A mathematical framework for measuring and tuning tempo in developmental gene regulatory networks.

Embryo development is a dynamic process governed by the regulation of timing and sequences of gene expression, which control the proper growth of the organism. Although many genetic programmes coordinating these sequences are common across species, the timescales of gene expression can vary significantly among different organisms. Currently, substantial experimental efforts are focused on identifying molecular mechanisms that control these temporal aspects. In contrast, the capacity of established mathematical models to incorporate tempo control while maintaining the same dynamical landscape remains less understood. Here, we address this gap by developing a mathematical framework that links the functionality of developmental programmes to the corresponding gene expression orbits (or landscapes). This unlocks the ability to find tempo differences as perturbations in the dynamical system that preserve its orbits. We demonstrate that this framework allows for the prediction of molecular mechanisms governing tempo, through both numerical and analytical methods. Our exploration includes two case studies: a generic network featuring coupled production and degradation, with a particular application to neural progenitor differentiation; and the repressilator. In the latter, we illustrate how altering the dimerisation rates of transcription factors can decouple the tempo from the shape of the resulting orbits. We conclude by highlighting how the identification of orthogonal molecular mechanisms for tempo control can inform the design of circuits with specific orbits and tempos.

Neurovascular dysfunction associated with erectile dysfunction persists after long-term recovery from simulations of weightlessness and deep space irradiation.

There has been growing interest within the space industry for long-duration manned expeditions to the Moon and Mars. During deep space missions, astronauts are exposed to high levels of galactic cosmic radiation (GCR) and microgravity which are associated with increased risk of oxidative stress and endothelial dysfunction. Oxidative stress and endothelial dysfunction are causative factors in the pathogenesis of erectile dysfunction, although the effects of spaceflight on erectile function have been unexplored. Therefore, the purpose of this study was to investigate the effects of simulated spaceflight and long-term recovery on tissues critical for erectile function, the distal internal pudendal artery (dIPA), and the corpus cavernosum (CC). Eighty-six adult male Fisher-344 rats were randomized into six groups and exposed to 4-weeks of hindlimb unloading (HLU) or weight-bearing control, and sham (0Gy), 0.75 Gy, or 1.5 Gy of simulated GCR at the ground-based GCR simulator at the NASA Space Radiation Laboratory. Following a 12-13-month recovery, ex vivo physiological analysis of the dIPA and CC tissue segments revealed differential impacts of HLU and GCR on endothelium-dependent and -independent relaxation that was tissue type specific. GCR impaired non-adrenergic non-cholinergic (NANC) nerve-mediated relaxation in the dIPA and CC, while follow-up experiments of the CC showed restoration of NANC-mediated relaxation of GCR tissues following acute incubation with the antioxidants mito-TEMPO and TEMPOL, as well as inhibitors of xanthine oxidase and arginase. These findings indicate that simulated spaceflight exerts a long-term impairment of neurovascular erectile function, which exposes a new health risk to consider with deep space exploration.

A Computational Analysis of the Proton Affinity and the Hydration of TEMPO and Its Piperidine Analogs.

The study investigated the impact of protonation and hydration on the geometry of nitroxide radicals using B3LYP and M06-2X methods. Results indicated that TEMPO exhibited the highest proton affinity in comparison to TEMPOL and TEMPONE. Two pathways contribute to hydrated protonated molecules. TEMPO shows lower first enthalpies of hydration (ΔH1-M), indicating stronger H-bonding interactions, while TEMPONE shows higher values, indicating weaker interactions with H2O. Solvent effects affect charge distribution by decreasing their atomic charge. Spin density (SD) is primarily concentrated in the NO segment, with minimal water molecule contamination. Protonation increases SD on N-atom, while hydration causes a more pronounced redistribution for water molecules. The stability of the dipolar structure (>N⋅+-O-) is evident in SD redistributions. The frontier molecular orbital (FMO) analysis of TEMPONE reveals a minimum EHOMO-LUMO gap (EH-L), enhancing the piperidine ring's reactivity. TEMPO is the most nucleophilic species, while TEMPONE exhibits strong electrophilicity. Transitioning from NO radicals to protonated forms increases the EH-L gap, indicating protonation stabilizes FMOs. Increased water molecules make the molecule less reactive, while increasing hydration decreases this energy gap, making the molecule more reactive. A smaller EH-L gap indicates the compound becomes softer and more prone to electron density and reactivity changes.

