Late Component Research Articles

Neurophysiological markers that link genes and behavior in humans: examples from rare genetic syndromes associated with autism spectrum disorders

Rare genetic syndromes associated with autism spectrum disorders have several noninvasive neurophysiological markers that can be linked with molecular genetic characteristics and behavioral characteristics in these diseases. For the recently discovered Potocki–Lupski syndrome associated with disturbances on the 17p11.2 segment, a previously undescribed epileptiform activity was detected, characterized by a saw-like hypersynchronization at a frequency of 13 Hz, which may indicate a certain type of disturbance in the excitation/inhibition balance in neural networks. For a rare case of microduplication in SH3 and ankyrin repeat domains 3 (SHANK3), also associated with the Phelan–McDermid syndrome, we described a pathway from a violation in the functioning of the SHANK3 protein, through a distorted interaction of excitatory and inhibitory neurons, primarily associated with hypofunction of N-methyl-D-aspartate receptors on inhibitory neurons, to reduced temporal resolution in the auditory cortex, reflected in the absence of response following 40 Hz auditory stimulation (40 Hz auditory steady-state response) and underlying problems in speech development. For the Rett syndrome, which is caused by a mutation in methyl CpG binding protein 2 (MECP2), which has a very wide influence on many other genes, the neurophysiological findings were also diverse. Among the most promising are changes in sensorimotor rhythm, potentially associated with a key symptom of the disease, namely, stereotyped hand movements, as well as more delayed latency of the main components of the event-related potentials, which can have a cascading effect on information processing and affect the perception of basic information, including speech. This review focuses on the presentation of the concept of a neurophysiological profile, the construction of which can help not only to objectify the diagnosis of developmental disorders, but also in the construction of a mechanistic chain from gene to behavior.

The dissociation of semantically congruent and incongruent cross-modal effects on the visual attentional blink.

Recent studies have found that the sound-induced alleviation of visual attentional blink, a well-known phenomenon exemplifying the beneficial influence of multisensory integration on time-based attention, was larger when that sound was semantically congruent relative to incongruent with the second visual target (T2). Although such an audiovisual congruency effect has been attributed mainly to the semantic conflict carried by the incongruent sound restraining that sound from facilitating T2 processing, it is still unclear whether the integrated semantic information carried by the congruent sound benefits T2 processing. To dissociate the congruence-induced benefit and incongruence-induced reduction in the alleviation of visual attentional blink at the behavioral and neural levels, the present study combined behavioral measures and event-related potential (ERP) recordings in a visual attentional blink task wherein the T2-accompanying sound, when delivered, could be semantically neutral in addition to congruent or incongruent with respect to T2. The behavioral data clearly showed that compared to the neutral sound, the congruent sound improved T2 discrimination during the blink to a higher degree while the incongruent sound improved it to a lesser degree. The T2-locked ERP data revealed that the early occipital cross-modal N195 component (192-228 ms after T2 onset) was uniquely larger in the congruent-sound condition than in the neutral-sound and incongruent-sound conditions, whereas the late parietal cross-modal N440 component (400-500 ms) was prominent only in the incongruent-sound condition. These findings provide strong evidence that the modulating effect of audiovisual semantic congruency on the sound-induced alleviation of visual attentional blink contains not only a late incongruence-induced cost but also an early congruence-induced benefit, thereby demonstrating for the first time an unequivocal congruent-sound-induced benefit in alleviating the limitation of time-based visual attention.

Where Worlds Collide: Late Woodland Potting Practice and Social Interaction in Upstate South Carolina

AbstractMany anthropologists have now adopted a relational view of the culture concept. Much research has shown that, far from being bounded or self-replicating, cultures emerge through interactions between social Others. These findings are particularly important to research on borderlands and peripheries, where communities routinely encounter wide-ranging social and political diversity. We present ceramic frequencies alongside petrographic analysis from the Late Woodland component at Esseneca (38OC20) to illustrate two main points: (1) pottery types previously understood as culture historical isolates co-occur in parts of Upstate South Carolina, and (2) potters collected clays from two main geologic formations near the site. This research shows that communities in the region traveled freely, crossing cultural boundaries while acquiring potting clays. We suggest that this level of interaction between disparate social groups laid the foundation for some aspects of Mississippianization in the region.

