Relative Activity Research Articles

Reduced Achilles tendon stiffness in aging associates with higher metabolic cost of walking

The mechanisms responsible for increased metabolic cost of walking in older adults are poorly understood. We recently proposed a theoretical premise by which age-related reductions in Achilles tendon stiffness (kAT) can disrupt the neuromechanics of calf muscle force production and contribute to faster rates of oxygen consumption during walking. The purpose of this study was to objectively evaluate this premise. We quantified kAT at a range of matched relative activations prescribed using electromyographic biofeedback and walking metabolic cost and ankle joint biomechanics in a group of 15 younger (age: 23±4 yrs) and 15 older adults (age: 72±5 yrs). Older adults averaged 44% lower kAT than younger adults at matched triceps surae activations during isokinetic dorsiflexion tasks on a dynamometer (p=0.046). Older adults also walked with a 17% higher net metabolic power (p=0.017) but indistinguishable peak Achilles tendon forces than younger adults. Thus, data implicate altered tendon length-tension relations with age more than differences in the operating region of those length-tension relations between younger and older adults. In addition, we discovered empirical evidence that lesser kAT - likely due to the shorter muscle lengths and thus higher relative activations it imposes - was positively correlated with higher net metabolic power during walking (r=-0.365, p=0.048). These results pave the way for interventions focused on restoring ankle muscle-tendon unit structural stiffness to improve walking energetics in aging.

Oscillatory drive is increased and steadiness is impaired when torque but not EMG is matched during a fatiguing contraction.

The increasing descending drive needed to sustain a submaximal isometric torque makes it difficult to isolate fatigue-related changes to neural excitability because evoked electromyographic (EMG) responses are influenced by the relative activation of the motoneuron pool. Hence, it is becoming increasingly common to investigate fatigue using a sustained contraction with maintained output from the motoneuron pool; i.e., matched surface EMG. Although this approach controls motoneuron pool output, it is unknown how cortical contributions to ongoing muscle activity or common modulation between muscles is altered during a matched-EMG contraction. During separate visits, 16 participants performed a sustained 10-min isometric elbow flexion contraction at 20% maximal voluntary contraction (MVC) torque or the level of integrated biceps brachii EMG recorded at 20% MVC torque. Electroencephalographic and surface EMG recordings were obtained from the sensorimotor area and biceps and triceps brachii, respectively. The matched-torque contraction caused increased corticomuscular coherence for biceps brachii (~75%) and intermuscular coherence (~97%), but reduced MVC torque (~33%), voluntary activation (~9%), and torque steadiness (~83%). In contrast, the matched-EMG contraction caused reduced MVC torque (~21%), with no change in coherence, voluntary activation, or EMG steadiness. Further, participants reported higher ratings of perceived effort scores by 6min into the matched-torque compared to matched-EMG contraction. These findings indicate that, during a matched-torque contraction, the nervous system enhances common oscillatory activity to continue the task, but this does not prevent degradation of performance (torque steadiness). In contrast, when motoneuron pool output was clamped, other neural strategies are used to maintain muscle output.

Exploring the Relationship Between CAIDE Dementia Risk and EEG Signal Activity in a Healthy Population

Background: Accounting for dementia risk factors is essential in identifying people who would benefit most from intervention programs. The CAIDE dementia risk score is commonly applied, but its link to brain function remains unclear. This study aims to determine whether the variation in this score is associated with neurophysiological changes and cognitive measures in normative individuals. Methods: The sample comprised 38 participants aged between 54 and 79 (M = 67.05; SD = 6.02). Data were collected using paper-and-pencil tests and electroencephalogram (EEG) recordings in the resting state, channels FP1 and FP2. The EEG signals were analyzed using Power Spectral Density (PSD)-based features. Results: The CAIDE score is positively correlated with the relative power activation of the θ band and negatively correlated with the MMSE cognitive test score, and MMSE variations align with those found in distributions of EEG-extracted PSD-based features. Conclusions: The findings suggest that CAIDE scores can identify individuals without noticeable cognitive changes who already exhibit brain activity similar to that seen in people with dementia. They also contribute to the convergent validity between CAIDE and the risk of cognitive decline. This underscores the importance of early monitoring of these factors to reduce the incidence of dementia.