Clinical distinction between cognitive disengagement syndrome and ADHD presentations in a nationally representative sample of Spanish children and adolescents.

BACKGROUND: This study sought to determine whether cognitive disengagement syndrome (CDS, formerly sluggish cognitive tempo) has different external correlates relative to ADHD-inattentive presentation (INP), ADHD-hyperactive/impulsive presentation (HIP), and ADHD-combined presentation (CP). METHODS: Parents of a nationally representative sample of 5,525 Spanish youth (ages: 5-16, 56.1% boys) completed measures of CDS, ADHD-inattention (IN), and ADHD-hyperactivity/impulsivity (HI) and other measures. Scores greater/less than the top 5% on CDS, ADHD-IN, and ADHD-HI were used to create control (n = 5,013, 90.73%), CDS-only (n = 131, 2.37%), ADHD-INP-only (n = 83, 1.50%), ADHD-HIP-only (n = 113, 2.05%), ADHD-CP-only (n = 48, 0.97%), CDS + ADHD-INP (n = 44, 0.80%), CDS + ADHD-HIP (n = 25, 0.45%), and CDS + ADHD-CP (n = 68, 1.23%) groups. RESULTS: Forty-nine percent of youth with clinically elevated CDS did not qualify for any ADHD presentation, whereas 64% of youth with clinically elevated ADHD did not qualify for CDS. The CDS-only group was higher than the ADHD-INP-only, ADHD-HIP-only, and ADHD-CP-only groups on anxiety, depression, somatization, daytime sleep-related impairment, nighttime sleep disturbance, and peer withdrawal, whereas the CDS-only and ADHD-INP-only groups did not differ on ODD (ADHD-HIP-only and ADHD-CP-only higher) and academic impairment (ADHD-CP-only higher than CDS-only and ADHD-HIP-only lower than CDS-only). The CDS-only group also had higher rates of anxiety, depression, and bipolar disorder diagnoses than the ADHD-only group. CONCLUSIONS: A distinction was found between CDS and each ADHD presentation, thus providing support for CDS as a syndrome that frequently co-occurs with yet is distinct from each ADHD presentation.

Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

Interdependence of movement amplitude and tempo during self-paced finger tapping: evaluation of a preferred velocity hypothesis.

This study examined the relation between movement amplitude and tempo during self-paced rhythmic finger tapping to test a preferred velocity account of the preferred tempo construct. Preferred tempo refers to the concept that individuals have preferences for the pace of actions or events in their environment (e.g., the desired pace of walking or tempo of music). The preferred velocity hypothesis proposes that assessments of preferred tempo do not represent a pure time preference independent of spatial movement characteristics, but rather reflects a preference for an average movement velocity, predicting that preferred tempo will depend on movement amplitude. We tested this by having participants first perform a novel spontaneous motor amplitude (SMA) task in which they repetitively tapped their finger at their preferred amplitude without instructions about tapping tempo. Next, participants completed the spontaneous motor tempo (SMT) task in which they tapped their finger at their preferred tempo without instructions about tapping amplitude. Finally, participants completed a target amplitude version of the SMT task where they tapped at their preferred tempo at three target amplitudes (low, medium, and high). Participants (1) produced similar amplitudes and tempi regardless of instructions to produce either their preferred amplitude or preferred tempo, maintaining the same average movement velocity across SMA and SMT tasks and (2) altered their preferred tempo for different target amplitudes in the direction predicted by their estimated preferred velocity from the SMA and SMT tasks. Overall, results show the interdependence of movement amplitude and tempo in tapping assessments of preferred tempo.

Fluorescence Quenching Effect of a Highly Active Nitroxyl Radical on 7-amino-4-methylcoumarin and Glutathione Sensing.

Nitroxyl radical compounds, such as 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), are stable radical compounds with a variety of unique characteristics, including fluorescence quenching. In this study, we investigated the fluorescence quenching effect of nortropine N-oxyl (NNO), which is a highly active nitroxyl radical that is more active than TEMPO in oxidation catalysis. The fluorescence intensity of 7-amino-4-methylcoumarin (AMC) was quenched by NNO and TEMPO to 5% and 95% of the initial fluorescence intensity, respectively, indicating highly efficient quenching by NNO. In addition, we used this reaction to measure glutathione concentration. The quenching effect of NNO was abrogated by the chemical reaction with glutathione, resulting in restoration of AMC fluorescence. This response was observed at glutathione concentrations from 10 µM to 1 mM, and good calibration curves were obtained from 10 to 250 µM.

