Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative Stress, Inflammation, and Activators of Mitochondrial Biogenesis: Tempol Targets in the Diaphragm Muscle of Exercise Trained-mdx Mice

The mdx mouse phenotype aggravated by chronic exercise on a treadmill makes this murine model more reliable for the study of muscular dystrophy. Thus, to better assess the Tempol effect on dystrophic pathways, the analyses in this study were performed in the blood samples and diaphragm muscle from treadmill trained adult (7–11-weeks old) mdx animals. The mdx mice were divided into three groups: mdxSed, sedentary controls (n = 28); mdxEx, exercise-trained animals (n = 28); and mdxEx+T, exercise-trained animals with the Tempol treatment (n = 28). The results demonstrated that the Tempol treatment promoted muscle strength gain, prevented muscle damage, reduced the inflammatory process, oxidative stress, and angiogenesis regulator, and up regulated the activators of mitochondrial biogenesis. The main new findings of this study are that Tempol reduced the NF-κB and increased the PGC1-α and PPARδ levels in the exercise-trained-mdx mice, which are probably related to the ability of this antioxidant to scavenge excessive ROS. These results reinforce the use of Tempol as a potential therapeutic strategy in DMD.
Breaching the Delivery Barrier: Chemical and Physical Airway Epithelium Disruption Strategies for Enhancing Lentiviral-Mediated Gene Therapy

The lungs have evolved complex physical, biological and immunological defences to prevent foreign material from entering the airway epithelial cells. These mechanisms can also affect both viral and non-viral gene transfer agents, and significantly diminish the effectiveness of airway gene-addition therapies. One strategy to overcome the physical barrier properties of the airway is to transiently disturb the integrity of the epithelium prior to delivery of the gene transfer vector. In this study, chemical (lysophosphatidylcholine, LPC) and physical epithelium disruption using wire abrasion were compared for their ability to improve airway-based lentiviral (LV) vector mediated transduction and reporter gene expression in rats. When luciferase expression was assessed at 1-week post LV delivery, LPC airway conditioning significantly enhanced gene expression levels in rat lungs, while a long-term assessment in a separate cohort of rats at 12 months revealed that LPC conditioning did not improve gene expression longevity. In rats receiving physical perturbation to the trachea prior to gene delivery, significantly higher LacZ gene expression levels were found when compared to LPC-conditioned or LV-only control rats when evaluated 1-week post gene transfer. This proof-of-principle study has shown that airway epithelial disruption strategies based on physical perturbation substantially enhanced LV-mediated airway gene transfer in the trachea.
Cholinergic and Noradrenergic Modulation of Corticothalamic Synaptic Input From Layer 6 to the Posteromedial Thalamic Nucleus in the Rat

Cholinergic and noradrenergic neuromodulation of the synaptic transmission from cortical layer 6 of the primary somatosensory cortex to neurons in the posteromedial thalamic nucleus (PoM) was studied using an in vitro slice preparation from young rats. Cholinergic agonist carbachol substantially decreased the amplitudes of consecutive excitatory postsynaptic potentials (EPSPs) evoked by a 20 Hz five pulse train. The decreased amplitude effect was counteracted by a parallel increase of synaptic frequency-dependent facilitation. We found this modulation to be mediated by muscarinic acetylcholine receptors. In the presence of carbachol the amplitudes of the postsynaptic potentials showed a higher trial-to-trial coefficient of variation (CV), which suggested a presynaptic site of action for the modulation. To substantiate this finding, we measured the failure rate of the excitatory postsynaptic currents in PoM cells evoked by “pseudominimal” stimulation of corticothalamic input. A higher failure-rate in the presence of carbachol indicated decreased probability of transmitter release at the synapse. Activation of the noradrenergic modulatory system that was mimicked by application of norepinephrine did not affect the amplitude of the first EPSP evoked in the five-pulse train, but later EPSPs were diminished. This indicated a decrease of the synaptic frequency-dependent facilitation. Treatment with noradrenergic α-2 agonist clonidine, α-1 agonist phenylephrine, or β-receptor agonist isoproterenol showed that the modulation may partly rely on α-2 adrenergic receptors. CV analysis did not suggest a presynaptic action of norepinephrine. We conclude that cholinergic and noradrenergic modulation act as different variable dynamic controls for the corticothalamic mechanism of the frequency-dependent facilitation in PoM.
Exercise-Induced Hypoxemia in Endurance Athletes: Consequences for Altitude Exposure