Contrasting Historical and Physical Perspectives in Asymmetric Catalysis: ΔΔG≠ versus Enantiomeric Excess

AbstractWith the rise of machine learning (ML), the modeling of chemical systems has reached a new era and has the potential to revolutionize how we understand and predict chemical reactions. Here, we probe the historic dependence on utilizing enantiomeric excess (ee) as a target variable and discuss the benefits of using relative Gibbs free activation energies (ΔΔG≠), grounded firmly in transition‐state theory, emphasizing practical benefits for chemists. This perspective is intended to discuss best practices that enhance modeling efforts especially for chemists with an experimental background in asymmetric catalysis that wish to explore modelling of their data. We outline the enhanced modeling performance using ΔΔG≠, escaping physical limitations, addressing temperature effects, managing non‐linear error propagation, adjusting for data distributions and how to deal with unphysical predictions,in order to streamline modeling for the practical chemist and provide simple guidelines to strong statistical tools. For this endeavor, we gathered ten datasets from the literature covering very different reaction types. We evaluated the datasets using fingerprint‐, descriptor‐, and graph neural network‐based models. Our results highlight the distinction in performance among varying model complexities with respect to the target representation, emphasizing practical benefits for chemists.

Contrasting Historical and Physical Perspectives in Asymmetric Catalysis: ▵▵G≠ versus Enantiomeric Excess.

With the rise of machine learning (ML), the modeling of chemical systems has reached a new era and has the potential to revolutionize how we understand and predict chemical reactions. Here, we probe the historic dependence on utilizing enantiomeric excess (ee) as a target variable and discuss the benefits of using relative Gibbs free activation energies (ΔΔG≠), grounded firmly in transition-state theory, emphasizing practical benefits for chemists. This perspective is intended to discuss best practices that enhance modeling efforts especially for chemists with an experimental background in asymmetric catalysis that wish to explore modelling of their data. We outline the enhanced modeling performance using ΔΔG≠, escaping physical limitations, addressing temperature effects, managing non-linear error propagation, adjusting for data distributions and how to deal with unphysical predictions,in order to streamline modeling for the practical chemist and provide simple guidelines to strong statistical tools. For this endeavor, we gathered ten datasets from the literature covering very different reaction types. We evaluated the datasets using fingerprint-, descriptor-, and graph neural network-based models. Our results highlight the distinction in performance among varying model complexities with respect to the target representation, emphasizing practical benefits for chemists.

Encoding of vibrotactile stimuli by mechanoreceptors in rodent glabrous skin.

Somatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in rodent glabrous skin has received scant attention, unlike in primates where glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal patterning of LTMR spikes. Rate coding depends on the probability of a spike occurring on each stimulus cycle (reliability) whereas temporal coding depends on the timing of spikes relative to the stimulus cycle (precision). Using in vivo extracellular recordings in male rats and mice of either sex, we measured the reliability and precision of LTMR responses to tactile stimuli including sustained pressure and vibration. Similar to other species, rodent LTMRs were separated into rapid-adapting (RA) or slow-adapting (SA) based on their response to sustained pressure. However, unlike the dichotomous frequency preference characteristic of RA1 and RA2/Pacinian afferents in other species, rodent RAs fell along a continuum. Fitting generalized linear models (GLMs) to experimental data reproduced the reliability and precision of rodent RAs. The resulting model parameters highlight key mechanistic differences across the RA spectrum; specifically, the integration window of different RAs transitions from wide to narrow as tuning preferences across the population move from low to high frequencies. Our results show that rodent RAs can support both rate and temporal coding, but their heterogeneity suggests that co-activation patterns play a greater role in population coding than for dichotomously tuned primate RAs.Significance Statement Our sense of touch starts with activation of nerve fibres in the skin. Although response properties of various fibre types are well-established in other species (e.g. primates), quantitative characterization in rats and mice is limited. To fill this gap, we performed a comprehensive electrophysiological investigation into the coding properties of tactile fibres in rodent non-hairy skin and then simulated these fibres to explain differences in their responses. We show that rodent tactile fibres resemble those from other species, but that their heterogeneity at the population level may differ, with potentially important implications for encoding of touch. Simulations reveal intrinsic mechanisms that support this heterogeneity and provide a useful tool to explore somatosensation in rodents.

