Showing papers in "Frontiers in Physiology in 2023"

Mitigating challenges and expanding the future of vascular tissue engineering—are we there yet?

Abstract: Atherosclerosis is still a significant cause of death in western societies. The leading cause of this cardiovascular disease is lipid accumulation and inflammation of the large arteries, which may lead to clinical complications such as arterial thrombosis, myocardial infarction, and ischemic stroke (Xenotransplantation, 1997). Drugs are usually the first treatment choice, even in the late stages of atherosclerosis. Sometimes, more aggressive treatment like Coronary artery bypass surgery (CABG) is needed. CABGs are performed by harvesting a vessel from the patient, but the patient undergoing two surgeries only added to their comorbidities. However, long-term results after CABG depend not only on the completeness of revascularization and the initial severity of coronary and myocardial lesions but also on comorbidities like diabetes mellitus, arterial hypertension, and pulmonary and renal disorders. Moreover, the limited availability of autografts was soon realized, and new options proposed by tissue engineering were started exploring to design synthetic grafts (Corridon et al., 2013). Vascular tissue engineering (VTE) is focused on constructing vessels using different biomaterials, cell sources, biomolecules, and mechanical stimuli that can function in physiological environments (Lovett et al., 2009; Pradeep et al., 2019; Wang et al., 2022a). Such vessels replace non-functional vascular compartments and generate networks within bio (artificial) scaffolds. Pioneering efforts in this field date back to 1950, when artificial vascular grafts made from synthetic polymer materials were used to replace occluded arterial vessels (Song et al., 2018). It was perceived that biomaterials could support microvascular function showing great potential in accelerating the transition away from xenogenic materials for clinical application. For example, Li et al. (2017) developed a hyaluronic acid-based hydrogel chemically modified with fibronectin motifs that promote EC binding of α3/α5 b1 integrins, resulting in better vascularization to a non-modified hydrogel in a mouse stroke model. Similarly, advances in nanotechnology can bring additional functionality to vascular scaffolds, optimize internal vascular graft surface, reduce early thrombosis and inflammatory responses, and even direct the differentiation of stem cells into the vascular cell phenotype (Mironov et al., 2008; Wang et al., 2022a). OPEN ACCESS

Virtual Fly Brain—An interactive atlas of the Drosophila nervous system

Abstract: As a model organism, Drosophila is uniquely placed to contribute to our understanding of how brains control complex behavior. Not only does it have complex adaptive behaviors, but also a uniquely powerful genetic toolkit, increasingly complete dense connectomic maps of the central nervous system and a rapidly growing set of transcriptomic profiles of cell types. But this also poses a challenge: Given the massive amounts of available data, how are researchers to Find, Access, Integrate and Reuse (FAIR) relevant data in order to develop an integrated anatomical and molecular picture of circuits, inform hypothesis generation, and find reagents for experiments to test these hypotheses? The Virtual Fly Brain (virtualflybrain.org) web application & API provide a solution to this problem, using FAIR principles to integrate 3D images of neurons and brain regions, connectomics, transcriptomics and reagent expression data covering the whole CNS in both larva and adult. Users can search for neurons, neuroanatomy and reagents by name, location, or connectivity, via text search, clicking on 3D images, search-by-image, and queries by type (e.g., dopaminergic neuron) or properties (e.g., synaptic input in the antennal lobe). Returned results include cross-registered 3D images that can be explored in linked 2D and 3D browsers or downloaded under open licenses, and extensive descriptions of cell types and regions curated from the literature. These solutions are potentially extensible to cover similar atlasing and data integration challenges in vertebrates.

Enhancing the expression of a key mitochondrial enzyme at the inception of ischemia-reperfusion injury can boost recovery and halt the progression of acute kidney injury

Abstract: Hydrodynamic fluid delivery has shown promise in influencing renal function in disease models. This technique provided pre-conditioned protection in acute injury models by upregulating the mitochondrial adaptation, while hydrodynamic injections of saline alone have improved microvascular perfusion. Accordingly, hydrodynamic mitochondrial gene delivery was applied to investigate the ability to halt progressive or persistent renal function impairment following episodes of ischemia-reperfusion injuries known to induce acute kidney injury (AKI). The rate of transgene expression was approximately 33% and 30% in rats with prerenal AKI that received treatments 1 (T1hr) and 24 (T24hr) hours after the injury was established, respectively. The resulting mitochondrial adaptation via exogenous IDH2 (isocitrate dehydrogenase 2 (NADP+) and mitochondrial) significantly blunted the effects of injury within 24 h of administration: decreased serum creatinine (≈60%, p < 0.05 at T1hr; ≈50%, p < 0.05 at T24hr) and blood urea nitrogen (≈50%, p < 0.05 at T1hr; ≈35%, p < 0.05 at T24hr) levels, and increased urine output (≈40%, p < 0.05 at T1hr; ≈26%, p < 0.05 at T24hr) and mitochondrial membrane potential, Δψm, (≈ by a factor of 13, p < 0.001 at T1hr; ≈ by a factor of 11, p < 0.001 at T24hr), despite elevated histology injury score (26%, p < 0.05 at T1hr; 47%, p < 0.05 at T24hr). Therefore, this study identifies an approach that can boost recovery and halt the progression of AKI at its inception.

Sex differences in stretch-induced hypertrophy, maximal strength and flexibility gains

Abstract: Introduction: If the aim is to increase maximal strength (MSt) and muscle mass, resistance training (RT) is primarily used to achieve these outcomes. However, research indicates that long-duration stretching sessions of up to 2 h per day can also provide sufficient stimuli to induce muscle growth. In RT literature, sex-related differences in adaptations are widely discussed, however, there is a lack of evidence addressing the sex-related effects on MSt and muscle thickness (MTh) of longer duration stretch training. Therefore, this study aimed to investigate the effects of 6 weeks of daily (1 h) unilateral static stretch training of the plantar flexors using a calf-muscle stretching device. Methods: Fifty-five healthy (m = 28, f = 27), active participants joined the study. MSt and range of motion (ROM) were measured with extended and flexed knee joint, and MTh was investigated in the medial and lateral heads of the gastrocnemius. Results: Statistically significant increases in MSt of 6%–15% (p < .001–.049, d = 0.45–1.09), ROM of 6%–21% (p < .001–.037, d = 0.47–1.38) and MTh of 4%–14% (p < .001–.005, d = 0.46–0.72) from pre-to post-test were observed, considering both sexes and both legs. Furthermore, there was a significant higher increase in MSt, MTh and ROM in male participants. In both groups, participants showed more pronounced adaptations in MSt and ROM with an extended knee joint as well as MTh in the medial head of the gastrocnemius (p < .001–.047). Results for relative MSt increases showed a similar result (p < .001–.036, d = 0.48–1.03). Discussion: Results are in accordance with previous studies pointing out significant increases of MSt, MTh and ROM due to long duration static stretch training. Both sexes showed significant increases in listed parameters however, male participants showed superior increases.

