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Chronic exposure to elevated levels of manganese (Mn) may cause a neurological disorder referred to as manganism. The transcription factor REST is dysregulated in several neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. REST upregulated tyrosine hydroxylase and induced protection against Mn toxicity in neuronal cultures. In the present study, we investigated if dopaminergic REST plays a critical role in protecting against Mn-induced toxicity in vivo using dopaminergic REST conditional knockout (REST-cKO) mice and REST loxP mice as wild-type (WT) controls. Restoration of REST in the substantia nigra (SN) with neuronal REST AAV vector infusion was performed to further support the role of REST in Mn toxicity. Mice were exposed to Mn (330 µg, intranasal, daily for 3 weeks), followed by behavioral tests and molecular biology experiments. Results showed that Mn decreased REST mRNA/protein levels in the SN-containing midbrain, as well as locomotor activity and motor coordination in WT mice, which were further decreased in REST-cKO mice. Mn-induced mitochondrial insults, such as impairment of fission/fusion and mitophagy, apoptosis, and oxidative stress, in the midbrain of WT mice were more pronounced in REST-cKO mice. However, REST restoration in the SN of REST-cKO mice attenuated Mn-induced neurotoxicity. REST's molecular target for its protection is unclear, but REST attenuated Mn-induced mitochondrial dysregulation, indicating that it is a primary intracellular target for both Mn and REST. These novel findings suggest that dopaminergic REST in the nigrostriatal pathway is critical in protecting against Mn toxicity, underscoring REST as a potential therapeutic target for treating manganism.

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In this article, we argue that social systems with fission-fusion (FF) dynamics are best characterized within a complex adaptive systems (CAS) framework. We discuss how different endogenous and exogenous factors drive scale-dependent network properties across temporal, spatial and social domains. Importantly, this view treats the dynamics themselves as objects of study, rather than variously defined notions of static 'social groups' that have hitherto dominated thinking in behavioural ecology. CAS approaches allow us to interrogate FF dynamics in taxa that do not conform to more traditional conceptualizations of sociality and encourage us to pose new types of questions regarding the sources of stability and change in social systems, distinguishing regular variations from those that would lead to system-level reorganization. This article is part of the theme issue 'Connected interactions: enriching food web research by spatial and social interactions'.

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Because of the diverging needs of individuals, group life can lead to disputes and competition, but it also has many advantages, such as reduced predation risk, information sharing and increased hunting success. Social animals have to maintain group cohesion and need to synchronize activities, such as foraging, resting, social interactions and movements, in order to thrive in groups. Acoustic signals are highly relevant for social dynamics, some because they are long-ranging and others because they are short-ranging, which may serve important within-group functions. However, although there has been an increase in studies concentrating on acoustic communication within groups in the past decade, many aspects of how vocalizations relate to group dynamics are still poorly understood. The aim of this review is to present an overview of our current knowledge on the role of vocalizations in regulating social group dynamics, identify knowledge gaps and recommend potential future research directions. We review the role that vocalizations play in (i) collective movement, (ii) separation risk and cohesion maintenance, (iii) fission-fusion dynamics, and (iv) social networks. We recommend that future studies aim to increase the diversity of studied species and strengthen the integration of state-of-the-art tools to study social dynamics and acoustic signals. This article is part of the theme issue 'The power of sound: unravelling how acoustic communication shapes group dynamics'.

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Although chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) share a multi-male/multi-female societal organization and form male-philopatric groups, disparities in terms of male aggression and stability of temporary parties are thought to exist among them. However, existing research in bonobos has mainly focused on the high social status, prolonged receptivity, and characteristic sexual behaviors of females, leaving the behaviors of males understudied. Moreover, prior comparative studies on Pan suffer from methodological inconsistencies. This study addresses these gaps by employing a uniform observation method to explore party attendance and aggressive interactions among male bonobos in Wamba and male chimpanzees in Kalinzu. Unlike male chimpanzees, which exhibit dispersion in the absence of receptive females in the group, male bonobos showed a lesser degree of such dispersion. Although the overall frequency of aggressive interactions per observation unit did not significantly differ between the two species, the nature of these interactions varied. Notably, severe aggressive behaviors such as physical confrontations among adult males were absent in bonobos, with most aggression occurring between the sons of the two highest-ranking females. Additionally, in bonobos, females actively engaged in polyadic aggressive behavior as aggressors, while all instances of coalitionary aggression in chimpanzees originated from male aggressors. These findings underscore the substantial impact of female behaviors on the observed distinctions in male aggressive interactions between the two species.