Maintained volitional activation of the muscle alters the cortical processing of proprioceptive afference from the ankle joint

Cortical proprioceptive processing of intermittent, passive movements can be assessed by extracting evoked and induced electroencephalographic (EEG) responses to somatosensory stimuli. Although the existent prior research on somatosensory stimulations, it remains unknown to what extent ongoing volitional muscle activation modulates the proprioceptive cortical processing of passive ankle-joint rotations.Twenty-five healthy volunteers (28.8 ± 7 yr, 14 males) underwent a total of 100 right ankle-joint passive rotations (4° dorsiflexions, 4 ± 0.25 s inter-stimulus interval, 30°/s peak angular velocity) evoked by a movement actuator during passive condition with relaxed ankle and active condition with a constant plantarflexion torque of 5 ± 2.5 Nm. Simultaneously, EEG, electromyographic (EMG) and kinematic signals were collected. Spatiotemporal features of evoked and induced EEG responses to the stimuli were extracted to estimate the modulation of the cortical proprioceptive processing between the active and passive conditions.Proprioceptive stimuli during the active condition elicited robustly ∼26 % larger evoked response and ∼38 % larger beta suppression amplitudes, but ∼42 % weaker beta rebound amplitude over the primary sensorimotor cortex than the passive condition, with no differences in terms of response latencies.These findings indicate that the active volitional motor task during naturalistic proprioceptive stimulation of the ankle joint enhances related cortical activation and reduces related cortical inhibition with respect to the passive condition. Possible factors explaining these results include mechanisms occurring at several levels of the proprioceptive processing from the peripheral muscle (i.e. mechanical, muscle spindle status, etc.) to the different central (i.e. spinal, sub-cortical and cortical) levels.

Evaluating the Role of Nrf-2/HO-1 Pathway in Glioblastoma Treatment Efficacy: A Co-Culture Study

Objective: Glioblastoma (GB) is a highly lethal form of brain tumor. Although standard therapy appears to be effective, the survival time is quite short, and the recurrence rate is high. Bortezomib (BTZ), is a proteasome inhibitor, used in GB therapies and resulted in serious off-target effects. Carfilzomib (CFZ), is an alternative for BTZ, has known with nonserious off-target effects. This study aimed to examine the potential off-target effects caused by BTZ and CFZ in terms of the therapy related activation of antioxidant mechanisms regarding to Nuclear factor (erythroid-derived 2)-like 2 (Nrf-2)/Heme Oxygenase-1 (HO-1)-dependent response. Methods: GB cells were co-cultured with heathy astrocyte (HA) cells to mimic the tumor microenvironment in some extent. Cell viability was determined following ionizing radiation (IR), temozolomide (TMZ), BTZ and CFZ alone and in combination. Nrf-2 and HO-1 protein expressions were analyzed by western blotting assay. Results: Co-culture results showed that the GB cells in the BTZ-treated groups expressed higher levels of Nrf-2 and HO-1 than in the CFZtreated groups. In the HAs, the group treated with CFZ showed higher Nrf-2 expression than the group treated with BTZ alone, while the same groups in combination with TMZ&IR showed exactly opposite results. HO-1 expression was also not seen in any of the HA groups. Conclusion: The significant increase in Nrf-2 levels in the CFZ-treated group in the HAs could also be interpreted as CFZ promoting the defence of healthy cells against therapy-induced stress conditions. Although further studies are needed, these preliminary results show that the evaluation of CFZ as a second-line therapy could be a milestone for the treatment of GB.

Exploring the role of traditional Chinese medicine rehabilitation in stroke based on microRNA-mediated pyroptosis: A review.

Stroke, also known as "cerebrovascular accident," is a disease caused by acute impairment of brain circulation, which has a high rate of disability and mortality. Ischemic stroke (IS) is the most common type of stroke and a major cause of death and disability worldwide. At present, there are still many limitations in the treatment of IS, so it may be urgent to explore more treatments for IS. In recent years, the clinical application of traditional Chinese medicine rehabilitation methods such as traditional Chinese medicine, acupuncture, massage, traditional exercises and modern rehabilitation technology has achieved good results in the treatment of IS. Concurrently, studies have identified microRNA (miRNA), which are intimately associated with traditional Chinese medicine rehabilitation, as regulators of pyroptosis through their influence on microglia activity, inflammatory response, oxidative stress, angiogenesis and other factors, but at present, the mechanism of this direction has not been systematically summarized. Consequently, this article delineates in detail the specific role of miRNA in IS and the related activation pathways of pyroptosis in IS. This article presents a detailed discussion of the role of microRNA-mediated pyroptosis in IS, with a particular focus on the signaling pathways involved. The aim is to provide new insights for the research of traditional Chinese medicine (TCM) rehabilitation in the prevention and treatment of IS. In addition, the article explores the potential of TCM rehabilitation in regulating miRNA-mediated pyroptosis to intervene in IS.