Blood pressure stratification using photoplethysmography and light gradient boosting machine

Abstract: Introduction: Globally, hypertension (HT) is a substantial risk factor for cardiovascular disease and mortality; hence, rapid identification and treatment of HT is crucial. In this study, we tested the light gradient boosting machine (LightGBM) machine learning method for blood pressure stratification based on photoplethysmography (PPG), which is used in most wearable devices. Methods: We used 121 records of PPG and arterial blood pressure (ABP) signals from the Medical Information Mart for Intensive Care III public database. PPG, velocity plethysmography, and acceleration plethysmography were used to estimate blood pressure; the ABP signals were used to determine the blood pressure stratification categories. Seven feature sets were established and used to train the Optuna-tuned LightGBM model. Three trials compared normotension (NT) vs. prehypertension (PHT), NT vs. HT, and NT + PHT vs. HT. Results: The F1 scores for these three classification trials were 90.18%, 97.51%, and 92.77%, respectively. The results showed that combining multiple features from PPG and its derivative led to a more accurate classification of HT classes than using features from only the PPG signal. Discussion: The proposed method showed high accuracy in stratifying HT risks, providing a noninvasive, rapid, and robust method for the early detection of HT, with promising applications in the field of wearable cuffless blood pressure measurement.

Sugar perception in honeybees

Abstract: Honeybees (Apis mellifera) need their fine sense of taste to evaluate nectar and pollen sources. Gustatory receptors (Grs) translate taste signals into electrical responses. In vivo experiments have demonstrated collective responses of the whole Gr-set. We here disentangle the contributions of all three honeybee sugar receptors (AmGr1-3), combining CRISPR/Cas9 mediated genetic knock-out, electrophysiology and behaviour. We show an expanded sugar spectrum of the AmGr1 receptor. Mutants lacking AmGr1 have a reduced response to sucrose and glucose but not to fructose. AmGr2 solely acts as co-receptor of AmGr1 but not of AmGr3, as we show by electrophysiology and using bimolecular fluorescence complementation. Our results show for the first time that AmGr2 is indeed a functional receptor on its own. Intriguingly, AmGr2 mutants still display a wildtype-like sugar taste. AmGr3 is a specific fructose receptor and is not modulated by a co-receptor. Eliminating AmGr3 while preserving AmGr1 and AmGr2 abolishes the perception of fructose but not of sucrose. Our comprehensive study on the functions of AmGr1, AmGr2 and AmGr3 in honeybees is the first to combine investigations on sugar perception at the receptor level and simultaneously in vivo. We show that honeybees rely on two gustatory receptors to sense all relevant sugars.

Mapping the lymphatic system across body scales and expertise domains: A report from the 2021 National Heart, Lung, and Blood Institute workshop at the Boston Lymphatic Symposium

Abstract: Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.

Reliability of pathophysiological markers reflective of exercise-induced gastrointestinal syndrome (EIGS) in response to 2-h high-intensity interval exercise: A comprehensive methodological efficacy exploration

Abstract: The study aimed to determine the test-retest reliability of exercise-induced gastrointestinal syndrome (EIGS) biomarkers, and assess the association of pre-exercise short chain fatty acid (SCFA) concentration with these biomarkers in response to prolonged strenuous exercise. Thirty-four participants completed 2 h of high-intensity interval training (HIIT) on two separate occasions with at least 5-days washout. Blood samples were collected pre- and post-exercise, and analysed for biomarkers associated with EIGS [i.e., cortisol, intestinal fatty-acid binding protein (I-FABP), sCD14, lipopolysaccharide binding protein (LBP), leukocyte counts, in-vitro neutrophil function, and systemic inflammatory cytokine profile]. Fecal samples were collected pre-exercise on both occasions. In plasma and fecal samples, bacterial DNA concentration was determined by fluorometer quantification, microbial taxonomy by 16S rRNA amplicon sequencing, and SCFA concentration by gas-chromatography. In response to exercise, 2 h of HIIT modestly perturbed biomarkers indicative of EIGS, including inducing bacteremia (i.e., quantity and diversity). Reliability analysis using comparative tests, Cohen’s d, two-tailed correlation, and intraclass correlation coefficient (ICC) of resting biomarkers presented good-to-excellent for IL-1ra (r = 0.710, ICC = 0.92), IL-10 (r = 0.665, ICC = 0.73), cortisol (r = 0.870, ICC = 0.87), and LBP (r = 0.813, ICC = 0.76); moderate for total (r = 0.839, ICC = 0.44) and per cell (r = 0.749, ICC = 0.54) bacterially-stimulated elastase release, IL-1β (r = 0.625, ICC = 0.64), TNF-α (r = 0.523, ICC = 0.56), I-FABP (r = 0.411, ICC = 0.21), and sCD14 (r = 0.409, ICC = 0.38), plus fecal bacterial α-diversity; and poor for leukocyte (r = 0.327, ICC = 0.33) and neutrophil (r = 0.352, ICC = 0.32) counts. In addition, a medium negative correlation was observed between plasma butyrate and I-FABP (r = −0.390). The current data suggest a suite of biomarkers should be used to determine the incidence and severity of EIGS. Moreover, determination of plasma and/or fecal SCFA may provide some insight into the mechanistic aspects of EIGS instigation and magnitude in response to exercise.