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Social structure can emerge from hierarchically embedded scales of movement, where movement at one scale is constrained within a larger scale (e.g. among branches, trees, forests). In most studies of animal social networks, some scales of movement are not observed, and the relative importance of the observed scales of movement is unclear. Here, we asked: how does individual variation in movement, at multiple nested spatial scales, influence each individual's social connectedness? Using existing data from common vampire bats (Desmodus rotundus), we created an agent-based model of how three nested scales of movement-among roosts, clusters and grooming partners-each influence a bat's grooming network centrality. In each of 10 simulations, virtual bats lacking social and spatial preferences moved at each scale at empirically derived rates that were either fixed or individually variable and either independent or correlated across scales. We found that numbers of partners groomed per bat were driven more by within-roost movements than by roost switching, highlighting that co-roosting networks do not fully capture bat social structure. Simulations revealed how individual variation in movement at nested spatial scales can cause false discovery and misidentification of preferred social relationships. Our model provides several insights into how nonsocial factors shape social networks.

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Accumulating evidence highlights the pivotal role of mitochondria in cardiovascular diseases (CVDs). Understanding the molecular mechanisms underlying mitochondrial dysfunction is crucial for developing targeted therapeutics. Recent years have seen substantial advancements in unraveling mitochondrial regulatory pathways in both normal and pathological states and the development of potent drugs. However, specific delivery of drugs into the mitochondria is still a challenge. We present recent findings on regulators of mitochondrial dynamics and reactive oxygen species (ROS), critical factors influencing mitochondrial function in CVDs. We also discuss advancements in drug delivery strategies aimed at overcoming the technical barrier in targeting mitochondria for CVD treatment.

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Social carnivores frequently live in fission-fusion societies, where individuals that share a common territory or home range may be found alone, in subgroups, or altogether. Absolute group size and subgroup size is expected to vary according to resource distribution, but for species that are susceptible to anthropogenic pressures, other factors may be important drivers. African lions (Panthera leo) are the only truly social felid and lion prides are characterized by fission-fusion dynamics with social groups frequently splitting and reforming, and subgroup membership can change continuously and frequently. The number of individuals in a group can be reflective of social, ecological, and anthropogenic conditions. This dynamic behavior makes understanding lion grouping patterns crucial for tailoring conservation measures. The evolution of group living in lions has been the topic of numerous studies, and we drew on these to formulate hypotheses relating to group size and subgroup size variation. Based on data collected from 199 lion groups across eight sites in Kenya, we found that group sizes were smaller when lions were closer to human settlements, suggesting that edge effects are impacting lions at a national scale. Smaller groups were also more likely when they were far from water, and were associated with very low and very high levels of non-tree vegetation. We found significant differences between the study sites, with the Maasai Mara having the largest groups (mean ± SD = 7.7 ± 4.7, range = 1-19), and Amboseli conservation area the smallest (4.3 ± 3.5, range = 1-14). While long-term studies within a single site are well suited to thoroughly differentiate between absolute group size and subgroup size, our study provides unique insight into the correlates of grouping patterns in a vulnerable species at a national scale.

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We previously reported evidence that oxidative stress during aging leads to adverse protein profile changes of brain cortical microvessels (MVs: end arterioles, capillaries, and venules) that affect mRNA/protein stability, basement membrane integrity, and ATP synthesis capacity in mice. As an extension of our previous study, we also found that proteins which comprise the blood-brain barrier (BBB) and regulate mitochondrial quality control were also significantly decreased in the mice's cortical MVs with aging. Interestingly, the neuroinflammatory protein fibrinogen (Fgn) was increased in mice brain MVs, which corresponds with clinical reports indicating that the plasma Fgn concentration increased progressively with aging. In this study, protein-protein interaction network analysis indicated that high expression of Fgn is linked with downregulated expression of both BBB- and mitochondrial fission/fusion-related proteins in mice cortical MVs with aging. To investigate the mechanism of Fgn action, we observed that 2 mg/mL or higher concentration of human plasma Fgn changed cell morphology, induced cytotoxicity, and increased BBB permeability in primary human brain microvascular endothelial cells (HBMECs). The BBB tight junction proteins were significantly decreased with increasing concentration of human plasma Fgn in primary HBMECs. Similarly, the expression of phosphorylated dynamin-related protein 1 (pDRP1) and other mitochondrial fission/fusion-related proteins were also significantly reduced in Fgn-treated HBMECs. Interestingly, DRP1 knockdown by shRNA(h) resulted in the reduction of both BBB- and mitochondrial fission/fusion-related proteins in HBMECs. Our results suggest that elevated Fgn downregulates DRP1, leading to mitochondrial-dependent endothelial and BBB dysfunction in the brain microvasculature.