Exercise-induced hypoxemia (EIH) is well-described in endurance-trained athletes during both maximal and submaximal exercise intensities. Despite the drop in oxygen (O2) saturation and provided that training volumes are similar, athletes who experience EIH nevertheless produce the same endurance performance in normoxia as athletes without EIH. This lack of a difference prompted trainers to consider that the phenomenon was not relevant to performance but also suggested that a specific adaptation to exercise is present in EIH athletes. Even though the causes of EIH have been extensively studied, its consequences have not been fully characterized. With the development of endurance outdoor activities and altitude/hypoxia training, athletes often train and/or compete in this stressful environment with a decrease in the partial pressure of inspired O2 (due to the drop in barometric pressure). Thus, one can reasonably hypothesize that EIH athletes can specifically adapt to hypoxemic episodes during exercise at altitude. Although our knowledge of the interactions between EIH and acute exposure to hypoxia has improved over the last 10 years, many questions have yet to be addressed. Firstly, endurance performance during acute exposure to altitude appears to be more impaired in EIH vs. non-EIH athletes but the corresponding physiological mechanisms are not fully understood. Secondly, we lack information on the consequences of EIH during chronic exposure to altitude. Here, we (i) review research on the consequences of EIH under acute hypoxic conditions, (ii) highlight unresolved questions about EIH and chronic hypoxic exposure, and (iii) suggest perspectives for improving endurance training.
PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease

Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Myeloid derived suppressor cells (MDSC) have been shown to be expanded during TB, but their role in human TB pathogenesis is not clear. We evaluated the frequency of circulating MDSC by flow-cytometry in 19 patients with active TB, 18 with latent TB infection (LTBI), and 12 healthy donors (HD) as control. Moreover, we investigated the capacity of MDSC to modulate the mycobactericidal activity of monocytes. The association between MDSC level and TB chest X-ray severity score was analyzed. We observed that, unlike active TB, polymorphonuclear (PMN)-MDSC are not expanded in LTBI patients, and, by performing a receiver operating characteristic (ROC) curve analysis, we found that PMN-MDSC frequency supported the discrimination between active disease and LTBI. Interestingly, we observed an association between PMN-MDSC levels and the severity of TB disease evaluated by chest X-ray. Specifically, PMN-MDSC frequency was higher in those classified with a low/mild severity score compared to those classified with a high severity score. Moreover, PMN-MDSC can impact mycobacterial growth by inducing ROS production in Bacillus Calmette et Guerin (BCG)-infected monocytes. This effect was lost when tested with M. tuberculosis (MTB), In conclusion, our data indicate that the elevated frequency of PMN-MDSC in IGRA-positive individuals is associated with active TB. Our findings also pointed out a beneficial role of PMN-MDSC during human active TB, most likely associated with the limitation of inflammation-induced tissue damage.
Market Costs and Financing Options for Grassland Carbon Sequestration: Empirical and Modelling Evidence From Qinghai, China