Express detection of visual objects by primate superior colliculus neurons

Primate superior colliculus (SC) neurons exhibit visual feature tuning properties and are implicated in a subcortical network hypothesized to mediate fast threat and/or conspecific detection. However, the mechanisms through which SC neurons contribute to peripheral object detection, for supporting rapid orienting responses, remain unclear. Here we explored whether, and how quickly, SC neurons detect real-life object stimuli. We presented experimentally-controlled gray-scale images of seven different object categories, and their corresponding luminance- and spectral-matched image controls, within the extrafoveal response fields of SC neurons. We found that all of our functionally-identified SC neuron types preferentially detected real-life objects even in their very first stimulus-evoked visual bursts. Intriguingly, even visually-responsive motor-related neurons exhibited such robust early object detection. We further identified spatial frequency information in visual images as an important, but not exhaustive, source for the earliest (within 100 ms) but not for the late (after 100 ms) component of object detection by SC neurons. Our results demonstrate rapid and robust detection of extrafoveal visual objects by the SC. Besides supporting recent evidence that even SC saccade-related motor bursts can preferentially represent visual objects, these results reveal a plausible mechanism through which rapid orienting responses to extrafoveal visual objects can be mediated.

The impact of electrode selection for ocular correction on the reward positivity and late positive potential components in adolescents.

Electroencephalography (EEG) data processing to derive event-related potentials (ERPs) follows a standard set of procedures to maximize signal-to-noise ratio. This often includes ocular correction, which corrects for artifacts introduced by eye movements, typically measured by electrooculogram (EOG) using facial electrodes near the eyes. Yet, attaching electrodes to the face may be uncomfortable for some populations, best to avoid in some situations, and contribute to data loss. Eye movements can also be measured using electrodes in a standard 10-20 EEG cap. An examination of the impact of electrode selection on ERPs is needed to inform best practices. The present study examined data quality when using different electrodes to measure eye movements for ocular correction (i.e., facial electrodes, cap electrodes, and no ocular correction) for two well-established and widely studied ERP components (i.e., reward positivity, RewP; and late positive potential, LPP) elicited in adolescents (N = 34). Results revealed comparable split-half reliability and standardized measurement error (SME) between facial and cap electrode approaches, with lower SME for the RewP with facial or cap electrodes compared to no ocular correction. Few significant differences in mean amplitude of ERPs were observed, but the LPP to positive images differed when using facial compared to cap electrodes. Findings provide preliminary evidence of the ability to collect high-quality ERP data without facial electrodes. However, when using cap electrodes for EOG measurement and ocular correction, it is recommended to use consistent procedures across the sample or statistically examine the impact of ocular correction procedures on results.

Poster Session I: Comparison of tripolar and traditional electrodes: Waveform morphology.

The waveforms of visual evoked potentials (VEPs) recorded by tripolar electrodes are different from those recorded by traditional electrode arrays. Traditional arrays record potentials using both an active and a reference electrode. The location of this reference will affect the waveform amplitude and shape. Conversely, tripolar electrodes measure the surface Laplacian across three concentric rings housed within a single electrode surface. These differences may influence the morphology of evoked responses. We compared these two modalities by recording pattern-reversal VEPs to two sizes of checkerboard. Visual inspection of the VEPs suggest that the signals recorded by the tripolar system have attenuated higher frequencies and increased latency of the major waveform components. Root-mean-square comparison of the two signal types confirm attenuation at the higher frequencies in the tripolar recording. Additionally, there is a cumulative delay present within both the large and small check conditions, such that each subsequent component recorded by the tripolar electrodes is shifted increasingly later in time compared to the same components recoded by the traditional electrodes. Such latency shifts may be indicative of a difference in the physiological sources that are measured by the two EEG systems.