Cortex-specific transcriptome profiling reveals upregulation of interferon-regulated genes after deeper cerebral hypoperfusion in mice

Abstract: Background: Chronic cerebral hypoperfusion (CCH) is commonly accompanied by brain injury and glial activation. In addition to white matter lesions, the intensity of CCH greatly affects the degree of gray matter damage. However, little is understood about the underlying molecular mechanisms related to cortical lesions and glial activation following hypoperfusion. Efforts to investigate the relationship between neuropathological alternations and gene expression changes support a role for identifying novel molecular pathways by transcriptomic mechanisms. Methods: Chronic cerebral ischemic injury model was induced by the bilateral carotid artery stenosis (BCAS) using 0.16/0.18 mm microcoils. Cerebral blood flow (CBF) was evaluated using laser speckle contrast imaging (LSCI) system. Spatial learning and memory were assessed by Morris water maze test. Histological changes were evaluated by Hematoxylin staining. Microglial activation and neuronal loss were further examined by immunofluorescence staining. Cortex-specific gene expression profiling analysis was performed in sham and BCAS mice, and then validated by quantitative RT-PCR and immunohistochemistry (IHC). Results: In our study, compared with the sham group, the right hemisphere CBF of BCAS mice decreased to 69% and the cognitive function became impaired at 4 weeks postoperation. Besides, the BCAS mice displayed profound gray matter damage, including atrophy and thinning of the cortex, accompanied by neuronal loss and increased activated microglia. Gene set enrichment analysis (GSEA) revealed that hypoperfusion-induced upregulated genes were significantly enriched in the pathways of interferon (IFN)-regulated signaling along with neuroinflammation signaling. Ingenuity pathway analysis (IPA) predicted the importance of type I IFN signaling in regulating the CCH gene network. The obtained RNA-seq data were validated by qRT-PCR in cerebral cortex, showing consistency with the RNA-seq results. Also, IHC staining revealed elevated expression of IFN-inducible protein in cerebral cortex following BCAS-hypoperfusion. Conclusion: Overall, the activation of IFN-mediated signaling enhanced our understanding of the neuroimmune responses induced by CCH. The upregulation of IFN-regulated genes (IRGs) might exert a critical impact on the progression of cerebral hypoperfusion. Our improved understanding of cortex-specific transcriptional profiles will be helpful to explore potential targets for CCH.

The return from underperformance to sustainable world-class level: A case study of a male cross-country skier

Abstract: Purpose: To determine the main factors associated with unexpected underperformance and prospectively describe the holistic process of returning to sustainable world-class level in a male cross-country skier. Methods: Longitudinal training data was retrospectively analyzed across nine seasons (2012-2013 to 2020-2021), and categorized into training forms (endurance, strength, and speed), intensities [low- (LIT), moderate- (MIT), and high-intensity training (HIT)], and modes (specific and non-specific). Performance data was obtained from the International Ski and Snowboard Federation. Following two seasons of unexpected underperformance (2019-2020 and 2020-2021), the participant was prospectively followed in the process of returning to sustainable world-class level (2021-2022). Day-to-day training data and physiological tests were analyzed, and interviews with the participant and the head coach conducted. Results: Longitudinal training data from 2012-2013 to 2018-2019 demonstrated a non-linear 30% increase in total training volume (from 772 to 1,002 h), mainly caused by increased volume of ski-specific endurance training without changes in intensity distribution. Coincidingly, the participant gradually reached a world-class performance level. After two seasons of unexpected underperformance with relatively similar training volumes and intensity distributions as in the preceding seasons, the possible contributing factors were identified: lack of training periodization, limited monitoring and intensity control, particularly in connection with a “extreme” regime of training with low carbohydrate availability and days including two MIT sessions, as well as lack of systematic technique training and follow-up by coaches on a daily basis. Consequently, the return to world-class level included the introduction of a clear micro-cycle periodization, more systematic physiological monitoring and testing, more accurate intensity control, increased carbohydrate intake during and between sessions, as well as increased emphasize on technique training and an assistant coach present during day-to-day training. Conclusion: These longitudinal data describe the main factors leading to unexpected underperformance, in addition to providing unique insights into the corresponding process of returning to sustainable world-class level in a male cross-country skier. The holistic approach described in this case study may serve as a theoretical framework for future studies and practical work with underperforming endurance athletes.

Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer’s disease

Abstract: The heart is a functional syncytium controlled by a delicate and sophisticated balance ensured by the tight coordination of its several cell subpopulations. Accordingly, cardiomyocytes together with the surrounding microenvironment participate in the heart tissue homeostasis. In the right atrium, the sinoatrial nodal cells regulate the cardiac impulse propagation through cardiomyocytes, thus ensuring the maintenance of the electric network in the heart tissue. Notably, the central nervous system (CNS) modulates the cardiac rhythm through the two limbs of the autonomic nervous system (ANS): the parasympathetic and sympathetic compartments. The autonomic nervous system exerts non-voluntary effects on different peripheral organs. The main neuromodulator of the Sympathetic Nervous System (SNS) is norepinephrine, while the principal neurotransmitter of the Parasympathetic Nervous System (PNS) is acetylcholine. Through these two main neurohormones, the ANS can gradually regulate cardiac, vascular, visceral, and glandular functions by turning on one of its two branches (adrenergic and/or cholinergic), which exert opposite effects on targeted organs. Besides these neuromodulators, the cardiac nervous system is ruled by specific neuropeptides (neurotrophic factors) that help to preserve innervation homeostasis through the myocardial layers (from epicardium to endocardium). Interestingly, the dysregulation of this neuro-signaling pathway may expose the cardiac tissue to severe disorders of different etiology and nature. Specifically, a maladaptive remodeling of the cardiac nervous system may culminate in a progressive loss of neurotrophins, thus leading to severe myocardial denervation, as observed in different cardiometabolic and neurodegenerative diseases (myocardial infarction, heart failure, Alzheimer’s disease). This review analyzes the current knowledge on the pathophysiological processes involved in cardiac nervous system impairment from the perspectives of both cardiac disorders and a widely diffused and devastating neurodegenerative disorder, Alzheimer’s disease, proposing a relationship between neurodegeneration, loss of neurotrophic factors, and cardiac nervous system impairment. This overview is conducive to a more comprehensive understanding of the process of cardiac neuro-signaling dysfunction, while bringing to light potential therapeutic scenarios to correct or delay the adverse cardiovascular remodeling, thus improving the cardiac prognosis and quality of life in patients with heart or neurodegenerative disorders.