Transformation of sartan blood pressure regulators by ferrate(VI) and its activation systems: Kinetics and mechanisms

With the increasing number of patients diagnosed with hypertension, the annual consumption of sartan drugs has surged, resulting in their ubiquitous detection in aquatic environments. This increases concerns about their environmental persistence and unexpected toxicity. This study explores the applications of ferrate(VI) (Fe(VI)) in removing sartan blood pressure regulators (losartan (LOS), valsartan (VAL), and telmisartan (TEL)). Results demonstrate that sartans could be effectively removed by Fe(VI). Oxidation of LOS by Fe(VI) was pH-dependent at pH 7.0–9.0, with HFeO4– dominating the reaction. The second-order rate constants (kapp) of LOS with Fe(VI) decreased with increasing solution pH, and kapp was calculated to be 148.37 M−1 s−1 at pH 8.0. Furthermore, the Fe(VI)-Fe(III), Fe(VI)-S(IV), and Fe(VI)-S2O32– systems demonstrated the enhancement for the elimination of LOS, while the Fe(VI)–HCO3– system inhibited the reaction. Oxidizing product (OP) analysis suggested that the major transformation patterns of LOS, VAL, and TEL treated by Fe(VI) and its activation systems included oxidation, imidazole ring cleavage, cyclization, N-dealkylation, and bond cleavage. Multiple OPs were estimated to be more persistent and mobile than parent sartans, while their toxicity toward aquatic organisms might be several times lower than those of their parents. Overall, this study elucidates the oxidizing feasibility of Fe(VI) and related activation systems to eliminate sartans in water treatment.

Influence of varying branched-chain amino acid ratio in diets containing corn gluten meal, L-isoleucine, and L-valine on 0–21 d turkey poult performance, relative mTOR activation, and apparent ileal amino acid digestibility

Influence of varying branched-chain amino acid ratio in diets containing corn gluten meal, L-isoleucine, and L-valine on 0–21 d turkey poult performance, relative mTOR activation, and apparent ileal amino acid digestibility

Unveiling Microbial Diversity: Raman Spectroscopy's Discrimination of Clostridium and Related Genera.

In the clinical environment, the identification of phylogenetic closely related genera and species like Clostridium and Bacillus spp. is challenging. Both genera contain representatives of pathogenic and nonpathogenic species that need to be distinguished for a proper diagnostic read-out. Therefore, reliable and accurate detection methods must be employed for the correct identification of these genera and species. Despite their high pathogenicity, clostridial infections and food contaminations present significant challenges due to their unique cultivation conditions and developmental needs. Therefore, in many diagnostic protocols, the toxins are used for microbiological documentation. However, the applied laboratory methods suffer in accuracy, sometimes require large bacterial loads to provide reliable results, and cannot differentiate pathogenic from nonpathogenic strains. Here, Raman spectroscopy was employed to create an extensive Raman database consisting of pathogenic and nonpathogenic Bacillus and Clostridium species. These genera, as well as representatives of Paraclostridium and Clostridioides were specifically selected for their phylogenetic relation, cultivation conditions, and metabolic activity. A chemometric evaluation of the Raman spectra of single vegetative cells revealed a high discriminating power at the genus level. However, bacilli are considerably easier to classify at the species level than clostridia. The discrimination between the genera and species was based on their phylogeny and not their aerobic and anaerobic cultivation conditions. These encouraging results demonstrated that Raman spectroscopy coupled with chemometrics is a robust and helpful method for differentiating Clostridium species from Bacillus, Clostridioides, and Paraclostridium species. This approach has the potential to be a valuable tool in clinical diagnostics.

Essays on the female and male mentality in Russian institutions of matrimony and parenthood (until the middle of the XIX century)

The article identifies, systematizes and analyzes patterns of legal and generally social inequality of a woman (regarding the status of a man - father and husband) in the period preceding the creation of obvious prerequisites for her emancipation, including before the October Revolution of 1917. At the same time, elements of female activity in family relations and civil relations are demonstrated, which, in our opinion, distinguishes the Russian situation for the better from Western variations of the same period. The authors form an idea of the contradictory interaction of female and male mentalities in family law and related institutions: the power of husband and father, being close to absolute, supported by law, church and custom, even in the era under study assumed restrictions and did not exclude some freedom of will of a woman. This, along with the political and economic factors of later times, formed the prerequisite for the dynamic evolution of female emancipation.