Late positive potential component and cognitive functioning in occipital area of Mild Cognitive Impairment

AbstractBackgroundMild Cognitive Impairment (MCI) is a prodromal stage of Alzheimer’s disease and other dementias (Langa & Levine, 2014). It has been suggested that a late event‐related potential (ERP) called the late positive potential (LPP) is related to cognitive functioning including sustained attention and reaction time in people with MCI (Waninger et al., 2018). The LPP in the occipital area was also suggested to be a biomarker of MCI (Liu et al., 2022). However, it remains unclear whether LPP in the occipital area is related to cognitive functioning.MethodWe collected EEG of 50 people with MCI (mean age 72.44±7.96; education: 5.52±1.07) by using a 20‐channel EEG recording system while participants performed the simple vigilance task (SVT). Their reaction time (ms) was taken as a measure of sustained attention. Vienna Reaction Time Task (VRTT) (Schuhfried GmbH, Moedling, Austria) was used to measure processing speed and inhibition while separating motor action (measured as a motor time) and cognitive processing (measured as a reaction time). Mini‐Mental State Examination (MMSE) was used to measure the severity of cognitive impairment (mean score: 26.20±2.44). Correlation analysis was used to analyze the liner relationship between the average LPP amplitude in the occipital areas (Oz, O1, and O2; time window: 400 to 800 ms after stimulus presentation), reaction time on the three versions of the VRTT, and reaction time on the SVT.ResultWe found significant correlations between reaction time on the SVT and motor time on VRTT (S1: p = 0.015; S2: p = 0.075; S3: p = 0.021;), but we found no significant correlations between reaction time on the SVT and VRTT (ps > 0.193), no significant correlations between LPP amplitude in the occipital areas and reaction time on any of the tasks (SVT: p > 0.056, VRTT: ps > 0.288) or between LPP amplitude and motor time on any version of the VRTT (ps > 0.500).ConclusionOur preliminary results indicate that LPP amplitude measured over the occipital area was not significantly associated with sustained attention or inhibition.

The difference between induced insight by hints and induced insight by answers: an event-related potential study.

We can solve insight problems by ourselves, by hints or by answers. This study compared the temporal features of different types of insight (spontaneous insight, induced insight by hints and induced insight by answers). Fifteen college students participated in the Chinese Remote Association Task. If they did not come up with an answer, the cue word was presented. Finally, they needed to judge whether the answer was correct or not. Participants' brain electroencephalography-event-related potentials (ERPs) were recorded. Induced insight by hints elicited a more negative ERP deflection than spontaneous insight within 260-400 ms (N2). Induced insight by hints and induced insight by answers elicited a more negative late negative component (LNC) than spontaneous insight. Induced insight by hints elicited a more positive ERP deflection than induced insight by answers and spontaneous insight in the right frontal area. Spontaneous insight and induced insight by answers elicited a more positive ERP deflection than induced insight by hints in the right part of the central region. When solving insight problems, the N2 may be related to representation restructuring. The first LNC may be related to the breaking of mental set. The positive component of the right frontal area before pressing the button may be related to the formation of novel associations, and the positive component of the right part of the central region may be related to the intensity of the 'Aha!' experience.

The Reward-Related Shift of Emotional Contagion from the Observer's Perspective Correlates to Their Intimacy with the Expresser.

Although previous studies have found a bidirectional relationship between emotional contagion and reward, there is insufficient research to prove the effect of reward on the social function of emotional contagion. To explore this issue, the current study used electroencephalography (EEG) and the interactive way in which the expresser played games to help participants obtain reward outcomes. The results demonstrated a significant correlation between changes in emotional contagion and closeness, indicating that emotional contagion has a social regulatory function. Regarding the impact of reward outcomes, the results showed that compared to the context of a loss, in the context of a win, participants' closeness toward the expresser shifted to a more intimate level, their emotional contagion changed in a more positive direction, and the activity of the late positive component (LPC) of the event-related potentials (ERPs) changed to a greater extent. Significantly, the mediation results demonstrated the effect of reward and indicated that changes in the LPC elicited while experiencing the expressers' emotion predicted the subsequent shifts in closeness through alterations in emotional contagion of the anger emotion in the winning context and the happy emotion in the loss context. This study provides empirical evidence regarding the social function of emotional contagion and proves for the first time that the reward context plays a role in it.