Airway remodeling heterogeneity in asthma and its relationship to disease outcomes

Abstract: Asthma affects an estimated 262 million people worldwide and caused over 461,000 deaths in 2019. The disease is characterized by chronic airway inflammation, reversible bronchoconstriction, and airway remodeling. Longitudinal studies have shown that current treatments for asthma (inhaled bronchodilators and corticosteroids) can reduce the frequency of exacerbations, but do not modify disease outcomes over time. Further, longitudinal studies in children to adulthood have shown that these treatments do not improve asthma severity or fixed airflow obstruction over time. In asthma, fixed airflow obstruction is caused by remodeling of the airway wall, but such airway remodeling also significantly contributes to airway closure during bronchoconstriction in acute asthmatic episodes. The goal of the current review is to understand what is known about the heterogeneity of airway remodeling in asthma and how this contributes to the disease process. We provide an overview of the existing knowledge on airway remodeling features observed in asthma, including loss of epithelial integrity, mucous cell metaplasia, extracellular matrix remodeling in both the airways and vessels, angiogenesis, and increased smooth muscle mass. While such studies have provided extensive knowledge on different aspects of airway remodeling, they have relied on biopsy sampling or pathological assessment of lungs from fatal asthma patients, which have limitations for understanding airway heterogeneity and the entire asthma syndrome. To further understand the heterogeneity of airway remodeling in asthma, we highlight the potential of in vivo imaging tools such as computed tomography and magnetic resonance imaging. Such volumetric imaging tools provide the opportunity to assess the heterogeneity of airway remodeling within the whole lung and have led to the novel identification of heterogenous gas trapping and mucus plugging as important predictors of patient outcomes. Lastly, we summarize the current knowledge of modification of airway remodeling with available asthma therapeutics to highlight the need for future studies that use in vivo imaging tools to assess airway remodeling outcomes.

The significant clinical correlation of the intratumor oral microbiome in oral squamous cell carcinoma based on tissue-derived sequencing

Abstract: Background: The microbiota is a critical component of the complex human microenvironment, impacting various physiological processes and disease development via the microbe–host interaction. In particular, the oral microbiota profoundly affects tumor development and progression. There is increasing evidence that oral microbiota is associated with the development of oral cancer, especially oral squamous cell carcinoma (OSCC). Methods: We comprehensively analyzed the oral microbiota in 133 OSCC samples worldwide. Subsequently, we evaluated the microbial compositions between OSCC patients and healthy people and their correlation with clinical parameters. The value of the oral microbiota as a diagnostic and prognostic biomarker was also determined. Results: This study found differences in critical oral microbiota between OSCC and normal controls. The most notable differences are present in p_Firmicutes, p_Actinobacteria, c_Fusobacteriia, o_Fusobacteriales, f_Fusobacteriaceae, and g_Fusobacterium. All six-level oral microorganisms were also associated with the clinical characteristics of OSCC, particularly with the clinical outcomes (survival time and status). We developed a predictive model based on this. We found that five different oral microorganisms have high confidence and can be used for clinical diagnosis and prognostic prediction, except for p_Actinobacteria. Conclusion: This study revealed that the intratumor oral microbiota of OSCC patients worldwide and the microbial signatures of OSCC patients possess similar properties in different regions, further refining the shortcomings of the current research field. We revealed that the oral microbiota could be used as a biomarker to reflect human health and disease progression status. This will provide new directions for tumor microbiome research. This means we can develop strategies through diet, probiotics, and antibiotics for cancer prevention and treatment.

Hemotoxic effects of polyethylene microplastics on mice

Abstract: Micro- or nanoplastics, which are fragmented or otherwise tiny plastic materials, have long been a source of environmental worry. Microplastics (MPs) have been well documented to alter the physiology and behavior of marine invertebrates. The effects of some of these factors are also seen in larger marine vertebrates, such as fish. More recently, mouse models have been used to investigate the potential impacts of micro- and nanoplastics on host cellular and metabolic damages as well as mammalian gut flora. The impact on erythrocytes, which carry oxygen to all cells, has not yet been determined. Therefore, the current study aims to ascertain the impact of exposure to various MP exposure levels on hematological alterations and biochemical indicators of liver and kidney functions. In this study, a C57BL/6 murine model was concentration-dependently exposed to microplastics (6, 60, and 600 μg/day) for 15 days, followed by 15 days of recovery. The results demonstrated that exposure to 600 μg/day of MPs considerably impacted RBCs’ typical structure, resulting in numerous aberrant shapes. Furthermore, concentration-dependent reductions in hematological markers were observed. Additional biochemical testing revealed that MP exposure impacted the liver and renal functioning. Taken together, the current study reveals the severe impacts of MPs on mouse blood parameters, erythrocyte deformation, and consequently, anemic patterns of the blood.

Effects of spinetoram and glyphosate on physiological biomarkers and gut microbes in Bombus terrestris

Abstract: The sublethal effects of pesticide poisoning will have significant negative impacts on the foraging and learning of bees and bumblebees, so it has received widespread attention. However, little is known about the physiological effects of sublethal spinetoram and glyphosate exposure on bumblebees. We continuously exposed Bombus terrestris to sublethal (2.5 mg/L) spinetoram or glyphosate under controlled conditions for 10 days. The superoxide dismutase, glutathione-S-transferase, carboxylesterase, prophenoloxidase, α-amylase and protease activities, and changes in gut microbes were measured to understand the effects of sublethal pesticide exposure on the physiology and gut microbes of bumblebees. Sublethal pesticide exposure to significantly increased superoxide dismutase activity and significantly decreased gut α-amylase activity in bumblebees but had no significant effect on glutathione-S-transferase, carboxylesterase or gut protease activities. In addition, glyphosate increased the activity of prophenoloxidase. Interestingly, we observed that neither of the two pesticides had a significant effect on dominant gut bacteria, but glyphosate significantly altered the structure of the dominant gut fungal community, and reduced the relative abundance of Zygosaccharomyces associated with fat accumulation. These results suggest that sublethal spinetoram and glyphosate do not significantly affect the detoxification system of bumblebees, but may affect bumblebee health by inhibiting energy acquisition. Our results provide information on the sublethal effects of exposure to low concentrations of glyphosate and spinetoram on bumblebees in terms of physiology and gut microbes.

