Integrative Physiology Research Articles

Analysis of Biological Framework and Incorporating Physiological Modelling

Biological frameworks for over the past few decades have been concentrating on the incorporation of medicine and biology including computation and information technology. The present problem is the utility of medical discoveries that have been recorded for over two decades till now: Proteomics and genomics have been projected to develop targeted therapeutically approaches. These approaches are the due to the understanding of the aetiological of the sophisticate illnesses. There are various efforts that are meant to enhance the human physiome based on the evaluation of weaknesses and strengths which will be evaluated in this research. The enhancement of the human framework with validation, documentation and verification of the integrative and underlying feedback is fundamental to project the usable ecosystem. Upcoming developments of the human framework necessitate the integrative physiologists operating in the connection of other scientists. These are some of the scientists with the professionalism in the areas of human biology. These experts are to propose a usable and accurate human framework.

Chitosan-Coated Poly(lactic acid) Nanofibres Loaded with Essential Oils for Wound Healing.

Chronic skin wounds are characterised by a non-healing process that makes necessary the application of wound dressings on the damaged area to promote and facilitate the recovery of skin’s physiological integrity. The aim of the present work is to develop a bioactive dressing that, once applied on the injured tissue, would exert antibacterial activity and promote adhesion and proliferation of fibroblasts. Nanofibres consisting of poly(lactic acid) (PLA) and essential oils (EOs) were electrospun and coated with a medium molecular weight chitosan (CS). Black pepper essential oil (BP-EO) or limonene (L), well-known for their antibacterial properties, were added to the PLA/acetone solution before electrospinning; phase separation phenomena occurred due to the poor solubility of the EOs in the PLA solution and led to fibres having surface nano-pores. The porous electrospun fibres were coated with CS to produce hydrophilic membranes that were easy to handle, biocompatible, and suited to promote cellular proliferation. The fibrous scaffolds were tested in terms of mechanical resistance, wettability, antibacterial activity, in-vitro cytotoxicity, and ability to promote fibroblasts’ adhesion and proliferation. The results obtained proved that the CS coating improved the hydrophilicity of the fibrous mats, enhanced EO’s antibacterial potential, and promoted cell adhesion and proliferation.

Association between physiological performance and short temporal changes in habitat utilisation modulated by environmental factors

Temporal environmental variability causes behavioural and physiological responses in organisms that can affect their spatial location in time, and ultimately drive changes in population and community dynamics. Linking ecological changes with underlying environmental drivers is a complex task that can however be facilitated through the integration of physiology. Our overarching aim was to investigate the association between physiological performance and habitat utilisation patterns modulated by short temporal fluctuations in environmental factors. We used in situ monitoring data from a system experiencing extreme environmental fluctuations over a few hours and we selected four fish species with different habitat utilisation patterns across dissolved oxygen (DO) fluctuations: two commonly observed species (Siganus lineatus and Acanthopagrus pacificus), including at low DO (40 and 50% saturation, respectively), and two reef species (Heniochus acuminatus and Chaetodon vagabundus) never recorded below 70% saturation. We hypothesised that these patterns were associated to species' physiological performance in hypoxia. Therefore, we measured different metabolic variables (O2crit, incipient lethal oxygen (ILO), time to ILO, index of cumulative ambient oxygen deficit (O2deficit), maximum oxygen supply capacity (α)) using respirometry. Physiological performance differed among species and was intrinsically associated to habitat use patterns. S. lineatus had a lower O2crit than H. acuminatus, A. pacificus and C. vagabundus (13, 18.7, 20 and 20.2% saturation respectively). Additionally, S. lineatus and A. pacificus displayed better capacity for survival below O2crit than C. vagabundus and H. acuminatus (lower ILO, higher O2deficit and longer time to ILO) and higher α. Field monitoring data revealed that DO temporarily falls below species’ O2crit and even ILO on most days, suggesting that short temporal variability in DO likely forces species to temporarily avoid harmful conditions, driving important changes in ecosystem structure over a few hours. Our results support the hypothesis that organismal physiology can provide insights into ecological changes occurring over a few hours as a result of environmental variability. Consequently, integrating physiology with ecological data at relevant temporal scales may help predict temporal shifts in ecosystems structure and functions to account for ecological patterns often overlooked and difficult to identify.