PSIX-9 Activation of Multiple Inflammatory Signaling Pathways May Contribute to the Pathogenesis of Idiopathic Cystitis in Felines

Abstract Feline idiopathic cystitis (FIC) is a common urinary disorder in domestic cats. Clinical signs include straining or failing to urinate, frequent urination, and discolored urine. Inflammation is a key characteristic in the pathogenesis of cystitis. We assessed circulating inflammatory markers in a retrospective study in cats housed in the Hill’s colony diagnosed with cystitis (n = 4; 15.2 to 18.6yr) and in control cats (n = 8; 5.9 to 16.5 yr). Blood samples were collected at end-of-life immediately before necropsy after they had lived their full lives. End-of-life pathology reports indicated inflammation and presence of inflammatory infiltrates in the bladder with some cats also showing renal inflammation. RNA was extracted from blood collected in PAXgene tubes, and gene expression investigated using NanoString nCounter platform. Analysis was performed using the nSolver software. There was a significant increase in IRAK4, a kinase that activates the NFκB pro-inflammatory signaling pathway, in FIC when compared with controls (1.56, P < 0.05). Small molecule inhibitors of IRAK4 are being developed as targets of inflammation. Signaling molecules in the NFκB pathway were also significantly increased including Rel A (p65 subunit; 1.3 fold), NFκB1 (p100 subunit; 1.3 fold), IKBKB (1.29 fold), and TANK (1.46 fold) in FIC cats (all P < 0.05). Another signaling pathway contributing to pro-inflammatory signaling is the JAK/STAT pathway. There was a significant increase in JAK2 (1.65) and STAT3 (1.48). Blockade of JAK2/STAT3 pathway can attenuate cytokine synthesis and reduce inflammation. STAT6 was also significantly increased in FIC cats (1.35). Activation of STAT6, by IL-4 and IL-13, can lead to systemic inflammation. Activation of the complement immune pathway was also seen in FIC. While the complement system is important for an innate immune response, its sustained activation leads to chronic pathological inflammation. There was a significant increase in complement C1s, an initiator of classical complement activation pathway, in FIC cats (1.43; P < 0.05). A late component, complement C7, was also upregulated in FIC (2.01 fold; P < 0.05). C7 binds to the C5b-6 complex which eventually becomes part of the terminal complement complex. Increased abundance of C7 and eventual terminal complement complex are associated with increased inflammation and may be important in the progression of FIC. There was also an increase in PECAM1 in FIC cats (1.87; P < 0.05). Signaling through PECAM1 leads to the activation of neutrophils and monocytes. DUSP1 was also elevated in FIC (2.24; P < 0.05). Increased abundance of DUSP1 is hypothesized to be a predictor of chronic subclinical inflammation in humans with cardiovascular disease. Our results identify activation of pro-inflammatory signaling pathways that may be potential targets for alleviating inflammation in cystitis. Pathogenesis of FIC is likely multi-factorial, and nutritional intervention to attenuate the activation of inflammatory pathways may be an important strategy in the management of cystitis.

The Effect of Accelerated Continuous Theta Burst Stimulation on Weight Loss in Overweight Individuals With Schizophrenia: A Double-Blind, Randomized, Sham-Controlled Clinical Trial.

Obesity is a common comorbidity in individuals with schizophrenia and is associated with poor clinical outcomes. At present, there are limited effective approaches for addressing this issue. We conducted a double-blind, randomized, sham-controlled clinical trial to investigate the efficacy of noninvasive magnetic stimulation techniques in reducing obesity in individuals with schizophrenia. Forty overweight individuals with schizophrenia were recruited and randomly assigned to receive either the active or sham intervention. The active group received 50 accelerated continuous theta burst stimulation (cTBS) sessions over the left primary motor area (M1), while the sham group received sham stimulation. The primary outcomes were the change in body weight and body mass index (BMI), and the secondary outcomes were the psychiatric symptoms, eating behavior scales, metabolic measures, and electrophysiological to food picture stimuli. The study demonstrated a significant decrease in body weight and BMI after the intervention selectively in the active group (mean = -1.33 kg, P = .002), and this improvement remained at the 1-month follow-up (mean = -2.02 kg, P = .008). The score on the Barratt Impulsivity Scale (mean = -1.78, P = 0.036) decreased in the active group and mediated the effect of accelerated cTBS on body weight. In the food picture cue electroencephalograph task, the late positive potential component, which is related to motivated attention and emotional processing, decreased in frontal brain regions and increased in posterior regions after the active intervention. The accelerated cTBS may offer a promising approach for treating obesity in individuals with schizophrenia. Further research with a larger sample size or individualized stimulation protocol should be promising. Clinical trial registered with clinicaltrials.gov (NCT05086133).