Characterization of the PGNAA neutron beam of Isfahan MNSR through the calculations and different measurement methods

In this work, the significant characterization of the neutron beam used in the PGNAA facility of the Isfahan MNSR research reactor has been determined using both calculation and measurement. The important parameters of the beam include flux and energy distribution of neutrons, cadmium ratio, thermal neutron content (TNC), and neutron-to-gamma ratio (n/γ). In this regard, Monte Carlo simulation and experiments were implemented to find these characteristics. The experiments have been carried out through the relative and absolute activation methods using irradiation of indium foil and mica in combination with uranium foil. Moreover, the condition of the neutron beam has been investigated in terms of contamination with fast neutrons using the germanium triangle method. The results showed that the MNSR has acceptable characteristics for performing PGNAA analyses despite its low power.

Prefrontal cortex-nucleus reuniens-hippocampus network exhibits sex-differentiated responses to stress and antidepressant treatment in rats.

Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression. In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine. Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity. RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females. Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.

Rescue of Familial Lecithin:Cholesterol Acyltranferase Deficiency Mutations with an Allosteric Activator.

Lecithin:cholesterol acyltransferase (LCAT) deficiencies represent severe disorders characterized by aberrant cholesterol esterification in plasma, leading to life-threatening conditions. This study investigates the efficacy of Compound 2, a piperidinyl pyrazolopyridine allosteric activator that binds the membrane-binding domain of LCAT, in rescuing the activity of LCAT variants associated with disease. The variants K218N, N228K, and G230R, all located in the cap and lid domains of LCAT, demonstrated notable activity restoration in response to Compound 2. Molecular dynamics simulations and structural modeling indicate that these mutations disrupt the lid and membrane binding domain, with Compound 2 potentially dampening these structural alterations. Conversely, variants such as M252K and F382V in the cap and α/β-hydrolase domain, respectively, exhibited limited or no rescue by Compound 2. Future research should prioritize in vivo investigations that would validate the therapeutic potential of Compound 2 and related activators in familial LCAT deficiency patients with mutations in the cap and lid of the enzyme. SIGNIFICANCE STATEMENT: Lecithin:cholesterol acyltranferase (LCAT) catalyzes the first step of reverse cholesterol transport, namely the esterification of cholesterol in high density lipoprotein particles. Somatic mutations in LCAT lead to excess cholesterol in blood plasma and, in severe cases, kidney failure. In this study, we show that recently discovered small molecule activators can rescue function in LCAT-deficient variants when the mutations occur in the lid and cap domains of the enzyme.

Precision fMRI and cluster-failure in the individual brain.

Advances in neuroimaging acquisition protocols and denoising techniques, along with increasing magnetic field strengths, have dramatically improved the temporal signal-to-noise ratio (tSNR) in functional magnetic resonance imaging (fMRI). This permits spatial resolution with submillimeter voxel sizes and ultrahigh temporal resolution and opens a route toward performing precision fMRI in the brains of individuals. Yet ultrahigh spatial and temporal resolution comes at a cost: it reduces tSNR and, therefore, the sensitivity to the blood oxygen level-dependent (BOLD) effect and other functional contrasts across the brain. Here we investigate the potential of various smoothing filters to improve BOLD sensitivity while preserving the spatial accuracy of activated clusters in single-subject analysis. We introduce adaptive-weight smoothing with optimized metrics (AWSOM), which addresses this challenge extremely well. AWSOM employs a local inference approach that is as sensitive as cluster-corrected inference of data smoothed with large Gaussian kernels, but it preserves spatial details across multiple tSNR levels. This is essential for examining whole-brain fMRI data because tSNR varies across the entire brain, depending on the distance of a brain region from the receiver coil, the type of setup, acquisition protocol, preprocessing, and resolution. We found that cluster correction in single subjects results in inflated family-wise error and false positive rates. AWSOM effectively suppresses false positives while remaining sensitive even to small clusters of activated voxels. Furthermore, it preserves signal integrity, that is, the relative activation strength of significant voxels, making it a valuable asset for a wide range of fMRI applications. Here we demonstrate these features and make AWSOM freely available to the research community for download.