Impact of nest sanitation behavior on hosts' egg rejection: an empirical study and meta-analyses.

Egg rejection in birds is a specific adaptation toward avian brood parasitism, whereas nest sanitation is a general behavior for cleaning the nest and avoiding predation. However, both behaviors refer to the action of ejecting objects out of the nest, and nest sanitation has been proposed as a pre-adaptation for egg rejection. Here, we tested the eliciting effect of nest sanitation on egg rejection in the red-whiskered bulbul Pycnonotus jocosus, a potential host species that are sympatric with parasitic cuckoos. We conducted meta-analyses of previous studies on both nest sanitation and egg rejection, in order to evaluate the consistency of our conclusions. Our results showed that nest sanitation did not elicit egg rejection in P. jocosus. The conclusions concerning such an eliciting effect from previous studies were mixed, whereas the methodologies were inconsistent, making the studies unsuitable for comparisons. However, the ejection frequency of nest sanitation was consistently higher than the frequency of egg rejection across different host species or populations. These results suggest that nest sanitation, which is an ancient behavior, is more fundamental than egg rejection, but the effect of the former on the latter is complex and needs further study. Standardized methodologies and the integration of behavior, physiology, and modeling may provide better opportunities to explore the relationship between nest sanitation and egg rejection.

Combined Assessment of Preoperative Frailty and Sarcopenia Allows the Prediction of Overall Survival in Patients with Lung Cancer (NSCLC) and Surgically Treated Brain Metastasis.

Simple SummaryPatients with brain metastasis are at a severe stage of cancer, and brain surgery can prevent neurological morbidity. However, the success of brain surgery might require a patient’s physical integrity prior to the operation. In the present study, we asked whether a preoperative physical decline affects survival in patients with brain metastasis from lung cancer. In order to measure the physical condition, we used a commonly-known index—the so-called frailty index—and additionally measured the thickness of a particular masticatory muscle as muscle loss correlates to physical decline. We found that a decreased muscle thickness was accompanied by worsened survival for patients < 65 years and an increased frailty index correlated to worsened survival for patients ≥ 65 years. These results encourage to use of the frailty index and muscle thickness as easily available parameters in order to more sufficiently estimate individual treatment success in patients with metastatic lung cancer.Neurosurgical resection represents an important therapeutic pillar in patients with brain metastasis (BM). Such extended treatment modalities require preoperative assessment of patients’ physical status to estimate individual treatment success. The aim of the present study was to analyze the predictive value of frailty and sarcopenia as assessment tools for physiological integrity in patients with non-small cell lung cancer (NSCLC) who had undergone surgery for BM. Between 2013 and 2018, 141 patients were surgically treated for BM from NSCLC at the authors’ institution. The preoperative physical condition was assessed by the temporal muscle thickness (TMT) as a surrogate parameter for sarcopenia and the modified frailty index (mFI). For the ≥65 aged group, median overall survival (mOS) significantly differed between patients classified as ‘frail’ (mFI ≥ 0.27) and ‘least and moderately frail’ (mFI < 0.27) (15 months versus 11 months (p = 0.02)). Sarcopenia revealed significant differences in mOS for the <65 aged group (10 versus 18 months for patients with and without sarcopenia (p = 0.036)). The present study confirms a predictive value of preoperative frailty and sarcopenia with respect to OS in patients with NSCLC and surgically treated BM. A combined assessment of mFI and TMT allows the prediction of OS across all age groups.

Occlusal forms and philosophies in full mouth rehabilitation: A literature review

Full mouth rehabilitation encompasses the execution of all the steps necessary to produce healthy, esthetic, well functioning, and self – maintaining masticatory mechanism. The aim is to restore the tooth to its natural form, function and esthetics while maintaining the physiologic integrity in harmonious relationship with the adjacent hard and soft tissues, all of which improves the oral health and quality of life of the patient. It is a complex procedure which involves multiple steps and active participation between prosthodontist, patient and technician to achieve a satisfactory treatment outcome. The apprehension and doubt associated with such procedures are usually associated with an array of available techniques and philosophies. Careful and meticulous diagnosis and formulation of treatment plan holds the key. This article reviews the various occlusal forms, schemes and philosophies associated with Full Mouth Rehabilitation in the existing literature.