Effect of presentation rate on auditory processing in Rett syndrome: event-related potential study

BackgroundRett syndrome (RS) is a rare neurodevelopmental disorder characterized by mutations in the MECP2 gene. Patients with RS have severe motor abnormalities and are often unable to walk, use hands and speak. The preservation of perceptual and cognitive functions is hard to assess, while clinicians and care-givers point out that these patients need more time to process information than typically developing peers. Neurophysiological correlates of auditory processing have been also found to be distorted in RS, but sound presentation rates were relatively quick in these studies (stimulus onset asynchrony, SOA < 1000 ms). As auditory event-related potential (ERP) is typically increased with prolongation of SOA we aim to study if SOA prolongation might compensate for observed abnormalities.MethodsWe presented a repetitive stimulus (1000 Hz) at three different SOAs of 900 ms, 1800 ms, and 3600 ms in children with RS (N = 24, Mean age = 9.0 ± 3.1) and their typical development (TD) peers (N = 27, Mean age = 9.7 ± 3.4) while recording 28-channels electroencephalogram, EEG. Some RS participants (n = 10) did not show clear ERP and were excluded from the analysis.ResultsMajor ERP components (here assessed as N1P1 and P2N1 peak-to-peak values) were smaller at SOA 900 than at longer SOAs in both groups, pointing out that the basic mechanism of adaptation in the auditory system is preserved in at least in RS patients with evident ERPs. At the same time the latencies of these components were significantly delayed in the RS than in TD. Moreover, late components (P2N1 and N2P2) were drastically reduced in Rett syndrome irrespective of the SOA, suggesting a largely affected mechanism of integration of upcoming sensory input with memory. Moreover, developmental stagnation of auditory ERP characterized patients with RS: absence of typical P2N1 enlargement and P1 and N1 shortening with age at least for shortest SOA.LimitationsWe could not figure out the cause for the high percentage of no-evident ERP RS participants and our final sample of the RS group was rather small. Also, our study did not include a control clinical group.ConclusionsThus, auditory ERPs inform us about abnormalities within auditory processing that cannot be fully overcomed by slowing presentation rate.

Alterations of auditory sensory gating in mice with noise-induced tinnitus treated with nicotine and cannabis extract.

Tinnitus is a phantom sound perception affecting both auditory and limbic structures. The mechanisms of tinnitus remain unclear and it is debatable whether tinnitus alters attention to sound and the ability to inhibit repetitive sounds, a phenomenon also known as auditory gating. Here we investigate if noise exposure interferes with auditory gating and whether natural extracts of cannabis or nicotine could improve auditory pre-attentional processing in noise-exposed mice. We used 22 male C57BL/6J mice divided into noise-exposed (exposed to a 9-11 kHz narrow band noise for 1 h) and sham (no sound during noise exposure) groups. Hearing thresholds were measured using auditory brainstem responses, and tinnitus-like behavior was assessed using Gap prepulse inhibition of acoustic startle. After noise exposure, mice were implanted with multi-electrodes in the dorsal hippocampus to assess auditory event-related potentials in response to paired clicks. The results showed that mice with tinnitus-like behavior displayed auditory gating of repetitive clicks, but with larger amplitudes and longer latencies of the N40 component of the aERP waveform. The combination of cannabis extract and nicotine improved the auditory gating ratio in noise-exposed mice without permanent hearing threshold shifts. Lastly, the longer latency of the N40 component appears due to an increased sensitivity to cannabis extract in noise-exposed mice compared to sham mice. The study suggests that the altered central plasticity in tinnitus is more sensitive to the combined actions on the cholinergic and the endocannabinoid systems. Overall, the findings contribute to a better understanding of pharmacological modulation of auditory sensory gating.