Role of glucocorticoid and mineralocorticoid receptors in rainbow trout (Oncorhynchus mykiss) skeletal muscle: A transcriptomic perspective of cortisol action

Abstract: Cortisol is an essential regulator of neuroendocrine stress responses in teleost. Cortisol performs its effects through the modulation of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), activating gene expression. Until now the contribution of both receptors in the global transcriptional response in teleost skeletal muscle has not been explored. To understand in a comprehensive and global manner how GR and MR modulates the skeletal muscle transcriptomic response, we performed RNA-seq analysis. Juvenile rainbow trout (Oncorhynchus mykiss) pretreated with a suppressor of endogenous cortisol production were intraperitoneally injected with cortisol (10 mg/kg). We also included a treatment with mifepristone (GR antagonist) and eplerenone (MR antagonist) in the presence or absence of cortisol. cDNA libraries were constructed from the skeletal muscle of rainbow trout groups: vehicle, cortisol, mifepristone, eplerenone, mifepristone/cortisol and eplerenone/cortisol. RNA-seq analysis revealed that 135 transcripts were differentially expressed in cortisol vs. mifepristone/cortisol group, mainly associated to inflammatory response, ion transmembrane transport, and proteolysis. In the other hand, 68 transcripts were differentially expressed in cortisol vs. eplerenone/cortisol group, mainly associated to muscle contraction, and regulation of cell cycle. To validate these observations, we performed in vitro experiments using rainbow trout myotubes. In myotubes treated with cortisol, we found increased expression of cxcr2, c3, and clca3p mediated by GR, associated with inflammatory response, proteolysis, and ion transmembrane transport, respectively. Contrastingly, MR modulated the expression of myh2 and gadd45g mainly associated with muscle contraction and regulation of cell cycle, respectively. These results suggest that GR and MR have a differential participation in the physiological response to stress in teleost skeletal muscle.

The effects of velocity-based versus percentage-based resistance training on athletic performances in sport-collegiate female basketball players

Abstract: Introduction: The study compared the effects of 6-week (2 sessions/week) velocity-based resistance training (VBRT) and percentage-based resistance training (PBRT) on athletic performance in Sport-College female basketball players. Methods: Fifteen participants were assigned to the VBRT (n = 8) or PBRT (n = 7) groups. The load in VBRT group were determined through the sessional target velocity and velocity loss monitoring, whereas PBRT group used a fixed-load based on percentage of 1-repetition maximum (1RM). Both groups completed intervention that involved the free weight back squat and bench press using the same relative load (linear periodization from 65% to 95% 1RM). Training loads data was continuously recorded. Measurements at baseline (T0) and post-training (T2) included 1RM, countermovement-jump (CMJ), squat-jump (SJ), eccentric-utilization-ratio (EUR), drop-jump height and reactive-strength-index (DJ, DJ-RSI), plyometric-push-up (PPU), 505 change-of-direction (COD), 10-m、20-m sprint (T-10、T-20), 17 × 15 m drill-lines (17-drill), Hexagon agility, and functional movement screen (FMS). A mid-term (T1) assessment was included to investigate the short-term effects of both methods and the fluctuation of personalized 1RM. Results: No between-group differences were observed at T0 for descriptive variables (p > 0.05). Both groups showed significant improvement in strength gains for back squat and bench press, but VBRT showed likely to very likely favorable improvements in CMJ, SJ, EUR, DJ-RSI, Hexagon and COD among athletic performance. The VBRT showed likely to very likely improvements in 17-drill and DJ, while PBRT showed unclear effects. The lifted weights adjusted by VBRT method were higher than prescribed by PBRT (p < 0.05) for the same subjects. Conclusion: Compared with fixed-load PBRT, VBRT enhanced power and athletic performance despite similar strength gains. VBRT can be regarded as a more functional resistance-training method under linear periodization.

Virulence of entomopathogenic fungi against fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae) under laboratory conditions

Abstract: Maize is an essential crop of China. The recent invasion of Spodoptera frugiperda, also known as fall armyworm (FAW), poses a danger to the country’s ability to maintain a sustainable level of productivity from this core crop. Entomopathogenic fungi (EPF) Metarhizium anisopliae MA, Penicillium citrinum CTD-28 and CTD-2, Cladosporium sp. BM-8, Aspergillus sp. SE-25 and SE-5, Metarhizium sp. CA-7, and Syncephalastrum racemosum SR-23 were tested to determine their effectiveness in causing mortality in second instars, eggs, and neonate larvae. Metarhizium anisopliae MA, P. citrinum CTD-28, and Cladosporium sp. BM-8 caused the highest levels of egg mortality, with 86.0, 75.3, and 70.0%, respectively, followed by Penicillium sp. CTD-2 (60.0%). Additionally, M. anisopliae MA caused the highest neonatal mortality of 57.1%, followed by P. citrinum CTD-28 (40.7%). In addition, M. anisopliae MA, P. citrinum CTD-28, and Penicillium sp. CTD-2 decreased the feeding efficacy of second instar larvae of FAW by 77.8, 75.0, and 68.1%, respectively, followed by Cladosporium sp. BM-8 (59.7%). It is possible that EPF will play an important role as microbial agents against FAW after further research is conducted on the effectiveness of these EPF in the field.

Machine learning and reduced order modelling for the simulation of braided stent deployment

Abstract: Endoluminal reconstruction using flow diverters represents a novel paradigm for the minimally invasive treatment of intracranial aneurysms. The configuration assumed by these very dense braided stents once deployed within the parent vessel is not easily predictable and medical volumetric images alone may be insufficient to plan the treatment satisfactorily. Therefore, here we propose a fast and accurate machine learning and reduced order modelling framework, based on finite element simulations, to assist practitioners in the planning and interventional stages. It consists of a first classification step to determine a priori whether a simulation will be successful (good conformity between stent and vessel) or not from a clinical perspective, followed by a regression step that provides an approximated solution of the deployed stent configuration. The latter is achieved using a non-intrusive reduced order modelling scheme that combines the proper orthogonal decomposition algorithm and Gaussian process regression. The workflow was validated on an idealized intracranial artery with a saccular aneurysm and the effect of six geometrical and surgical parameters on the outcome of stent deployment was studied. We trained six machine learning models on a dataset of varying size and obtained classifiers with up to 95% accuracy in predicting the deployment outcome. The support vector machine model outperformed the others when considering a small dataset of 50 training cases, with an accuracy of 93% and a specificity of 97%. On the other hand, real-time predictions of the stent deployed configuration were achieved with an average validation error between predicted and high-fidelity results never greater than the spatial resolution of 3D rotational angiography, the imaging technique with the best spatial resolution (0.15 mm). Such accurate predictions can be reached even with a small database of 47 simulations: by increasing the training simulations to 147, the average prediction error is reduced to 0.07 mm. These results are promising as they demonstrate the ability of these techniques to achieve simulations within a few milliseconds while retaining the mechanical realism and predictability of the stent deployed configuration.