Activism as technology of the posthuman self: towards a more relevant school

ABSTRACT This paper aims to make a theoretical contribution to the field of student activism in relation to the school. In an age marked by ecological, economic and technological change, and where certainties based on Humanism and anthropocentricism continue to be eroded, this paper explores possibilities for reintegrating the school as meaningful to the ethico-political development of students. Activism is positioned in this paper as a means by which students can actualise their ethico-political agency in relation to the self, others and the world. This paper therefore urges school leaders to recognise the potential of knowledge generated through affirmative youth activism and to find a space for this knowledge within the school. This is particularly important within a context of growing youth disillusionment with formal schooling and its inadequate response to the crises of our age. This paper theoretically develops a relational space within the school for the “offical” knowledge of this education to be brought into meaningful political conversation with the “minor” knowledge generated through youth activism. These theorisations will be supported by case studies taken from the empirical literature on youth activism.

Abstract Tu133: Cardiac Adaptations and Mitochondrial Protection Through Long Noncoding RNAs Regulation in Mice on a Ketogenic Diet

Background: Heart failure, characterized by a metabolic imbalance, leads to impaired mitochondrial ATP production. Ketone bodies not only serve as an alternate energy source but also mitigate heart failure by reducing cardiac remodeling and inflammation. The role of long noncoding RNAs (lncRNAs) in cardiac remodeling and mitochondrial metabolism is increasingly appreciated, and this study examines the effect of ketogenic diet on cardiac lncRNA regulation and mitochondrial protection. Methods and Results: In a six-month study, 10-week-old male and female C57BL/6J mice were assigned to either a control diet (10% fat, 20% protein, 70% carbohydrate) or a ketogenic diet (Keto; 80% fat, 15% protein, 5% carbohydrate). Data were analyzed using unpaired two-tailed t-tests (GraphPad Prism) and reported as mean ± SE. The keto diet significantly increased blood ketone bodies (n=36/group), indicating ketosis, and led to weight gain as well as a significant decrease in heart mass relative to body weight, suggesting cardiac metabolic adaptation (Fig 1A-B) . The cardiac expression analysis of lncRNAs Anril, Caren, Carmn, Gm15441, Malat1, Miat, and Oip5-as1 via qPCR (n=13/group) revealed significant upregulation of Anril and Malat1 in the Keto hearts ( Fig 1C-D ), indicating their potential regulatory roles under ketogenic conditions. Sex-specific differences were not observed in the lncRNA expressions. Key proteins involved in mitochondrial biogenesis, protection, and metabolic adaptation, including Nrf2 and PGC1α, were significantly increased at both mRNA and protein levels (n=6-10) in the hearts of mice on keto diet ( Fig 1E-H ). Conclusion: A six-month ketogenic diet in mice promotes cardiometabolic adaptations characterized by a reduction in relative heart mass and activation of key proteins involved in mitochondrial biogenesis and protection possibly through lncRNAs Anril and Malat1. These findings shed light on novel molecular targets and the potential of ketogenic diet/ketone bodies in treating heart failure.

Endogenous estrogens and brain activation during verbal memory encoding and recognition in the postmenopause.

Determine associations of endogenous estrogens with memory systems in the postmenopausal brain and evaluate clinical significance. In the MsBrain cohort (n=199, mean age 59.3+3.9 years, 83.9% white), we examined the cross-sectional association of serum estradiol and estrone, measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), during a functional magnetic resonance imaging (fMRI) task of word encoding and recognition. To characterize the clinical significance of those associations, we examined the magnitude of activation in relation to a neuropsychological measures of memory and affect. Endogenous estradiol was positively associated with activation in temporal and frontal cortices during encoding and negatively associated with one prefrontal region during recognition (p<.05). Activation in the left inferior frontal gyrus was associated with memory performance (β(SE)= 0.004(0.002), p<.05), and anxiety (β(SE)= -0.100(0.050), p<.05). The left middle frontal gyrus was associated with memory performance (β(SE)= 0.006(0.002), p<.01), depression, and anxiety. The left superior temporal gyrus (STG) was associated with depression (β(SE)= -0.083(0.036), p<.05) and anxiety (β(SE)= -0.134(0.058), p<.05). Estrone was positively associated with activation in a range of brain areas including bilateral STG and right superior frontal gyrus during encoding (p<.05). Activation of the left insula an precental gyrus were associated with symptoms of depression and anxiety. None related to memory. The function of brain areas critical to memory performance varies with estrogen levels in the postmenopause, even though those levels are low. Higher levels of estradiol may facilitate memory performance through enhanced function of temporal and frontal cortices during encoding of verbal material.