Characterization of TEMPO-Oxidized Cellulose Nanofiber From Biowaste and Its Influence on Molecular Behavior of Fluorescent Rhodamine B Dye in Aqueous Suspensions.

Cellulose nanofiber (CNFs) obtained through TEMPO oxidation was structurally characterized using FT-IR (Fourier Transformed Infrared) and SEM (Scanning Electron Microscopy) spectroscopy. The molecular aggregation and spectroscopic properties of Rhodamine B (Rh-B) in CNFs suspension were investigated using molecular absorption and steady-state fluorescence spectroscopy techniques. The interaction between CNFs particles in the aqueous suspension and the cationic dye compound was examined in comparison to its behavior in deionized water. This interaction led to significant changes in the spectral features of Rh-B, resulting in an increase in the presence of H-dimer and H-aggregate in CNFs suspension. The H-type aggregates of Rh-B in CNFs suspensions were defined by the observation of a blue-shifted absorption band compared to that of the monomer. Even at diluted dye concentrations, the formation of Rh-B's H-aggregate was observed in CNFs suspension. The pronounced aggregation in suspensions originated from the strong interaction between negatively charged carboxylate ions and the dye. The aggregation behavior was discussed with deconvoluted absorption spectra. Fluorescence spectroscopy studies revealed a significant reduction in the fluorescence intensity of the dye in CNFs suspension due to H-aggregates. Furthermore, the presence of H-aggregates in the suspensions caused a decrease in the quantum yield of Rh-B compared to that in deionized water.

Harmonizing Energies: The Interplay Between a Nonplanar SalEn-Type Molecule and a TEMPO Moiety in a New Hybrid Energy-Storing Redox-Conducting Polymer.

Redox-conducting polymers based on SalEn-type complexes have attracted considerable attention due to their potential applications in electrochemical devices. However, their charge transfer mechanisms, physical and electrochemical properties remain unclear, hindering their rational design and optimization. This study aims to establish the influence of monomer geometry on the polymer's properties by investigating the properties of novel nonplanar SalEn-type complexes, poly[N,N'-bis(salicylidene)propylene-2-(hydroxy)diaminonickel(II)], and its analog with 2,2,6,6-tetramethylpiperidinyl-N-oxyl (TEMPO)-substituted bridge (MTS). To elucidate the charge transfer mechanism, operando UV-Vis spectroelectrochemical analysis, electrochemical impedance spectroscopy, and electron paramagnetic resonance are employed. Introducing TEMPO into the bridge moiety enhanced the specific capacity of the poly(MTS) material to 95 mA h g-1, attributed to TEMPO's and conductive backbone's charge storage capabilities. Replacement of the ethylenediimino-bridge with a 1,3-propylenediimino- bridge induced significant changes in the complex geometry and material's morphology, electrochemical, and spectral properties. At nearly the same potential, polaron and bipolaron particles emerged, suggesting intriguing features at the overlap point of the electroactivity potentials ranges of polaron-bipolaron and TEMPO, such as a disruption in the connection between TEMPO and the conjugation chain or intramolecular charge transfer. These results offer valuable insights for optimizing strategies to create organic materials with tailored properties for use in catalysis and battery applications.

Mito-Tempo alleviates ox-LDL-provoked foam cell formation by regulating Nrf2/NLRP3 signaling.

Our previous studies have demonstrated that Mito-Tempol (also known as 4-hydroxy-Tempo), a mitochondrial reactive oxygen species scavenger, alleviates oxidized low-density lipoprotein (ox-LDL)-triggered foam cell formation. Given the effect of oxidative stress on activating the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome, which promotes foam cell formation, we aimed to explore whether Mito-Tempo inhibits ox-LDL-triggered foam cell formation by regulating NLRP3 inflammasome. The results revealed that Mito-Tempo re-activated Nrf2 and alleviated macrophage foam cell formation induced by ox-LDL, whereas the effects were reversed by ML385 (a specific Nrf2 inhibitor). Mito-Tempo restored the expression and nuclear translocation of Nrf2 by decreasing ox-LDL-induced ubiquitination. Furthermore, Mito-Tempo suppressed ox-LDL-triggered NLRP3 inflammasome activation and subsequent pyroptosis, whereas the changes were blocked by ML385. Mito-Tempo decreased lipoprotein uptake by inhibiting CD36 expression and suppressed foam cell formation by regulating the NLRP3 inflammasome. Taken together, Mito-Tempo exhibits potent anti-atherosclerotic effects by regulating Nrf2/NLRP3 signaling.