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ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg-1） and Captopril group （0.002 57 g·kg-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

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Apolipoproteins L1 and L3 (APOLs) are associated at the Golgi with the membrane fission factors phosphatidylinositol 4-kinase-IIIB (PI4KB) and non-muscular myosin 2A. Either APOL1 C-terminal truncation (APOL1Δ) or APOL3 deletion (APOL3-KO [knockout]) reduces PI4KB activity and triggers actomyosin reorganization. We report that APOL3, but not APOL1, controls PI4KB activity through interaction with PI4KB and neuronal calcium sensor-1 or calneuron-1. Both APOLs are present in Golgi-derived autophagy-related protein 9A vesicles, which are involved in PI4KB trafficking. Like APOL3-KO, APOL1Δ induces PI4KB dissociation from APOL3, linked to reduction of mitophagy flux and production of mitochondrial reactive oxygen species. APOL1 and APOL3, respectively, can interact with the mitophagy receptor prohibitin-2 and the mitophagosome membrane fusion factor vesicle-associated membrane protein-8 (VAMP8). While APOL1 conditions PI4KB and APOL3 involvement in mitochondrion fission and mitophagy, APOL3-VAMP8 interaction promotes fusion between mitophagosomal and endolysosomal membranes. We propose that APOL3 controls mitochondrial membrane dynamics through interactions with the fission factor PI4KB and the fusion factor VAMP8.

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According to the ecological model of female social relationships (EMFSR), within-group competition and between-group competition in female-bonded species are shaped by food distribution. Strong between-group contests are expected over large, monopolizable resources and high population density, but not when low-quality food is distributed across large, undefended home ranges. Within-group contests are expected to be more frequent with increasing heterogeneity among feeding sites and with group size. We tested these predictions in female Asian elephants, which show traits associated with infrequent contests-graminivory, high fission-fusion and overlapping home ranges. We examined how food distribution and competitor density affected agonistic interactions within and between female elephant clans (social groupings) in the Kabini grassland, southern India. We found stronger between-clan contest in the grassland than that known from neighbouring forests, and more frequent agonism between females between clans than within clans. Such strong between-clan contest was attributable to the grassland being a food-rich habitat patch, thus supporting the EMFSR. Within-clan agonism was also frequent, but did not increase with food heterogeneity, contradicting the EMFSR. Contrary to recent claims, increasing within-clan agonism with group size suggested ecological constraints on large groups despite high fission-fusion. High population density may explain such frequent contests despite graminivory and fission-fusion.

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Exposure to cigarette smoke and e-cigarettes, with nicotine as the active constituent, contributes to increased health risks associated with asthma. Nicotine exerts its functional activity via nicotinic acetylcholine receptors (nAChRs), and the alpha7 subtype (α7nAChR) has recently been shown to adversely affect airway dynamics. The mechanisms of α7nAChR action in airways, particularly in the context of airway smooth muscle (ASM), a key cell type in asthma, are still under investigation. Mitochondria have garnered increasing interest for their role in regulating airway tone and adaptations to cellular stress. Here mitochondrial dynamics such as fusion versus fission, and mitochondrial Ca2+ ([Ca2+]m), play an important role in mitochondrial homeostasis. There is currently no information on effects and mechanisms by which nicotine regulates mitochondrial structure and function in ASM in the context of asthma. We hypothesized that nicotine disrupts mitochondrial morphology, fission-fusion balance, and [Ca2+]m regulation, with altered mitochondrial respiration and bioenergetics in the context of asthmatic ASM. Using human ASM (hASM) cells from nonasthmatics, asthmatics, and smokers, we examined the effects of nicotine on mitochondrial dynamics and [Ca2+]m. Fluorescence [Ca2+]m imaging of hASM cells with rhod-2 showed robust responses to 10 µM nicotine, particularly in asthmatics and smokers. In both asthmatics and smokers, nicotine increased the expression of fission proteins while decreasing fusion proteins. Seahorse analysis showed blunted oxidative phosphorylation parameters in response to nicotine in these groups. α7nAChR siRNA blunted nicotine effects, rescuing [Ca2+]m, changes in mitochondrial structural proteins, and mitochondrial dysfunction. These data highlight mitochondria as a target of nicotine effects on ASM, where mitochondrial disruption and impaired buffering could permit downstream effects of nicotine in the context of asthma.NEW & NOTEWORTHY Asthma is a major healthcare burden, which is further exacerbated by smoking. Recognizing the smoking risk of asthma, understanding the effects of nicotine on asthmatic airways becomes critical. Surprisingly, the mechanisms of nicotine action, even in normal and especially asthmatic airways, are understudied. Accordingly, the goal of this research is to investigate how nicotine influences asthmatic airways in terms of mitochondrial structure and function, via the a7nAChR.