Athlete level, sport-type, and gender influences on training, mental health, and sleep during the early COVID-19 lockdown in Malaysia

Abstract: Purpose: We evaluated the extent of changes in training practices, recovery, mental health, and sleep patterns of athletes during the early COVID-19 lockdown in a single country-cohort. Methods: A total of 686 athletes (59% male, 41% female; 9% World Class, 28% International, 29% National, 26% State, 8% Recreational) from 50 sports (45% individual, 55% team) in Malaysia completed an online, survey-based questionnaire study. The questions were related to training practices (including recovery and injury), mental health, and sleep patterns. Results: Relative to pre-lockdown, training intensity (−34%), frequency (−20%, except World-Class), and duration (−24%–59%, especially International/World-Class) were compromised, by the mandated lockdown. During the lockdown, more space/access (69%) and equipment (69%) were available for cardiorespiratory training, than technical and strength; and these resources favoured World-Class athletes. Most athletes trained for general strength/health (88%) and muscular endurance (71%); and some used innovative/digital training tools (World-Class 48% vs. lower classification-levels ≤34%). More World-Class, International, and National athletes performed strength training, plyometrics, and sport-specific technical skills with proper equipment, than State/Recreational athletes. More females (42%) sourced training materials from social media than males (29%). Some athletes (38%) performed injury prevention exercises; 18% had mild injuries (knees 29%, ankles 26%), and 18% received a medical diagnosis (International 31%). Lower-level athletes (e.g., State 44%) disclosed that they were mentally more vulnerable; and felt more anxious (36% vs. higher-levels 14%–21%). Sleep quality and quantity were “normal” (49% for both), “improved” (35% and 27%), and only 16% and 14% (respectively) stated “worsened” sleep. Conclusion: Lockdown compromised training-related practices, especially in lower-level athletes. Athletes are in need of assistance with training, and tools to cope with anxiety that should be tailored to individual country requirements during lockdown situations. In particular, goal-driven (even if it is at home) fitness training, psychological, financial, and lifestyle support can be provided to reduce the difficulties associated with lockdowns. Policies and guidelines that facilitate athletes (of all levels) to train regularly during the lockdown should be developed.

Association of cyclophilins and cardiovascular risk factors in coronary artery disease

Abstract: Cyclophilins are chaperone proteins that play important roles in signal transduction. Among them, cyclophilins A, B, C, and D were widely associated with inflammation and cardiovascular diseases. Cyclophilins A and C have been proposed as coronary artery disease biomarkers. However, less is known about their relationship with cardiovascular risk factors. Therefore, this study aimed to determine the association between cyclophilin A, B, C, and D and cardiovascular risk factors in coronary artery disease. Serum levels of cyclophilins were measured in 167 subjects (subdivided according to cardiovascular risk factors presence). This study reveals that cyclophilin A and C are elevated in patients regardless of the risk factors presence. Moreover, cyclophilin B is elevated in male patients with hypertension, type 2 diabetes, or high glucose levels. In addition, cyclophilins A, B, and C were significantly correlated with cardiovascular risk factors, but only cyclophilin B was associated with type 2 diabetes. The multivariate analysis strengthens the predictive value for coronary artery disease presence of cyclophilin A (>8.2 ng/mL) and cyclophilin C (>17.5 pg/mL) along with the cardiovascular risk factors tobacco, hypertension, dyslipidemia, and high glucose and cholesterol levels. Moreover, the risk of coronary artery disease is increased in presence of cyclophilin B levels above 63.26 pg/mL and with hypertension or dyslipidemia in male patients. Consequently, cyclophilins A and C serum levels are reinforced as useful coronary artery disease biomarkers, meanwhile, cyclophilin B is a valuable biomarker in the male population when patients are also suffering from hypertension or dyslipidemia.

Warm-up stretching exercises and physical performance of youth soccer players

Abstract: This study aims to compare the effects of standard warm-up versus warm-up using stretching exercises on the physical performance of male youth soccer players. Eighty-five male soccer players (age: 10.3 ± 4.3 years; body mass index: 19.8 ± 4.3 kg/m2) were assessed for countermovement jump height (CMJ, cm), 10 m, 20 m and 30 m running sprint speed (s) and ball kicking speed (km/h) for the dominant and non-dominant leg under five (randomized) warm-up conditions. Using 72 h of recovery between conditions, the participants completed a control condition (CC) and four experimental conditions, including static stretching (SSC), dynamic stretching (DSC), ballistic stretching (BSC), and proprioceptive neuromuscular facilitation (PNFC) exercises. All warm-up conditions had a duration of 10 minutes. The main results indicate that no significant differences (p > 0.05) were found between warm-up conditions compared to CC in CMJ (CC = 28.1 ± 4.9; SSC = 28.4 ± 4.9; DSC = 30.9 ± 4.8; BSC = 30.9 ± 5.2; PNFC = 28.4 ± 5.0), 10 m sprint (CC = 2.42 ± 0.4; SSC = 2.50 ± 0.4; DSC = 2.30 ± 0.3; BSC = 2.27 ± 0.3; PNFC = 2.53 ± 0.4), 20 m sprint (CC = 5.42 ± 0.9; SSC = 5.59 ± 0.9; DSC = 5.37 ± 0.9; BSC = 5.40 ± 0.9; PNFC = 5.44 ± 0.9), 30 m sprint (CC = 8.05 ± 1.3; SSC = 8.27 ± 1.3; DSC = 8.01 ± 1.3; BSC = 8.00 ± 1.3; PNFC = 8.12 ± 1.3), ball kicking speed for dominant (CC = 56.2 ± 4.9; SSC = 55.3 ± 5.2; DSC = 56.9 ± 5.8; BSC = 57.3 ± 5.8; PNFC = 55.7 ± 5.2) and non-dominant leg (CC = 52.8 ± 3.4; SSC = 51.8 ± 4.6; DSC = 53.5 ± 5.4; BSC = 53.6 ± 4.9; PNFC = 52.5 ± 4.0). In conclusion, compared to standard warm-up, stretching-based warm-up exerts no effect on male youth soccer players jump height, sprint speed and ball kicking speed.