The role of multifocal electroretinography in the preclinical diagnosis of tumor-associated distant maculopathy in small melanoma of the choroid of extramacular localization

To assess the role of multifocal electroretinography (mf-ERG) in preclinical diagnosis of tumor-associated distant maculopathy in small choroidal melanoma (CM) of extramacular localization.Material and methods. 35 patients (35 affected and 35 fellow eyes) with small CM of extramacular localization and 23 healthy volunteers (46 eyes) aged 59.67 ± 14.2 years were given general ophthalmological examinations and mf-ERG. Density (nV/deg2), culmination time of the P1 component and amplitude (μV) of the N1 component were measured for 5 response rings (R1–R5) at different distances from the fixation point: central hexagon R1: 2.3° (fovea zone); R2: 2.3–6.9° (parafovea); R3: 6.9–14.3° (perifovea); R4: 14.3–20.8° and R5: 20.8–29.9° (middle periphery areas of the retina).Results. Eyes affected by CM showed a decrease in the density of the P1 component in the R1 hexagon by 25.7% of the normal values (p = 0.03). The fellow eyes showed an increase in the density of the P1 component in the R2 ring (p &lt; 0.05). The peak latency of the P1 component in the R1–R5 rings in the affected and fellow eye was found to elongate by 30–45% (p &lt; 0.05). The amplitude of the N1 component in the central hexagon of CM-affected eyes increased by 12.96%, whilst in the R4–R5 rings it decreased by 36–45% as compared with healthy individuals (p &lt; 0.05). The fellow eye showed supernormal values of the N1 amplitude in R1 and its suppression in R4 and R5 rings (p &lt; 0.05).Conclusion. The mf-ERG method is useful for preclinical diagnosis of tumor-associated distant maculopathy in small CM of extramacular localization. Changes in mf-ERG of the fellow eye in patients with small CM have been documented.

Amplification Effects on the Acoustic Change Complex in Older Adults With Sensorineural Hearing Loss

Purpose: This pilot study evaluated the effect of stimulus level and amplification on the acoustic change complex (ACC) in adults with sensorineural hearing loss. Method: Ten adults with a M age of 74 years and bilaterally symmetrical mild-to-severe sensorineural hearing loss listened to contrasting vowel pairs, while cortical evoked potentials were recorded. The vowel contrasts (/a/−/i/ and /u/−/o/) were presented in the sound field at 30 and 60 dBA. Participants were tested with and without amplification fit to their audiogram configurations. ACC component P1–N1–P2 latencies and P1–N1, N1–P2, and P2–N2 peak-to-trough amplitudes were measured for eight test conditions ([two vowel contrasts] × [two levels] × [aided vs. unaided]). Paired-sample t tests were used to determine the effects of test conditions on ACC component latencies and amplitudes. Results: At 60 dBA, nine of 10 listeners had ACCs in the unaided condition, and the ACC amplitudes were significantly increased in the aided condition for the /a/−/i/ contrast. Amplification did not affect ACC amplitudes for the /u/−/o/ contrast at 60 dBA. At 30 dBA, only three of 10 participants had ACCs present in the aided condition, and none had ACCs in the unaided condition. ACC latencies at 60 dBA were unaffected as a function of amplification, but differences were noted as a function of vowel contrast type. Conclusions: ACCs were obtained for adults with hearing loss, demonstrating the feasibility of measuring a listener's neural capacity to discriminate vowel contrasts. The data indicate promising efficacy for using the ACC to evaluate those who cannot provide reliable perceptual responses, such as in immaturity (infants) or neurocognitive conditions (dementia). The ACC provides evidence of the sensory and neural capacity to detect and discriminate vowel sound contrasts, a neuro-biological validation that can be coupled with electroacoustic verification.

Adaptation of the late ISC pathway in the anaerobic mitochondrial organelles of Giardia intestinalis.