Proteomic Analysis of Red Ginseng on Prolonging the Life Span of Male Drosophila melanogaster.

Ginseng (Panax ginseng C. A. Mey.) is a traditional medicine that has been utilized for over 2000 years in Asia and shows varied pharmacological effects. Red ginseng (RG) is steamed and dried ginseng root and is considered to be more effective. Heating inactivates its catabolic enzymes and increases the activities of RG, which can improve the immune system, alleviate fatigue, and has anti-inflammatory effects and antioxidant activity. In addition, RG has a good anti-aging effect, but its mechanism is unclear. Senescence, a side-effect of normal developmental and metabolic processes, is a gradual decline in physiological integrity and function of the body. Senescence is usually associated with a variety of diseases, including neurodegenerative diseases and diabetes. Research on anti-aging and the prolongation of life span has always been a focus topic. In this study, we investigated the molecular mechanism of RG that results in prolonged the life span for male Drosophila melanogaster. Isobaric tag for relative and absolute quantitation (iTRAQ) was used to identify protein changes in an old male D. melanogaster treated with RG. The differential proteins were verified by qRT-PCR and western blotting. The results showed that 12.5 mg/ml RG prolonged its life span significantly. iTRAQ results showed that, compared to the control group, 32 upregulated proteins and 62 downregulated proteins displayed significantly differential expression in the RG group. In this study, we explored the pathways that RG may participate in that extend the life span of D. melanogaster, and the results showed that the PI3K/AKT/FoxO pathway was involved. In addition, 4E-BP increased and participated in the regulation of life span.

Pharyngoesophageal motility reflex mechanisms in the human neonate: importance of integrative cross-systems physiology.

Swallowing is a critical function for survival and development in human neonates and requires cross-system coordination between neurological, airway, and digestive motility systems. Development of pharyngoesophageal motility is influenced by intra- and extrauterine development, pregnancy complications, and neonatal comorbidities. The primary role of these motility reflex mechanisms is to maintain aerodigestive homeostasis under basal and adaptive biological conditions including oral feeding, gastroesophageal reflux, and sleep. Failure may result in feeding difficulties, airway compromise, dysphagia, aspiration syndromes, and chronic eating difficulties requiring prolonged tube feeding. We review the integration of cross-systems physiology to describe the basis for physiological and pathophysiological neonatal aerodigestive functions.

Multi-domain probiotic consortium as an alternative to chemical remediation of oil spills at coral reefs and adjacent sites

BackgroundBeginning in the last century, coral reefs have suffered the consequences of anthropogenic activities, including oil contamination. Chemical remediation methods, such as dispersants, can cause substantial harm to corals and reduce their resilience to stressors. To evaluate the impacts of oil contamination and find potential alternative solutions to chemical dispersants, we conducted a mesocosm experiment with the fire coral Millepora alcicornis, which is sensitive to environmental changes. We exposed M. alcicornis to a realistic oil-spill scenario in which we applied an innovative multi-domain bioremediator consortium (bacteria, filamentous fungi, and yeast) and a chemical dispersant (Corexit® 9500, one of the most widely used dispersants), to assess the effects on host health and host-associated microbial communities.Results The selected multi-domain microbial consortium helped to mitigate the impacts of the oil, substantially degrading the polycyclic aromatic and n-alkane fractions and maintaining the physiological integrity of the corals. Exposure to Corexit 9500 negatively impacted the host physiology and altered the coral-associated microbial community. After exposure, the abundances of certain bacterial genera such as Rugeria and Roseovarius increased, as previously reported in stressed or diseased corals. We also identified several bioindicators of Corexit 9500 in the microbiome. The impact of Corexit 9500 on the coral health and microbial community was far greater than oil alone, killing corals after only 4 days of exposure in the flow-through system. In the treatments with Corexit 9500, the action of the bioremediator consortium could not be observed directly because of the extreme toxicity of the dispersant to M. alcicornis and its associated microbiome.Conclusions Our results emphasize the importance of investigating the host-associated microbiome in order to detect and mitigate the effects of oil contamination on corals and the potential role of microbial mitigation and bioindicators as conservation tools. Chemical dispersants were far more damaging to corals and their associated microbiome than oil, and should not be used close to coral reefs. This study can aid in decision-making to minimize the negative effects of oil and dispersants on coral reefs.28o34xjp3LHKa34vd8g18TVideo abstract