Human umbilical cord mesenchymal stem cells derived extracellular vesicles alleviate salpingitis by promoting M1–to–M2 transformation

Abstract: Background: With an increasing number of patients experiencing infertility due to chronic salpingitis after Chlamydia trachomatis (CT) infection, there is an unmet need for tissue repair or regeneration therapies. Treatment with human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EV) provides an attractive cell-free therapeutic approach. Methods: In this study, we investigated the alleviating effect of hucMSC-EV on tubal inflammatory infertility caused by CT using in vivo animal experiments. Furthermore, we examined the effect of hucMSC-EV on inducing macrophage polarization to explore the molecular mechanism. Results: Our results showed that tubal inflammatory infertility caused by Chlamydia infection was significantly alleviated in the hucMSC-EV treatment group compared with the control group. Further mechanistic experiments showed that the application of hucMSC-EV induced macrophage polarization from the M1 to the M2 type via the NF-κB signaling pathway, improved the local inflammatory microenvironment of fallopian tubes and inhibited tube inflammation. Conclusion: We conclude that this approach represents a promising cell-free avenue to ameliorate infertility due to chronic salpingitis. Graphical Abstract

Effects of a paddling-based high-intensity interval training prescribed using anaerobic speed reserve on sprint kayak performance

Abstract: The aim of this study was to investigate physiological and performance adaptations to high-intensity interval training (HIIT) prescribed as a proportion of anaerobic speed reserve (ASR) compared to HIIT prescribed using maximal aerobic speed (MAS). Twenty-four highly trained sprint kayak athletes were randomly allocated to one of three 4-weak conditions (N = 8) (ASR-HIIT) two sets of 6 × 60 s intervals at ∆%20ASR (MAS-HIIT) six 2 min paddling intervals at 100% maximal aerobic speed (MAS); or controls (CON) who performed six sessions/week of 1-h traditional endurance paddling at 70%–80% maximum HR. A graded exercise test was performed on a kayak ergometer to determine peak oxygen uptake (V̇O2peak), MAS, V̇O2/HR, and ventilatory threshold. Also, participants completed four consecutive upper-body wingate tests to asses peak and average power output. Significant increases in V̇O2peak (ASR-HIIT = 6.9%, MAS-HIIT = 4.8%), MAS (ASR-HIIT = 7.2%, MAS-HIIT = 4.8%), ASR (ASR-HIIT = −25.1%, MAS-HIIT = −15.9%), upper-body Wingate peak power output and average power output (p < 0.05 for both HIIT groups) were seen compared with pre-training. Also, ASR-HIIT resulted in a significant decrease in 500-m − 1.9 % , and 1,000 − m − 1.5 % paddling time. Lower coefficient of variation values were observed for the percent changes of the aforementioned factors in response to ASR-HIIT compared to MAS-HIIT. Overall, a short period of ASR-HIIT improves 500-m and 1,000-m paddling performances in highly trained sprint kayak athletes. Importantly, inter-subject variability (CV) of physiological adaptations to ASR-HIIT was lower than MAS-HIIT. Individualized prescription of HIIT using ASR ensures similar physiological demands across individuals and potentially facilitates similar degrees of physiological adaptation.

Effect of the 3q26-coding oncogene SEC62 as a potential prognostic marker in patients with ovarian neoplasia

Abstract: With approximately 220,000 newly diagnosed cases per year, ovarian cancer is among the most frequently occurring cancers among women and the second leading cause of death from gynecological malignancies worldwide. About 70% of these cancers are diagnosed in advanced stages (FIGO IIB–IV), with a 5-year survival rate of 20–30%. Due to the poor prognosis of this disease, research has focused on its pathogenesis and the identification of prognostic factors. One possible approach for the identification of biological markers is the identification of tumor entity-specific genetic “driver mutations”. One such mutation is 3q26 amplification in the tumor driver SEC62, which has been identified as relevant to the pathogenesis of ovarian cancer. This study was conducted to investigate the role of SEC62 in ovarian malignancies. Patients with ovarian neoplasias (borderline tumors of the ovary and ovarian cancer) who were treated between January 2007 and April 2019 at the Department of Gynecology and Obstetrics, Saarland University Hospital, were included in this retrospective study. SEC62 expression in tumor tissue samples taken during clinical treatment was assessed immunohistochemically, with the calculation of immunoreactivity scores according to Remmele and Stegner, Pathologe, 1987, 8, 138–140. Correlations of SEC62 expression with the TNM stage, histological subtype, tumor entity, and oncological outcomes (progression-free and overall survival) were examined. The sample comprised 167 patients (123 with ovarian cancer and 44 with borderline tumors of the ovary) with a median age of 60 (range, 15–87) years. At the time of diagnosis, 77 (46%) cases were FIGO stage III. All tissue slides showed SEC62 overexpression in tumor cells and no SEC62 expression in other cells. Median immunoreactivity scores were 8 (range, 2–12) for ovarian cancer and 9 (range, 4–12) for borderline tumors of the ovary. Patients with borderline tumors of the ovary as well as patients with ovarian cancer and an immunoreactive score (IRS) ≤ 9 showed an improved overall survival compared to those presenting with an IRS score >9 (p = 0.03). SEC62 seems to be a prognostic biomarker for the overall survival of patients with ovarian malignancies.

CellPalmSeq: A curated RNAseq database of palmitoylating and de-palmitoylating enzyme expression in human cell types and laboratory cell lines

Abstract: The reversible lipid modification protein S-palmitoylation can dynamically modify the localization, diffusion, function, conformation and physical interactions of substrate proteins. Dysregulated S-palmitoylation is associated with a multitude of human diseases including brain and metabolic disorders, viral infection and cancer. However, the diverse expression patterns of the genes that regulate palmitoylation in the broad range of human cell types are currently unexplored, and their expression in commonly used cell lines that are the workhorse of basic and preclinical research are often overlooked when studying palmitoylation dependent processes. We therefore created CellPalmSeq (https://cellpalmseq.med.ubc.ca), a curated RNAseq database and interactive webtool for visualization of the expression patterns of the genes that regulate palmitoylation across human single cell types, bulk tissue, cancer cell lines and commonly used laboratory non-human cell lines. This resource will allow exploration of these expression patterns, revealing important insights into cellular physiology and disease, and will aid with cell line selection and the interpretation of results when studying important cellular processes that depend on protein S-palmitoylation.

