load. Overall, these results provide evidence at both behavioral and neural levels for the mutual influence of WM and EfP during the same temporal process, and SD emerged as a crucial moderating factor during these mutual influences.

Ongoing neural oscillations reflect cycles of excitation and inhibition in local neural populations, with individual neurons being more or less likely to fire depending upon the oscillatory phase. As a result, the oscillations could determine whether or not a sound is perceived and/or whether its neural representation enters into later processing stages. While empirical support for this idea has come from sound detection studies, large gaps in knowledge still exist regarding memory for sound events. In the current study, it was investigated how sensory entrainment impacts the fidelity of working memory representations for pitch. In two separate experiments, an 8 Hz amplitude modulated (AM) entraining stimulus was presented prior to a multitone complex having an f0 between 270 and 715 Hz. This \"target\" sound could be presented at phases from 0 to 2π radians in relation to the previous AM. After a retention interval of 4 s (Experiment 1; n = 26) or 2 s (Experiment 2; n = 28), listeners were tasked to reproduce the target sound\'s pitch by moving their finger along the horizontal axis of a response pad. It was hypothesized that if entrainment modulates auditory working memory fidelity, reproductions of a target\'s pitch would be more accurate and precise when targets were presented in phase with the entrainment. Cosine fits of the average data for both experiments showed a significant entrainment \"echo\" in the accuracy of pitch matches. There was no apparent echo in the matching precision. Fitting of the individual data accuracy showed that the optimal phase was consistent across individuals, aligning near the next AM peak had the AM continued. The results show that sensory entrainment modulates auditory working memory in addition to stimulus detection, consistent with the proposal that ongoing neural oscillatory activity modulates higher-order auditory processes.

BACKGROUND: Recent interest in how neural oscillations reflect the flow of information through the brain has led to partitioning electroencephalography (EEG) recordings into periodic (i.e., oscillatory) and aperiodic (i.e., non-oscillatory) components. While both contribute to conventional measures of power within the frequencies that compose EEG recordings, the periodic aspect characterizes true oscillations - the speed of which is thought to be critical to efficient functioning of neural systems. Given evidence of EEG power abnormalities in schizophrenia, we sought to determine if the periodic aspect of EEG was aberrant in people with schizophrenia (SCZ) and could serve as a general measure of brain efficiency.
METHODS: Resting state EEGs were gathered from 104 SCZ and 105 healthy control participants. We used the fitting-oscillations-and-one-over-f (FOOOF) toolbox to remove aperiodic neural activity. We computed the cross-correlation between power spectra for individual participants and the mean power spectrum for all participants to quantify the relative speed of neural oscillations.
RESULTS: Periodic activity in SCZ was shifted toward lower frequencies compared to control participants during eyes closed rest. On average SCZ had a 0.55 Hz shift toward oscillatory slowing across the frequency spectrum which predicted worse perceptual reasoning. Slower neural oscillations were associated with weaker perceptual reasoning within SCZ.
CONCLUSIONS: Slowed periodic activity at rest is evident in schizophrenia and may represent inefficient functioning of neural circuits as reflected in worse perceptual reasoning. A slower pace of neural oscillations may be a general limitation on the transmission of information within the brain.

Chronic neuropathic pain (CNP) remains a significant clinical challenge, with complex neurophysiological underpinnings that are not fully understood. Identifying specific neural oscillatory patterns related to pain perception and interference can enhance our understanding and management of CNP. To analyze resting electroencephalography data from individuals with chronic neuropathic pain to explore the possible neural signatures associated with pain intensity, pain interference, and specific neuropathic pain characteristics. We conducted a secondary analysis from a cross-sectional study using electroencephalography data from a previous study, and Brief Pain Inventory from 36 patients with chronic neuropathic pain. For statistical analysis, we modeled a linear or logistic regression by dependent variable for each model. As independent variables, we used electroencephalography data with such brain oscillations: as delta, theta, alpha, and beta, as well as the oscillations low alpha, high alpha, low beta, and high beta, for the central, frontal, and parietal regions. All models tested for confounding factors such as age and medication. There were no significant models for Pain interference in general activity, walking, work, relationships, sleep, and enjoyment of life. However, the model for pain intensity during the past four weeks showed decreased alpha oscillations, and increased delta and theta oscillations were associated with decreased levels of pain, especially in the central area. In terms of pain interference in mood, the model showed high oscillatory Alpha signals in the frontal and central regions correlated with mood impairment due to pain. Our models confirm recent findings proposing that lower oscillatory frequencies, likely related to subcortical pain sources, may be associated with brain compensatory mechanisms and thus may be associated with decreased pain levels. On the other hand, higher frequencies, including alpha oscillations, may disrupt top-down compensatory mechanisms.