Asia’s grasslands provide livelihoods for some of the region’s poorest people. Widespread grassland degradation reduces the resilience and returns to herding livelihoods. Reversing degradation and conserving grasslands could not only improve herders’ situation, but also make a huge contribution to mitigating climate change by sequestering carbon in soils. However, the means for reaching each of these objectives are not necessarily the same. To realize this potentially huge dual livelihood/climate change mitigation outcome from improved grassland management, it is necessary to have detailed understanding of the processes involved in securing better livelihoods and sequestering carbon. Based on household surveys on the Tibetan Plateau and modeling results, this study estimates economic and market costs of grassland carbon sequestration, and analyzes the implications of household and carbon project cash flows for the design of financing options. Five scenarios are modeled involving cultivation of grass on severely degraded grassland (all scenarios) and reduced grazing intensity on less degraded land, which requires destocking by 29, 38, 47, 56, and 65% in each scenario). Modeling results suggest that economic benefits for herders are positive at low levels of destocking, and negative at high levels of destocking, but initial investments and opportunity costs are significant barriers to adoption for households in all destocking scenarios. Existing rural finance products are not suitable for herders to finance the necessary investments. Market costs–the cost at which transactions between herders and carbon project developers are feasible–depend on the scale of project implementation but are high compared to recent carbon market prices. Large initial investments increase project developers’ financing costs and risk, so co-financing of initial investments by government would be necessary. Therefore, public policies to support grassland carbon sequestration should consider the potential roles of a range of financial instruments.
Toward more accurate developer recommendation via inference of development activities from interaction with bug repair process

Software projects usually receive a large number of submitted bug reports every day. Manually triaging the bug reports is often time‐consuming and error‐prone; thus, it is necessary to automatically assign the bug reports to the suitable developers for bug repair, with the help of bug tracking systems. Aiming to reducing the time consumption and mismatch of bug report assignments, we present a developer recommendation model for bug repair based on weighted recurrent neural network, namely, DTPM, which contains two parts: One obtains multisource semantic information of bug reports and fuses them into high‐dimensional semantic feature vectors, and the other combines a penalty matrix into a single hidden layer neural network to obtain more reasonable developer recommendations. We conduct experiments on five datasets of open bug repositories (NetBeans, OpenOffice, GCC, Mozilla, and Eclipse), and the experimental results show that DTPM can achieve better performance than state‐of‐the‐art models LDA_KL, LDA_KL, LDA_SVM, DERTOM, DREX, and DeepTriage.
Defensive behavior of the invasive alien hornet Vespa velutina nigrithorax against potential human aggressors

In areas where wasps are common, many wasp sting incidents occur. However, guidance on the correct response to wasp attacks remains lacking. In this study, behavioral response experiments were conducted with the aim of minimizing damage from group wasp attacks. The study species was Vespa velutina, which frequently causes wasp sting injuries in the southern regions of South Korea. Results demonstrated that worker wasps showed defensive behavior when a person approached within 3 m of the nest, and the attack rate was higher when the person conducted a large arm swing. When a person walked away after touching a nest, the number of workers attacking did not significantly decrease until they reached 5 m, this reduced to less than half when the person reached 10 m. Approximately 1.3 workers attacked even up to 300 m. However, when the person ran, the number of workers attacking was almost one or less after 10 m. Therefore, it is best to escape quickly to at least 10 m to reduce injury from group attacks. When wasps attacked, even if the person crouched, the attack did not decrease. Our recommended defensive behavior when wasps attack unexpectedly is that victims should turn their face in the opposite direction to the nest or the wasps, protect their face with their hands and arms, lean forward and run away rapidly to minimize injury. Wearing a wide brim hat was very effective, preventing about 75% of stings to the head, so this is also recommended.
Visualizing the Integrity of Chloroplast Envelope by Rhodamine and Nile Red Staining

Chloroplasts are essential organelles in plant cells with many important functions. Chloroplasts isolated by Percoll density gradient centrifugation are widely used in the study of chloroplasts. The intactness of isolated chloroplasts is necessary for many of the experiments. In the past, those isolated chloroplasts were either simply believed to be intact or had to be analyzed by indirect biochemical methods. Here we show a new method to check the intactness of isolated chloroplasts by staining their envelope with fluorescent dyes, Rhodamine or Nile red, and then observing them with a fluorescence microscope. With this method, broken chloroplasts and intact chloroplasts can be distinguished easily and their integrity can be checked in a few minutes. Results of this method agreed well with those of biochemical methods. Moreover, we have also found that sometimes the middle layer chloroplasts from the Percoll gradient centrifugation could be mostly broken, which could cause mistakes in the experiment. With our method, this problem can be easily found. This chloroplast envelope staining method can be used in the preparation of isolated chloroplasts to ensure the intactness.
Intrauterine Hypoxia Changed the Colonization of the Gut Microbiota in Newborn Rats