Breath-Hold Diving – The Physiology of Diving Deep and Returning

Breath-hold diving involves highly integrative physiology and extreme responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure. With astonishing depth records exceeding 100 m, and up to 214 m on a single breath, the human capacity for deep breath-hold diving continues to refute expectations. The physiological challenges and responses occurring during a deep dive highlight the coordinated interplay of oxygen conservation, exercise economy, and hyperbaric management. In this review, the physiology of deep diving is portrayed as it occurs across the phases of a dive: the first 20 m; passive descent; maximal depth; ascent; last 10 m, and surfacing. The acute risks of diving (i.e., pulmonary barotrauma, nitrogen narcosis, and decompression sickness) and the potential long-term medical consequences to breath-hold diving are summarized, and an emphasis on future areas of research of this unique field of physiological adaptation are provided.

Acer Truncatum Seed Oil Alleviates Learning and Memory Impairments of Aging Mice

Aging, characterized by a time-dependent functional decline of physiological integrity, is the major independent risk factor for many neurodegeneration diseases. Therefore, it’s necessary to look for natural food supplements to extend the healthy lifespan of aging people. We here treated normal aging mice with acer truncatum seed oil, and found that the seed oil significantly improved the learning and memory ability. Proteomics revealed that the seed oil administration changed many proteins expression involving in biological processes, including complement and coagulation cascades, inflammatory response pathway and innate immune response. BDNF/TrkB signaling pathway was also activated by acer truncatum seed oil treatment. And the seed oil administration increased the expression of postsynaptic related proteins including PSD95, GluA1, and NMDAR1, and decreased the mRNA level of inflammatory factors containing IL-1β, TNF-α, and IL-6. These findings suggest that acer truncatum seed oil holds a promise as a therapeutic food supplement for delaying aging with multiple mechanisms.

The Pitfalls of in vivo Cardiac Physiology in Genetically Modified Mice - Lessons Learnt the Hard Way in the Creatine Kinase System.

In order to fully understand gene function, at some point, it is necessary to study the effects in an intact organism. The creation of the first knockout mouse in the late 1980’s gave rise to a revolution in the field of integrative physiology that continues to this day. There are many complex choices when selecting a strategy for genetic modification, some of which will be touched on in this review, but the principal focus is to highlight the potential problems and pitfalls arising from the interpretation of in vivo cardiac phenotypes. As an exemplar, we will scrutinize the field of cardiac energetics and the attempts to understand the role of the creatine kinase (CK) energy buffering and transport system in the intact organism. This story highlights the confounding effects of genetic background, sex, and age, as well as the difficulties in interpreting knockout models in light of promiscuous proteins and metabolic redundancy. It will consider the dose-dependent effects and unintended consequences of transgene overexpression, and the need for experimental rigour in the context of in vivo phenotyping techniques. It is intended that this review will not only bring clarity to the field of cardiac energetics, but also aid the non-expert in evaluating and critically assessing data arising from in vivo genetic modification.

112 Chronic sleep restriction disrupts slow-wave sleep homeostatic regulation and damages monoaminergic structures in the rat brain