Urethral smooth muscle cells (USMC) contract to occlude the internal urethral sphincter during bladder filling. Interstitial cells also exist in urethral smooth muscles and are hypothesized to influence USMC behaviours and neural responses. These cells are similar to Kit+ interstitial cells of Cajal (ICC), which are gastrointestinal pacemakers and neuroeffectors. Isolated urethral ICC-like cells (ICC-LC) exhibit spontaneous intracellular Ca2+ signalling behaviours that suggest these cells may serve as pacemakers or neuromodulators similar to ICC in the gut, although observation and direct stimulation of ICC-LC within intact urethral tissues is lacking. We used mice with cell-specific expression of the Ca2+ indicator, GCaMP6f, driven off the endogenous promoter for Kit (Kit-GCaMP6f mice) to identify ICC-LC in situ within urethra muscles and to characterize spontaneous and nerve-evoked Ca2+ signalling. ICC-LC generated Ca2+ waves spontaneously that propagated on average 40.1 ± 0.7 μm, with varying amplitudes, durations, and spatial spread. These events originated from multiple firing sites in cells and the activity between sites was not coordinated. ICC-LC in urethra formed clusters but not interconnected networks. No evidence for entrainment of Ca2+ signalling between ICC-LC was obtained. Ca2+ events in ICC-LC were unaffected by nifedipine but were abolished by cyclopiazonic acid and decreased by an antagonist of Orai Ca2+ channels (GSK-7975A). Phenylephrine increased Ca2+ event frequency but a nitric oxide donor (DEA-NONOate) had no effect. Electrical field stimulation (EFS, 10 Hz) of intrinsic nerves, which evoked contractions of urethral rings and increased Ca2+ event firing in USMC, failed to evoke responses in ICC-LC. Our data suggest that urethral ICC-LC are spontaneously active but are not regulated by autonomic neurons.

A chemical reaction and its reaction environment are intrinsically linked, especially within the confines of narrow cellular spaces. Traditional models of chemical reactions often use differential equations with concentration as the primary variable, neglecting the density heterogeneity in the solution and the interaction between the reaction and its environment. We model the interaction between a chemical reaction and its environment within a geometrically confined space, such as inside a cell, by representing the environment through the size of molecular clusters. In the absence of fluctuations, the interplay between cluster size changes and the activation and inactivation of molecules induces oscillations. However, in unstable environments, the system reaches a fluctuating steady state. When an enzyme is introduced to this steady state, oscillations akin to action potential spike trains emerge. We examine the behavior of these spike trains and demonstrate that they can be used to implement logic gates. We discuss the oscillations and computations that arise from the interaction between a chemical reaction and its environment, exploring their potential for contributing to chemical intelligence.

The basolateral amygdala plays pivotal roles in the regulation of fear and anxiety and these processes are profoundly modulated by different neuromodulatory systems that are recruited during emotional arousal. Recent studies suggest activities of BLA interneurons and inhibitory synaptic transmission in BLA principal cells are regulated by neuromodulators to influence the output and oscillatory network states of the BLA, and ultimately the behavioral expression of fear and anxiety. In this review, we first summarize a cellular mechanism of stress-induced anxiogenesis mediated by the interaction of glucocorticoid and endocannabinoid signaling at inhibitory synapses in the BLA. Then we discuss cell type-specific activity patterns induced by neuromodulators converging on the Gq signaling pathway in BLA perisomatic parvalbumin-expressing (PV) and cholecystokinin-expressing (CCK) basket cells and their effects on BLA network oscillations and fear learning.