The effect of the mitochondria-targeted antioxidant Mito-tempo during sperm ultra-rapid freezing.

During the freeze-thaw process, human spermatozoa are susceptible to oxidative stress, which may cause cryodamage and reduce sperm quality. As a novel mitochondria-targeted antioxidant, Mito-tempo has been used for sperm cryopreservation. However, it is currently unknown what role it will play in the process of sperm ultra-rapid freezing. The purpose of this study was to investigate whether Mito-tempo can improve sperm quality during ultra-rapid freezing. In this study, samples with the addition of Mito-tempo (0, 5, 10, 20, and 40 µM) to sperm freezing medium were selected to evaluate the changes in sperm quality, antioxidant capacity and ultrastructure after ultra-rapid freezing. After ultra-rapid freezing, the quality and antioxidant function of the spermatozoa were significantly reduced and the spermatozoa ultrastructure was destroyed. The addition of 10 µM Mito-tempo significantly increased post thaw sperm motility, viability, plasma membrane integrity and mitochondrial membrane potential (P < 0.05). Moreover, the DNA fragmentation index (DFI), ROS levels and MDA content were reduced, and the antioxidant enzyme (CAT and SOD) activities were enhanced in the 10 µM Mito-tempo group (P < 0.05). Moreover, Mito-tempo protected sperm ultrastructure from damage. In conclusion, Mito-tempo improved the quality and antioxidant function of sperm after ultra-rapid freezing while reducing freezing-induced ultrastructural damage.

Exploring the accuracy of musical tempo memory: The effects of reproduction method, reference tempo, and musical expertise.

Although people commonly remember and recreate the tempo of musical pieces with high accuracy, comparatively less is known regarding sources of potential variation in musical tempo memory. This study therefore aimed to investigate musical tempo memory accuracy and the effects of reference tempo, reproduction method, musical expertise, and their interaction. A sample of 403 individuals with varying levels of musical training participated in the experimental online study, including nonmusicians, amateur musicians, and professional musicians. Participants were tasked with reproducing the tempos of 19 popular pop/rock songs using two methods: tempo tapping and adjusting the tempo of the audio file based on the previously tapped tempo. Results from multilevel models revealed overall high accuracy in tempo memory, with tempo adjusting yielding greater accuracy compared with tempo tapping. Higher musical expertise was associated with increased accuracy in tempo production. In addition, we observed a quadratic effect of reference tempo, with the greatest accuracy in tempo reproduction around 120 bpm. Gender, age, familiarity with the pieces, and accompaniment strategies were also associated with greater accuracy. These findings provide insights into the factors influencing musical tempo memory and have implications for understanding the cognitive processes involved in tempo perception and reproduction.

Biophysical Modelling for Insight into Oxygen Diffusion, Distribution, and Measurement.

Building on an extensive history of physiological and systems-oriented modelling, my group and others have recently used molecular simulation studies to understand oxygen (O2) transport and localisation. Molecular simulations enable biophysical insight into processes difficult to study with experiments alone and are sometimes described as a "computational microscope." Our work has emphasised lipid membrane contributions to oxygen diffusion and uptake, suggesting that lipid-based pathways along membranes and lipid deposits are likely to accelerate diffusive transport through cells and tissues. Moreover, the lipid and fluid fractions of the tissue are expected to be primary determinants of the local oxygen partial pressure (pO2) as well as the oxygen permeability. Measurements using molecular probes can be influenced by the local molecular environment, due to differential solubility of both the probe and the oxygen molecules in various components of the cell's complex solvent system. The biomolecular simulation work complements experimental studies, which enable evaluation of the models' accuracy and their applicability to real biological systems. Further work is needed to assess fully the possible influence of nanoscale crowders and obstacles (especially protein molecules) on tissue-level diffusive transport of oxygen. Likewise, water-rich carbohydrate layers, such as the glycocalyx, should be evaluated as potential barriers to oxygen transport. Insights gained through biophysical modelling studies could be broadly relevant to clinical phenomena affected by tissue oxygenation, such as tumour radiotherapy, ischaemia, neuropathy, and wound healing.

Phylogenomic conflict coincides with rapid morphological innovation.