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Accurate interpretation of the genetic signatures of past demographic events is crucial for reconstructing evolutionary history. Lineage fusion (complete merging, resulting in a single panmictic population) is a special case of secondary contact that is seldom considered. Here, the circumstances under which lineage fusion can be distinguished from population size constancy, growth, bottleneck, and decline were investigated. Multi-locus haplotype data were simulated under models of lineage fusion with different divergence versus sampling lag times (D:L ratios). These pseudo-observed datasets also differed in their allocation of a fixed amount of sequencing resources (number of sampled alleles, haplotype length, number of loci). Distinguishability of lineage fusion versus each of 10 untrue non-fusion scenarios was quantified based on six summary statistics (neutrality tests). Some datasets were also analyzed using extended Bayesian skyline plots. Results showed that signatures of lineage fusion very closely resemble those of decline-high distinguishability was generally limited to the most favorable scenario (D:L = 9), using the most sensitive summary statistics (F S and Z nS), coupled with the optimal sequencing resource allocation (maximizing number of loci). Also, extended Bayesian skyline plots often erroneously inferred population decline. Awareness of the potential for lineage fusion to carry the hallmarks of population decline is critical.

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The social complexity hypothesis for the evolution of communication posits that complex social environments require greater communication complexity for individuals to effectively manage their relationships. We examined how different socially uncertain contexts, reflecting an increased level of social complexity, relate to variation in signalling within and between two species, which display varying levels of fission-fusion dynamics (sympatric-living chimpanzees and sooty mangabeys, Taï National Park, Ivory Coast). Combined signalling may improve message efficacy, notably when involving different perception channels, thus may increase in moments of high social uncertainty. We examined the probability of individuals to emit no signal, single or multisensory or combined (complex) signals, during social approaches which resulted in non-agonistic outcomes. In both species, individuals were more likely to use more combined and multisensory signals in post-conflict approaches with an opponent than in other contexts. The clearest impact of social uncertainty on signalling complexity was observed during chimpanzee fusions, where the likelihood of using complex signals tripled relative to other contexts. Overall, chimpanzees used more multisensory signals than mangabeys. Social uncertainty may shape detected species differences in variation in signalling complexity, thereby supporting the hypothesis that social complexity, particularly associated with high fission-fusion dynamics, promotes signalling complexity.

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Cardiomyocyte hypertrophy, induced by elevated levels of angiotensin II (AngII), plays a crucial role in cardiovascular diseases. Current therapeutic approaches aim to regress cardiac hypertrophy but have limited efficacy. Widely used Japanese Kampo medicines are highly safe and potential therapeutic agents. This study aims to explore the impact and mechanisms by which Moku-boi-to (MBT), a Japanese Kampo medicine, exerts its potential cardioprotective benefits against AngII-induced cardiomyocyte hypertrophy, bridging the knowledge gap and contributing to the development of novel therapeutic strategies. By evaluating the effects of six Japanese Kampo medicines with known cardiovascular efficiency on AngII-induced cardiomyocyte hypertrophy and cell death, we identified MBT as a promising candidate. MBT exhibited preventive effects against AngII-induced cardiomyocyte hypertrophy, cell death and demonstrated improvements in intracellular Ca2+ signaling regulation, ROS production, and mitochondrial function. Unexpectedly, experiments combining MBT with the AT1 receptor antagonist losartan suggested that MBT may target the AT1 receptor. In an isoproterenol-induced heart failure mouse model, MBT treatment demonstrated significant effects on cardiac function and hypertrophy. These findings highlight the cardioprotective potential of MBT through AT1 receptor-mediated mechanisms, offering valuable insights into its efficacy in alleviating AngII-induced dysfunction in cardiomyocytes. The study suggests that MBT holds promise as a safe and effective prophylactic agent for cardiac hypertrophy, providing a deeper understanding of its mechanisms for cardioprotection against AngII-induced dysfunction.