Abstract Introduction The neurophysiological mechanisms underlying long-term neurological and cognitive disorders associated with chronic sleep restriction (CSR) are not fully understood. Here we evaluated how the sleep-wake cycle changes during and after a period of sleep restriction in rats, and whether CSR results in neurodegeneration in monoaminergic brain structures. Methods For CSR, 7-8-month-old Wistar rats underwent cycles of 3 h of sleep deprivation (SD) and 1 h of sleep opportunity (SO) continuously for 5 days on the orbital shaker. Telemetric sleep recordings were made before, during, and after CSR. Neurodegeneration in brain monoaminergic structures was assessed immunohistochemically. Results During SD, wakefulness comprised 85% of the total registration time; the remaining time was represented by drowsiness with low EEG delta power. Rapid eye movement sleep (REMS) was absent. During CSR, slow-wave sleep (SWS) and REMS were reduced by 62% and 57%. Total SWS time during SO periods increased on the first CSR day, but decreased to the baseline by the fifth CSR day. SWS EEG delta power (a measure of sleep intensity) decreased gradually from the first to the fifth CSR day. REMS total time remained elevated during all SO periods. During the first recovery day after CSR, SWS did not change, but REMS increased by 30%. No changes in total sleep time were found on the second recovery day but sleep intensity was decreased. In 14 days after CSR, all sleep parameters returned to the baseline. We revealed a loss of 24% of noradrenergic locus coeruleus neurons, 29% and 17% of dopaminergic neurons in the substantia nigra, the ventral tegmental area as well as in their striatal terminals. Conclusion We consider CSR as a damaging factor leading to a gradual suppression of homeostatic mechanisms governing sleep recovery. CSR can provoke neurodegeneration in monoaminergic structures involved in the regulation of emotional behavior, sleep, and autonomic functions. Support (if any) Ministry of Science and Higher Education of the Russian Federation grant (No. 075-15-2020-916 dated November 13, 2020) for the establishment and development of the Pavlovsky Center “Integrative Physiology for Medicine, High-Tech Healthcare and Stress Resilience Technologies”.

Corrigendum for Cui J et al., volume 317, 2019, p. R280–R288

CorrigendumCorrigendum for Cui J et al., volume 317, 2019, p. R280–R288Published Online:04 May 2021https://doi.org/10.1152/ajpregu.00293.2018_COROriginal articleMoreSectionsPDF (98 KB)Download PDFDownload PDFPlus ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmail Cui J, Drew RC, Muller MD, Blaha C, Gonzalez V, Sinoway LI. Habitual cigarette smoking raises pressor responses to spontaneous bursts of muscle sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 317: R280-R288. First published July 24, 2019; doi:10.1152/ajpregu.00293.2018.On p. R287, there was an error in GRANTS. The corrected version is shown below:This study was supported by the American Heart Association Grant 15GRNT24480051 (to J. Cui) and the National Institutes of Health Grant UL1 TR-002014 (to L. I. Sinoway).This article has no references to display. Previous Back to Top Next FiguresReferencesRelatedInformationRelated articlesHabitual cigarette smoking raises pressor responses to spontaneous bursts of muscle sympathetic nerve activity 24 Jul 2019American Journal of Physiology-Regulatory, Integrative and Comparative Physiology More from this issue > Volume 320Issue 5May 2021Pages R714-R714 Crossmark Copyright & PermissionsCopyright © 2021 the American Physiological Societyhttps://doi.org/10.1152/ajpregu.00293.2018_CORPubMed33945336History Published online 4 May 2021 Published in print 1 May 2021 PDF download Metrics Downloaded 249 times

Tracking of Individual Motor Units Following Concentric and Eccentric Exercise‐induced Fatigue Reveals Contraction‐type Specific Changes in Discharge Properties