Evolutionary biologists have long been fascinated with the episodes of rapid phenotypic innovation that underlie the emergence of major lineages. Although our understanding of the environmental and ecological contexts of such episodes has steadily increased, it has remained unclear how population processes contribute to emergent macroevolutionary patterns. One insight gleaned from phylogenomics is that gene-tree conflict, frequently caused by population-level processes, is often rampant during the origin of major lineages. With the understanding that phylogenomic conflict is often driven by complex population processes, we hypothesized that there may be a direct correspondence between instances of high conflict and elevated rates of phenotypic innovation if both patterns result from the same processes. We evaluated this hypothesis in six clades spanning vertebrates and plants. We found that the most conflict-rich regions of these six clades also tended to experience the highest rates of phenotypic innovation, suggesting that population processes shaping both phenotypic and genomic evolution may leave signatures at deep timescales. Closer examination of the biological significance of phylogenomic conflict may yield improved connections between micro- and macroevolution and increase our understanding of the processes that shape the origin of major lineages across the Tree of Life.

ADHD and cognitive disengagement syndrome symptoms related to self-injurious thoughts and behaviors in early adolescents.

The current study examined attention-deficit/hyperactivity disorder (ADHD) dimensions and cognitive disengagement syndrome (CDS) symptoms in relation to self-injurious thoughts and behaviors (SITBs) in an early adolescent sample. Participants were 341 adolescents ages 10-12 years (52.2% female; 37.8% people of color) recruited from the community. Caregivers reported on CDS and ADHD symptoms. Adolescents completed a rating scale and were administered an interview assessing SITBs. We estimated associations using logistic regression in a stepped fashion: (1) no adjustment, (2) adjustment for sex, race, family income, and psychotropic medication use, and (3) further adjustment for depressive symptoms. In this early adolescent community sample, 22.9% reported a history of suicidal ideation, 8.2% reported a history of a suicide plan, 6.2% reported a history of non-suicidal self-injury (NSSI), and 16.4% met a clinical cutoff for current suicide risk. Across most analyses using rating scale or interview methods, higher mean CDS scores were related to endorsement of suicidal ideation and planning. ADHD inattentive (IN) and hyperactive-impulsive (HI) symptoms were associated with endorsement of NSSI, and ADHD-IN symptoms were associated with thoughts of suicide and/or plan measured via questionnaire, though effects were less robust and not significant, potentially due to low base rates impacting statistical power. This study adds to a growing body of research highlighting the importance of screening for CDS symptoms among individuals with and without ADHD. More research, especially longitudinal work, is needed that examines possible differential pathways to SITBs by ADHD and CDS symptoms to advance SITB prevention, early detection, and intervention.

The evaluation effect of nanoliposome-loaded Mito-Tempo on sperm parameters during human sperm cryopreservation.

AIM: The aim of this study is the evaluation effect of nanoliposome-loaded Mito-Tempo on sperm parameters during human sperm cryopreservation. METHODS: Semen samples of 50 Asthenoteratozoospermia men (random) were collected. Sperm parameters were analyzed based on World Health Organization (WHO, 2010) criteria (2021) and each sample was divided into 5 groups (E1-E5). E1 (control group): the sperm was cryopreserved without nanoliposome, and Mito-Tempo. E2: sperm cryopreservation with Mito-Tempo-loaded nanoliposome (Mito-Tempo 0.1 mM) + freezing medium. E3: sperm cryopreservation with Mito-Tempo-loaded nanoliposome (Mito-Tempo 0.2 mM) + freezing medium. E4: in this group, the cryopreservation sperm with Mito-Tempo 0.3 mM + freezing medium. E5: the cryopreservation sperm with Mito-Tempo 0.2 mM + freezing medium. RESULTS: The result of this study indicated that sperm parameters and total antioxidant capacity (TAC) significantly increase in E3 and E4 groups, compared to E1, E2, and E5 groups respectively (P < 0.05). The percentage of abnormal morphology, DNA fragmentation index (DFI), malondialdehyde (MDA), and the levels of ROS significantly decrease in E3 and E4 groups, compared to E1, E2, and E5 groups (P < 0.05). In addition, the sperm parameters and stress oxidative factors significantly improve in E3 group compared to other groups (P < 0.05). CONCLUSIONS: In conclusion, the combination of Mito-Tempo with nanoliposome due to its ability to cooperate with lipid layers may lead to significant performance in reducing oxidative stress damage and increasing the quality of sperm parameters.

Electrochemical Characterization of a Novel Organoelectrocatalyst, 7-Azabicyclo[2.2.1]heptan-7-ol (ABHOL), and Its Application to Electrochemical Sensors.