Mitochondrial metabolism is entirely dependent on the biosynthesis of the [4Fe-4S] clusters, which are part of the subunits of the respiratory chain. The mitochondrial late ISC pathway mediates the formation of these clusters from simpler [2Fe-2S] molecules and transfers them to client proteins. Here, we characterized the late ISC pathway in one of the simplest mitochondria, mitosomes, of the anaerobic protist Giardia intestinalis that lost the respiratory chain and other hallmarks of mitochondria. In addition to IscA2, Nfu1 and Grx5 we identified a novel BolA1 homologue in G. intestinalis mitosomes. It specifically interacts with Grx5 and according to the high-affinity pulldown also with other core mitosomal components. Using CRISPR/Cas9 we were able to establish full bolA1 knock out, the first cell line lacking a mitosomal protein. Despite the ISC pathway being the only metabolic role of the mitosome no significant changes in the mitosome biology could be observed as neither the number of the mitosomes or their capability to form [2Fe-2S] clusters in vitro was affected. We failed to identify natural client proteins that would require the [2Fe-2S] or [4Fe-4S] cluster within the mitosomes, with the exception of [2Fe-2S] ferredoxin, which is itself part of the ISC pathway. The overall uptake of iron into the cellular proteins remained unchanged as also observed for the grx5 knock out cell line. The pull-downs of all late ISC components were used to build the interactome of the pathway showing specific position of IscA2 due to its interaction with the outer mitosomal membrane proteins. Finally, the comparative analysis across Metamonada species suggested that the adaptation of the late ISC pathway identified in G. intestinalis occurred early in the evolution of this supergroup of eukaryotes.

Effects of reversible SERCA inhibition on catecholamine exocytosis and intracellular [Ca2+] signaling in chromaffin cells from normotensive Wistar Kyoto rats and spontaneously hypertensive rats

Intracellular Ca2+ ([Ca2+]i) signaling and catecholamine (CA) exocytosis from adrenal chromaffin cells (CCs) differ between mammalian species. These differences partly result from the different contributions of Ca2+-induced Ca2+-release (CICR) from internal stores, which boosts intracellular Ca2+ signals. Transient inhibition of the sarcoendoplasmic reticulum (SERCA) Ca2+ pump with cyclopiazonic acid (CPA) reduces CICR. Recently, Martínez-Ramírez et al. found that CPA had contrasting effects on catecholamine secretion and intracellular Ca2+ signals in mouse and bovine CCs, where it enhanced and inhibited exocytosis, respectively. After CPA withdrawal, exocytosis diminished in mouse CCs and increased in bovine CCs. These differences can be explained if mouse CCs have weak CICR and strong Ca2+ uptake, and the reverse is true for bovine CCs. Surprisingly, CPA slightly reduced the amplitude of Ca2+ signals in both mouse and bovine CCs. Here we examined the effects of CPA on stimulated CA exocytosis and Ca2+ signaling in rat CCs and investigated if it alters differently the responses of CCs from normotensive (WKY) or hypertensive (SHR) rats, which differ in the gain of CICR. Our results demonstrate that CPA application strongly inhibits voltage-gated exocytosis and Ca2+ transients in rat CCs, regardless of strain (SHR or WKY). Thus, despite the greater phylogenetic distance from the most recent common ancestors, suppression of endoplasmic reticulum (ER) Ca2+ uptake through CPA inhibits the CA secretion in rat CCs more similarly to bovine than mouse CCs, unveiling divergent evolutionary relationships in the mechanism of CA exocytosis of CCs between rodents. Agents that inhibit the SERCA pump, such as CPA, suppress catecholamine secretion equally well in WKY and SHR CCs and are not potential therapeutic agents for hypertension. Rat CCs display Ca2+ signals of varying widths. Some even show early and late Ca2+ components. Narrowing the Ca2+ transients by CPA and ryanodine suggests that the late component is mainly due to CICR. Simultaneous recordings of Ca2+ signaling and amperometry in CCs revealed the existence of a robust and predictable correlation between the kinetics of the whole-cell intracellular Ca2+ signal and the rate of exocytosis at the single-cell level.

Petrology and geochemistry of Late Triassic rapakivi-type granites in the Dupangling area, South China: Role of fluid-rock interaction in the origin of rapakivi texture