Integrated metabolomics and lipidomics evaluate the alterations of flavor precursors in chicken breast muscle with white striping symptom

Abstract: White striping (WS) is the most common myopathy in the broiler chicken industry. To reveal flavor changes of WS meat objectively, flavor precursors of WS breast muscle were evaluated systematically with integrated metabolomics and lipidomics. The results showed that WS could be distinguished from normal controls by E-nose, and four volatile compounds (o-xylene, benzene, 1,3-dimethyl, 2-heptanone and 6-methyl and Acetic acid and ethyl ester) were detected as decreased compounds by gas chromatography-mass spectrometry. Lipidomic analysis showed that WS breast fillets featured increased neutral lipid (83.8%) and decreased phospholipid molecules (33.2%). Targeted metabolomic analysis indicated that 16 hydrophilic metabolites were altered. Thereinto, some water-soluble flavor precursors, such as adenosine monophosphate, GDP-fucose and L-arginine increased significantly, but fructose 1,6-bisphosphate and L-histidine significantly decreased in the WS group. These results provided a systematic evaluation of the flavor precursors profile in the WS meat of broiler chickens.

Energy metabolism disturbance in migraine: From a mitochondrial point of view

Abstract: Migraine is a serious central nervous system disease with a high incidence rate. Its pathogenesis is very complex, which brings great difficulties for clinical treatment. Recently, many studies have revealed that mitochondrial dysfunction may play a key role in migraine, which affects the hyperosmotic of Ca2+, the excessive production of free radicals, the decrease of mitochondrial membrane potential, the imbalance of mPTP opening and closing, and the decrease of oxidative phosphorylation level, which leads to neuronal energy exhaustion and apoptosis, and finally lessens the pain threshold and migraine attack. This article mainly introduces cortical spreading depression, a pathogenesis of migraine, and then damages the related function of mitochondria, which leads to migraine. Oxidative phosphorylation and the tricarboxylic acid cycle are the main ways to provide energy for the body. 95 percent of the energy needed for cell survival is provided by the mitochondrial respiratory chain. At the same time, hypoxia can lead to cell death and migraine. The pathological opening of the mitochondrial permeability transition pore can promote the interaction between pro-apoptotic protein and mitochondrial, destroy the structure of mPTP, and further lead to cell death. The increase of mPTP permeability can promote the accumulation of reactive oxygen species, which leads to a series of changes in the expression of proteins related to energy metabolism. Both Nitric oxide and Calcitonin gene-related peptide are closely related to the attack of migraine. Recent studies have shown that changes in their contents can also affect the energy metabolism of the body, so this paper reviews the above mechanisms and discusses the mechanism of brain energy metabolism of migraine, to provide new strategies for the prevention and treatment of migraine and promote the development of individualized and accurate treatment of migraine.

Predictive utility of commercial grade technologies for assessing musculoskeletal injury risk in US Marine Corps Officer candidates

Abstract: Recently, commercial grade technologies have provided black box algorithms potentially relating to musculoskeletal injury (MSKI) risk and functional movement deficits, in which may add value to a high-performance model. Thus, the purpose of this manuscript was to evaluate composite and component scores from commercial grade technologies associations to MSKI risk in Marine Officer Candidates. 689 candidates (Male candidates = 566, Female candidates = 123) performed counter movement jumps on SPARTA™ force plates and functional movements (squats, jumps, lunges) in DARI™ markerless motion capture at the start of Officer Candidates School (OCS). De-identified MSKI data was acquired from internal OCS reports for those who presented to the Physical Therapy department for MSKI treatment during the 10 weeks of training. Logistic regression analyses were conducted to validate the utility of the composite scores and supervised machine learning algorithms were deployed to create a population specific model on the normalized component variables in SPARTA™ and DARI™. Common MSKI risk factors (cMSKI) such as older age, slower run times, and females were associated with greater MSKI risk. Composite scores were significantly associated with MSKI, although the area under the curve (AUC) demonstrated poor discrimination (AUC = .55–.57). When supervised machine learning algorithms were trained on the normalized component variables and cMSKI variables, the overall training models performed well, but when the training models were tested on the testing data the models classified MSKI “by chance” (testing AUC avg = .55–.57) across all models. Composite scores and component population specific models were poor predictors of MSKI in candidates. While cMSKI, SPARTA™, and DARI™ models performed similarly, this study does not dismiss the use of commercial technologies but questions the utility of a singular screening task to predict MSKI over 10 weeks. Further investigations should evaluate occupation specific screening, serial measurements, and/or load exposure for creating MSKI risk models.

Full-length huntingtin is palmitoylated at multiple sites and post-translationally myristoylated following caspase-cleavage

Abstract: Introduction: Huntington disease is an autosomal dominant neurodegenerative disorder which is caused by a CAG repeat expansion in the HTT gene that codes for an elongated polyglutamine tract in the huntingtin (HTT) protein. Huntingtin is subjected to multiple post-translational modifications which regulate its cellular functions and degradation. We have previously identified a palmitoylation site at cysteine 214 (C214), catalyzed by the enzymes ZDHHC17 and ZDHHC13. Reduced palmitoylation level of mutant huntingtin is linked to toxicity and loss of function. Moreover, we have described N-terminal myristoylation by the N-myristoyltransferases of a short fragment of huntingtin (HTT553-586) at glycine 553 (G553) following proteolysis at aspartate 552 (D552). Results: Here, we show that huntingtin is palmitoylated at numerous cysteines: C105, C433, C3134 and C3144. In addition, we confirm that full-length huntingtin is cleaved at D552 and post-translationally myristoylated at G553. Importantly, blocking caspase cleavage at the critical and pathogenic aspartate 586 (D586) significantly increases posttranslational myristoylation of huntingtin. In turn, myristoylation of huntingtin promotes the co-interaction between C-terminal and N-terminal huntingtin fragments, which is also protective. Discussion: This suggests that the protective effect of inhibiting caspase-cleavage at D586 may be mediated through post-translational myristoylation of huntingtin at G553.