Muscle fatigue is characterised by a reduction in force output, with increases in force production partly mediated by adjustments in motor unit (MU) firing properties. Conflicting research has found MU firing rate (FR) to both increase and decrease following fatiguing exercise and this disparity may be influenced by contraction type. Using high density surface electromyography (HD-EMG) we have previously reported a decrease in FR following concentric (CON), and an increase following eccentric (ECC) contractions (1). However, HD-EMG also enables the tracking of individual MUs across tasks (2), potentially revealing more detailed MU-specific adaptations to fatigue. The aims of this study were to track the FR of individual MUs following CON and ECC contractions of the vastus lateralis (VL) muscle. HD-EMG was used to identify individual MU potentials (MUPs) from the VLs of 8 young volunteers (4 females; 21 ± 0.5 years). All MUPs were recorded during 4 sustained isometric contractions held at a target line of 25 and 40% of the participants maximum voluntary contraction (MVC) before and after completing CON and ECC fatiguing exercise (CON: ‘stepping up’ with one leg, ECC: ‘stepping down’ on the other leg, wearing a weighted vest +25-40% body weight). The coefficient of variation of force was calculated to assess force steadiness (FS). A total of 43 MUs were tracked pre and post fatigue. Paired t-tests were used for comparisons of tracked MUs. Significance was assumed when p<0.05. MVC decreased in both CON and ECC legs post exercise (-15.3% and -21.1% respectively; p<0.01) and EMG root-mean square amplitude (RMS) significantly decreased in both legs after fatigue (both p≤0.001). FS deteriorated in ECC only at both 25% and 40% MVC (p=0.004 and p=0.04 respectively), with no change in CON. Data from individual tracked MUs supported our previous finding with a decreased FR following CON (-4.7%; p=0.037) but no difference in FR with ECC (+6.9%; p=0.168). These data demonstrate that motor control and MU FR following exercise-induced fatigue differ according to exercise modality. HD-EMG enables specific changes in single motor units to be studied across sessions in addition to the overall MU population effects, and here the FR did not change following ECC exercise even with a notably reduced absolute force (21%). The possibility of differential MU recruitment strategies compensating for discharge characteristics and impacting motor control requires further investigation as this may have translational relevance in ageing, neuromuscular conditions and for post-exercise recovery from fatigue. 1. Jones EJ, Martinez-Valdes E, Negro F, McCormick D, Atherton PJ, Phillips BE, et al. Motor unit discharge properties following concentric and eccentric exercise-induced fatigue are dependent upon contraction type. American Physiological Society: Integrative Physiology of Exercise. 2020. 2. Martinez-Valdes E, Negro F, Falla D, Dideriksen JL, Heckman C, Farina D. Inability to increase the neural drive to muscle is associated with task failure during submaximal contractions. J Neurophysiol. 2020.

EFEK KATEKIN DAUN GAMBIR (UNCARIA GAMBIR ROXB) TERHADAP KADAR MALONDIALDEHID SERUM DAN EKSPRESI GEN SIRTUIN 1 PADA HIPOKAMPUS MENCIT BETINA MODEL PENUAAN

Aging is a physiological process characterized by progressive loss of physiological integrity that leads to impaired function and increased susceptibility to death. Oxidative stress is one of the factors that cause aging due to an imbalance between the amount of oxidants and antioxidants. In oxidative stress condition, malondialdehyde levels increase. D-galactose can induce aging in various organ systems. D-galactose induces oxidative stress in various organs through increased production of reactive oxygen species (ROS) and advanced glycation endproducts. In oxidative stress condition, sirtuin1 (Sirt1) produces ribose O-acetyl-ADP which, later, is reduced into ribose ADP. Both of them have a protective effect against oxidative stress. Consumption of antioxidants may prevent aging. Gambir contains health-promoting ingredients such as catechins. This study aims to determine the effect of gambier leaves catechin extract on serum malondialdehyde levels and the expression of sirtuin 1 gene in female mice aging model induced by d-galactose. This is an in vivo experiment with post test-only control group study. The samples were 28 female mice which were divided into 4 groups namely P0, P1, P2, and P3. Each group was injected 150 mg/kgBW d-galactose intraperitoneally. P1, P2, and P3 were treated orally with 100, 200, and 400 mg/kgBW gambir leaves catechin extract, respectively. Statistical test use descriftive analisys. There were significant differences in serum MDA levels in all groups (p=0.002) and there were significant differences between the P0 and P2 groups (p=0.010) and between the P0 and P3 groups (p=0.010). Sirtuin1 gene relative expressions decresead in P1 (0,49), P2 (0,74), and P3 (0,43) as compared to P0 (1.00). Conclusion. Gambir leaves catechin extract reduces serum malondialdehyde levels in aging mouse models induced by d-galactose with an optimal dose of 200mg/kgBW. and cannot reduce the relative expression of Sirt1

Polystyrene microplastics-induced ROS overproduction disrupts the skeletal muscle regeneration by converting myoblasts into adipocytes

The environmental problem of Microplastics (MPs) pollution poses a great threat to human and animal health, which has attracted global attention. The physiological integrity of skeletal muscle is extremely important for the survival of animals. Here, we investigated the effect of two size polystyrene microplastics (PS-MPs, 1–10 µm and 50–100 µm) on the growth of anterior tibial (TA) muscle and repair after injury in mice. Results showed that the regeneration of skeletal muscle was delayed by PS-MPs exposure and was negatively correlated with particle size. H&E staining and Oil red O staining showed that PS-MPs exposure reduced the average cross-sectional area (CSA) and diameter of the muscle fibers, increased lipid deposition. Further mechanistic research displayed that though PS-MPs treatment did not affect cell viability of myoblast, it aggravated intracellular ROS generation and oxidative stress, inhibited myogenic differentiation by decreasing the phosphorylation of p38 MAPK, and promote adipogenic differentiation by increasing the expression of NF-κB, which could be alleviated by NAC. In brief, our data demonstrated that the ROS overproduction caused by PS-MPs disturbed the regeneration of skeletal muscle and directed the fate of satellite cells in mice.