Rapakivi-type granites not only document magmatic processes but also archive subsolidus interactions between granitic rock and fluid, and thereby provide crucial information about fluid infiltration in the Earth's crust. However, the key process to generate rapakivi texture is still debated. Here, we report comprehensive mineralogical, geochemical and Hf isotopic compositions of the Dupangling rapakivi granites (210.4–214.9 Ma) in the South China Block to investigate the effect of fluid-rock interaction on the origin of rapakivi feldspar. Dupangling rapakivi granites have high SiO2 (72.63–78.21 wt%) and alkali contents (Na2O + K2O = 6.14–9.06 wt%) with high K2O/Na2O ratios (1.37–2.64), characteristic of weakly peraluminous (A/CNK = 1.04–1.10) high-K calc-alkaline granites. Samples have weakly fractionated REE patterns with negative Eu anomalies (δEu = 0.05–0.38). They have negative whole-rock εNd(t) (−8.45 to −7.91), variable zircon εHf(t) (−9.7 to −1.0) and two-stage Hf isotope model ages (1.32–1.84 Ga), due to their derivation from a major early Mesoproterozoic crustal source with a subordinate late Paleoproterozoic component. Rapakivi feldspars in Dupangling granites are composed of an alkali-feldspar core and a plagioclase mantle. Fractures, pores and secondary inclusions (biotite, sericite, epidote and hematite) are closely associated with the mantles and oligoclase patches within alkali-feldspar cores. These pervasive microtextural features and variations of Be, Rb, Ba, Sr and LREE within rapakivi feldspars are interpreted to have formed through subsolidus fluid-induced dissolution-reprecipitation replacement processes. This study highlights that fluid-rock interaction plays an important role in generating rapakivi texture.

Investigating the Impact of Selective Modulators on the Renin-Angiotensin-Aldosterone System: Unraveling Their Off-Target Perturbations of Transmembrane Ionic Currents.

The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in maintaining various physiological processes in the body, including blood pressure regulation, electrolyte balance, and overall cardiovascular health. However, any compounds or drugs known to perturb the RAAS might have an additional impact on transmembrane ionic currents. In this retrospective review article, we aimed to present a selection of chemical compounds or medications that have long been recognized as interfering with the RAAS. It is noteworthy that these substances may also exhibit regulatory effects in different types of ionic currents. Apocynin, known to attenuate the angiotensin II-induced activation of epithelial Na+ channels, was shown to stimulate peak and late components of voltage-gated Na+ current (INa). Esaxerenone, an antagonist of the mineralocorticoid receptor, can exert an inhibitory effect on peak and late INa directly. Dexamethasone, a synthetic glucocorticoid, can directly enhance the open probability of large-conductance Ca2+-activated K+ channels. Sparsentan, a dual-acting antagonist of the angiotensin II receptor and endothelin type A receptors, was found to suppress the amplitude of peak and late INa effectively. However, telmisartan, a blocker of the angiotensin II receptor, was effective in stimulating the peak and late INa along with a slowing of the inactivation time course of the current. However, telmisartan's presence can also suppress the erg-mediated K+ current. Moreover, tolvaptan, recognized as an aquaretic agent that can block the vasopressin receptor, was noted to suppress the amplitude of the delayed-rectifier K+ current and the M-type K+ current directly. The above results indicate that these substances not only have an interference effect on the RAAS but also exert regulatory effects on different types of ionic currents. Therefore, to determine their mechanisms of action, it is necessary to gain a deeper understanding.

Lifespan variation among people with a given disease or condition.

In addition to fundamental mortality metrics such as mortality rates and mortality rate ratios, life expectancy is also commonly used to investigate excess mortality among a group of individuals diagnosed with specific diseases or conditions. However, as an average measure, life expectancy ignores the heterogeneity in lifespan. Interestingly, the variation in lifespan-a measure commonly used in the field of demography-has not been estimated for people with a specific condition. Based on recent advances in methodology in research within epidemiology and demography, we discuss two metrics, namely, the average life disparity and average lifetable entropy after diagnosis, which estimate the variation in lifespan for time-varying conditions in both absolute and relative aspects. These metrics are further decomposed into early and late components, separated by their threshold ages. We use mortality data for women with mental disorders from Danish registers to design a population-based study and measure such metrics. Compared with women from the general population, women with a mental disorder had a shorter average remaining life expectancy after diagnosis (37.6 years vs. 44.9 years). In addition, women with mental disorders also experienced a larger average lifespan variation, illustrated by larger average life disparity (9.5 years vs 9.1 years) and larger average lifetable entropy (0.33 vs 0.27). More specifically, we found that women with a mental disorder had a larger early average life disparity but a smaller late average life disparity. Unlike the average life disparity, both early and late average lifetable entropy were higher for women with mental disorders compared to the general population. In conclusion, the metric proposed in our study complements the current research focusing merely on life expectancy and further provides a new perspective into the assessment of people's health associated with time-varying conditions.