Electrochemical enzyme sensors are suitable for simple monitoring methods, for example, as glucose sensors for diabetic patients; however, they have several disadvantages arising from the properties of the enzyme. Therefore, non-enzymatic electrochemical sensors using functional molecules are being developed. In this paper, we report the electrochemical characterization of a new hydroxylamine compound, 7-azabicyclo[2.2.1]heptan-7-ol (ABHOL), and its application to glucose sensing. Although the cyclic voltammogram for the first cycle was unstable, it was reproducible after the second cycle, enabling electrochemical analysis of ethanol and glucose. In the first cycle, ABHOL caused complex reactions, including electrochemical oxidation and comproportionation with the generated oxoammonium ions. The electrochemical probe performance of ABHOL was more efficient than the typical nitroxyl radical compound, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), and had similar efficiency to 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO), which is activated by the bicyclic structure. The results demonstrated the advantages of ABHOL, which can be synthesized from inexpensive materials via simple methods.

The Cellular and Organismal Effects of Nitroxides and Nitroxide-Containing Nanoparticles.

Nitroxides are stable free radicals that have antioxidant properties. They react with many types of radicals, including alkyl and peroxyl radicals. They act as mimics of superoxide dismutase and stimulate the catalase activity of hemoproteins. In some situations, they may exhibit pro-oxidant activity, mainly due to the formation of oxoammonium cations as products of their oxidation. In this review, the cellular effects of nitroxides and their effects in animal experiments and clinical trials are discussed, including the beneficial effects in various pathological situations involving oxidative stress, protective effects against UV and ionizing radiation, and prolongation of the life span of cancer-prone mice. Nitroxides were used as active components of various types of nanoparticles. The application of these nanoparticles in cellular and animal experiments is also discussed.

Effect of Selected Antioxidants on the In Vitro Aging of Human Fibroblasts.

The modification of the replicative lifespan (RLS) of fibroblasts is of interest both from a knowledge point of view and for the attenuation of skin aging. The effect of six antioxidants at a concentration of 1 µM on the replicative lifespan of human dermal fibroblasts was studied. The nitroxide 4-hydroxy-TEMPO (TEMPOL), ergothioneine, and Trolox extended the replicative lifespan (RLS) (40 ± 1 population doublings (PD)) by 7 ± 2, 4 ± 1, and 3 ± 1 PD and lowered the expression of p21 at late passages. Coumaric acid, curcumin and resveratrol did not affect the RLS . The level of reactive oxygen species (ROS) was decreased or not affected by the antioxidants although TEMPOL and coumaric acid decreased the level of glutathione. Only ergothioneine and resveratrol decreased the level of protein carbonylation. The antioxidants that could prolong the RLS elevated the mitochondrial membrane potential. Protecting the activity of mitochondria seems to be important for maintaining the replicative capacity of fibroblasts.

Examining cognitive disengagement syndrome in a psychiatric outpatient sample: Psychometric support and associations with internalizing symptoms and sleep problems.

OBJECTIVE: The internal (structural) and external validity of a self-report measure of cognitive disengagement syndrome (CDS, formerly sluggish cognitive tempo) relative to a self-report measure of attention-deficit/hyperactivity disorder-inattention (ADHD-IN) was evaluated with adults from university outpatient psychiatric clinics in Turkey. METHODS: A total of 274 outpatients (75.9% women; ages 18-64 years; Mage = 31.06; SDage = 10.84; 50.4% anxiety disorders; 41.6% depressive disorders; 2.9% ADHD; 1.5% sleep disorders; 0.7% eating disorders; 2.9% no mental disorder) completed self-report measures of CDS, ADHD-IN, ADHD-hyperactivity/impulsivity (HI), sleep problems, depression, and stress. RESULTS: All 15 CDS symptoms measured by the Adult Concentration Inventory (ACI) showed convergent (moderate to high loadings on the CDS factor) and discriminant (loading close to zero on the ADHD-IN factor) validity. CDS also showed stronger first-order and unique associations than ADHD-IN with sleep problems, depression, anxiety, and stress, whereas ADHD-IN showed stronger first-order and unique associations than CDS with ADHD-HI. CONCLUSION: This is the first study to provide support for the scores from this 15 item self-report measure of CDS by the ACI in a clinical sample of adults, with findings consistent with previous studies examining parent and teacher rating scale measures with the same 15 CDS symptoms. These findings provide additional support for usefulness of these 15 CDS symptoms as measured by the ACI to study CDS across various cultures.