Effects of resource sharing directionality on physiologically integrated clones of the invasive Carpobrotus edulis

Abstract Aims One of the key traits associated with clonal growth in plants is the capacity for physiological integration, which allows resource sharing between connected ramets within a clonal system. Resource transport is expected to occur following a source–sink relationship: from ramets established in rich patches to ramets growing in poor patches. However, some experiments have shown that acropetal transport (from basal to apical modules) usually exceeds basipetal transport (from apical to basal ramets). In this study, we aimed to determine the resource transport directionality in physiologically integrated modules of the invader Carpobrotus edulis. Methods We conducted two manipulative experiments under common garden conditions that studied the effect of different nutrient levels located at different positions (basal, medial and apical) on connected and disconnected clonal systems of C. edulis. We compared the biomass partitioning patterns and final biomass of ramets to elucidate whether the effect of physiological integration is affected by the directionality of the resource transport. Important Findings Results indicate a prevalent acropetal transport of resources in C. edulis, with a developmentally programmed division of labor where basal ramets were specialized in obtaining soil-based resources and apical ramets specialized in aboveground growth. This biomass partitioning pattern was not affected by the nutrient conditions in which basal or apical ramets were growing, although the highest benefit was achieved by apical ramets growing under the most stressed conditions. This developmentally programmed division of labor is expected to increase the lateral growth of C. edulis, and therefore could have meaningful implications for the expansion of this invasive species.

In vitro and in vivo characterisation of senescence markers in osteoarthritis

Purpose: Osteoarthritis (OA) is the most prevalent osteoarticular disease and a major cause of disability in aging adult. OA is characterized by cartilage breakdown, synovial inflammation, osteophyte formation, and subchondral bone remodelling. While OA is associated with a huge societal and economic burden, no efficient disease-modifying drug still exists today. In addition to obesity, metabolic disorders, and trauma, one of the major risks of OA is ageing. Ageing is a complex physiological process that relates to a gradual decline in certain functions, coordination, loss of homeostasis, and physiological integrity.

Oral administration of repurposed drug targeting Cyp46A1 increases survival times of prion infected mice

Prion diseases are fatal, infectious, and incurable neurodegenerative disorders caused by misfolding of the cellular prion protein (PrPC) into the infectious isoform (PrPSc). In humans, there are sporadic, genetic and infectious etiologies, with sporadic Creutzfeldt-Jakob disease (sCJD) being the most common form. Currently, no treatment is available for prion diseases. Cellular cholesterol is known to impact prion conversion, which in turn results in an accumulation of cholesterol in prion-infected neurons. The major elimination of brain cholesterol is achieved by the brain specific enzyme, cholesterol 24-hydroxylase (CYP46A1). Cyp46A1 converts cholesterol into 24(S)-hydroxycholesterol, a membrane-permeable molecule that exits the brain. We have demonstrated for the first time that Cyp46A1 levels are reduced in the brains of prion-infected mice at advanced disease stage, in prion-infected neuronal cells and in post-mortem brains of sCJD patients. We have employed the Cyp46A1 activator efavirenz (EFV) for treatment of prion-infected neuronal cells and mice. EFV is an FDA approved anti-HIV medication effectively crossing the blood brain barrier and has been used for decades to chronically treat HIV patients. EFV significantly mitigated PrPSc propagation in prion-infected cells while preserving physiological PrPC and lipid raft integrity. Notably, oral administration of EFV treatment chronically at very low dosage starting weeks to months after intracerebral prion inoculation of mice significantly prolonged the lifespan of animals. In summary, our results suggest that Cyp46A1 as a novel therapeutic target and that its activation through repurposing the anti-retroviral medication EFV might be valuable treatment approach for prion diseases.