Neural stem cells (NSCs) differentiate into neuron-fated intermediate progenitor cells (IPCs) via cell division. Although differentiation from NSCs to IPCs is a discrete process, recent transcriptome analyses identified a continuous transcriptional trajectory during this process, raising the question of how to reconcile these contradictory observations. In mouse NSCs, Hes1 expression oscillates, regulating the oscillatory expression of the proneural gene Neurog2, while Hes1 expression disappears in IPCs. Thus, the transition from Hes1 oscillation to suppression is involved in the differentiation of NSCs to IPCs. Here, we found that Neurog2 oscillations induce the accumulation of Tbr2, which suppresses Hes1 expression, generating an IPC-like gene expression state in NSCs. In the absence of Tbr2, Hes1 expression is up-regulated, decreasing the formation of IPCs. These results indicate that the Neurog2-Tbr2 axis forms a continuous transcriptional trajectory to an IPC-like neurogenic state in NSCs, which then differentiate into IPCs via cell division.

The AA profile of MP affects mammary gland metabolism and milk N efficiency of dairy cattle. Further, the frequency of dietary protein supplementation may influence N partitioning leading to reduced N excretion. This study investigated the effect of source and frequency of rumen-protected (RP) protein supplementation on apparent total-tract digestibility, milk production, mammary gland AA metabolism, and N balance of dairy cattle. Twenty-eight Holstein-Friesian cows (2.3 ± 0.9 lactations; 93 ± 27 DIM; mean ± SD) were used in a randomized complete block design and fed a basal TMR consisting of 41% corn silage, 32% grass silage, and 27% concentrate (DM basis) and formulated to meet 100% and 95% of net energy and MP requirements, respectively. Cows were adapted to the basal TMR in a freestall barn for 7 d, moved to individual tiestalls for 13 d of adaptation to dietary treatments, and then moved into climate respiration chambers for a 4-d measurement period. Treatments consisted of the basal TMR (CON; 159 g CP/kg DM) or the basal TMR including 1 of 3 iso-MP supplements: (1) 315-g mixture of RP soybean meal and RP rapeseed meal fed daily (ST-RPSR), (2) 384-g mixture of RP His, RP Lys, and RP Met fed daily (ST-RPAA), and (3) 768-g mixture of RP His, RP Lys, and RP Met fed every other day (OS-RPAA). The basal TMR with the addition of treatment supplements was designed to deliver 100% of required MP over a 48-h period. The mixture of His, Lys, and Met was formulated to deliver digestible AA in amounts relative to their concentration in casein. Compared with ST-RPSR, ST-RPAA increased milk protein and fat concentration, increased the arterial concentration of total His, Lys, and Met (HLM), decreased mammary clearance of HLM, and increased clearance of Phe, Leu, and Tyr (tendency for Leu and Tyr). Rumen-protected protein source did not affect N balance, but the marginal use efficiency (efficiency of transfer of RP protein supplement into milk protein) of ST-RPAA (67%) was higher than that of ST-RPSR (17%). Milk protein concentration decreased with OS-RPAA compared with ST-RPAA. Arterial concentration of HLM increased on the nonsupplemented day compared with the supplemented day with OS-RPAA, and there was no difference in arterial HLM concentration across days with ST-RPAA. Mammary uptake of HLM tended to increase on the nonsupplemented day compared with the supplemented day with OS-RPAA. Supplementation frequency of RP AA did not affect N balance or overall milk N efficiency, but the marginal use efficiency of OS-RPAA (49%) was lower compared with ST-RPAA. Overall, mammary glands responded to an increased supply of His, Lys, and Met by reducing efflux of other EAA when RP His, RP Lys, and RP Met were supplemented compared with RP plant proteins. Mammary glands increased sequestration of EAA (primarily HLM) on the nonsupplemented day with OS-RPAA, but supplementing RP AA according to a 24-h oscillating pattern did not increase N efficiency over static supplementation.