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Vigilance is a widespread behavior that allows individuals to socially acquire information and/or effectively detect potential risks posed by predators and conspecifics. In this study, we aimed to investigate how social factors (i.e., subgroup size, number of males and immatures in the subgroup, presence of fission and fusion events, subgroup activity), individual characteristics (i.e., sex, presence of dependent offspring) and possible vulnerability to predation (i.e., being in smaller subgroups or lower in the canopy) explain variation in vigilance behavior in a wild group of spider monkeys (Ateles geoffroyi). We collected vigilance data during focal samples of all adults, subadults and juveniles of the group (N = 38), and ran generalized linear mixed models with a Bayesian approach. We found that the proportion of time both sexes spent in vigilance increased with subgroup size and during fusion events. Individuals also spent more time in vigilance when the subgroup was resting or socializing compared to other activities. Moreover, the proportion of time spent in vigilance increased in subgroups with more immatures. An alternative model with similar fit suggested that the proportion of time spent in vigilance increased in females when subgroups included more adult and subadult males. Overall, these results suggest that our study group mainly directed vigilance toward conspecifics (i.e., social vigilance), probably as a result of the relatively low predation pressure experienced, and contribute to the understanding of the multiple social factors affecting vigilance in group-living primates.

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CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.

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Obesity-induced skeletal muscle (SKM) inflexibility is closely linked to mitochondrial dysfunction. The present study aimed to evaluate the effects of melatonin on the red vastus lateralis (RVL) muscle in obese rat models at the molecular and morphological levels. Five-week-old male Zücker diabetic fatty (ZDF) rats and their age-matched lean littermates (ZL) were orally treated either with melatonin (10 mg/kg body weight (BW)/24 h) (M-ZDF and M-ZL) or non-treated (control) (C-ZDF and C-ZL) for 12 weeks. Western blot analysis showed that mitochondrial fission, fusion, and autophagy were altered in the C-ZDF group, accompanied by reduced SIRT1 levels. Furthermore, C-ZDF rats exhibited depleted ATP production and nitro-oxidative stress, as indicated by increased nitrites levels and reduced SOD activity. Western blotting of MyH isoforms demonstrated a significant decrease in both slow and fast oxidative fiber-specific markers expression in the C-ZDF group, concomitant with an increase in the fast glycolytic fiber markers. At the tissue level, marked fiber atrophy, less oxidative fibers, and excessive lipid deposition were noted in the C-ZDF group. Interestingly, melatonin treatment partially restored mitochondrial fission/fusion imbalance in the RVL muscle by enhancing the expression of fission (Fis1 and DRP1) markers and decreasing that of fusion (OPA1 and Mfn2) markers. It was also found to restore autophagy, as indicated by increased p62 protein level and LC3BII/I ratio. In addition, melatonin treatment increased SIRT1 protein level, mitochondrial ATP production, and SOD activity and decreased nitrites production. These effects were associated with enhanced oxidative phenotype, as evidenced by amplified oxidative fiber-specific markers expression, histochemical reaction for NADH enzyme, and muscular lipid content. In this study, we showed that melatonin might have potential therapeutic implications for obesity-induced SKM metabolic inflexibility among patients with obesity and T2DM.

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Fission-fusion events, i.e. changes to the size and composition of animal social groups, are a mechanism to adjust the social environment in response to short-term changes in the cost-benefit ratio of group living. Furthermore, the time and location of fission-fusion events provide insight into the underlying drivers of these dynamics. Here, we describe a method for identifying group membership over time and for extracting fission-fusion events from animal tracking data. We applied this method to high-resolution GPS data of free-ranging sheep (Ovis aries). Group size was highest during times when sheep typically rest (midday and at night), and when anti-predator benefits of grouping are high while costs of competition are low. Consistent with this, fission and fusion frequencies were highest during early morning and late evening, suggesting that social restructuring occurs during periods of high activity. However, fission and fusion events were not more frequent near food patches and water resources when adjusted for overall space use. This suggests a limited role of resource competition. Our results elucidate the dynamics of grouping in response to social and ecological drivers, and we provide a tool for investigating these dynamics in other species.

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Diabetic cardiomyopathy describes decreased myocardial function in diabetic patients in the absence of other heart diseases such as myocardial ischemia and hypertension. Recent studies have defined numerous molecular interactions and signaling events that may account for deleterious changes in mitochondrial dynamics and functions influenced by hyperglycemic stress. A metabolic switch from glucose to fatty acid oxidation to fuel ATP synthesis, mitochondrial oxidative injury resulting from increased mitochondrial ROS production and decreased antioxidant capacity, enhanced mitochondrial fission and defective mitochondrial fusion, impaired mitophagy, and blunted mitochondrial biogenesis are major signatures of mitochondrial pathologies during diabetic cardiomyopathy. This review describes the molecular alterations underlying mitochondrial abnormalities associated with hyperglycemia and discusses their influence on cardiomyocyte viability and function. Based on basic research findings and clinical evidence, diabetic treatment standards and their impact on mitochondrial function, as well as mitochondria-targeted therapies of potential benefit for diabetic cardiomyopathy patients, are also summarized.

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