Background: Accumulating evidence suggests a connection between the gut microbiota and neonatal diseases. Hypoxia may play an important role in the intestinal lesions in neonates. Objective: This study aims to determine whether the gut microbiota differs between intrauterine hypoxic rats and healthy controls and to identify the factors that influence the changes in the gut microbiota. Methods: We constructed an intrauterine hypoxia model in rats and collected the intestinal contents of intrauterine hypoxic newborn rats and normal newborn rats within 4 h and on the seventh day after birth. They were divided them into the intrauterine hypoxia first-day group (INH1), intrauterine hypoxia seventh-day group (INH7), normal first-day group (NOR1), and normal seventh-day group (NOR7). The contents of the intestines were sequenced with 16S rRNA sequencing, the sequencing results were analyzed for biological information, and the differences in the diversity, richness, and individual taxa among the groups were analyzed. Results: The abundance of the gut microbiota of neonatal rats with intrauterine hypoxia was higher than that of the control group rats. Intrauterine hypoxia altered the structural composition of the gut microbiota in neonatal rats. The INH1 group showed increased species richness, phylogenetic diversity, and β-diversity, and altered relative abundance in several taxa compared to those in the control group. The differences in the microbiota among the four groups were significantly higher than those within the group, and the differences in the abundance and diversity of the INH7 and NOR7 groups decreased after 7 days of suckling. Functional analysis based on the Cluster of Orthologous Groups (COG) suggested that 23 functional COG categories. There was no significant difference in the functional categories between the hypoxia group and the normal group. Conclusion: Intrauterine hypoxia changed the initial colonization of the gut microbiota in neonatal rats. It could increase the species richness and β-diversity of the gut microbiota, and altered relative abundances of several taxa.
Editorial: Cardiac Hypertrophy: From Compensation to Decompensation and Pharmacological Interventions

Cardiac hypertrophy is not a single disease, but a complication and a pathological process of many forms of cardiovascular disease, such as hypertension, congestive heart failure, valvular diseases and ischemic diseases, etc. (Yu et al., 2020). It is characterized by abnormal increases in mass and volume of myocardium at the whole heart level, in the size of individual myocyte at cell level, and in synthesis of protein and reprogramming expression of fetal genes at molecule level (Dodge-Kafka et al., 2019; Zhang et al., 2020). Myocardial hypertrophy is an important aspect of myocardial remodeling, which including not only the hypertrophic growth of myocytes but also the proliferation and activation of interstitial fibroblasts to produce intercellular matrix, namely fibrosis (Ge et al., 2021). These three pathological processes, cardiomyocyte hypertrophy, fibrosis and remodeling, are overlapped and closely related to each other. Cardiac remodeling involves metabolic, mechanical, electrical, and structural alterations (Pitoulis and Terracciano, 2020). It is initially an adaptive response to pressure or volume overload. The myocardium undergoes hypertrophic growth as a compensatory measure aiming to improve myocardial contractility, reduce wall stress and maintain cardiac output. However, increase in mass and volume of myocardial tissue inevitably increase the oxygen consumption and dysfunction of energy metabolism in myocardial tissue (Nakamura and Sadoshima, 2018). Simultaneously, apoptosis, necrosis and autophagic cell death occur in cardiac myocytes, and proliferation and activation arise in fibroblasts, leading to interstitial fibrosis (Zhu and sun, 2018). The continued presence and evolving hypertrophy eventually lead to decompensation of heart function (Messerli et al., 2017; Oldfield et al., 2020). Many studies have demonstrated that ventricular hypertrophy and remodeling is associated with a significantly increased risk of heart failure, malignant arrhythmia, and even sudden death, and is thought to be an independent risk factor for increasing morbidity and mortality of cardiovascular diseases (He et al., 2020). Therefore, clinical guidelines in many countries and organizations have suggested it as primary goal to control or reverse cardiac hypertrophy in the therapeutics of hypertension and chronic heart failure (Di Palo and Barone, 2020). Multiple signal transduction pathways involving Gq-phospholipase C-diacylglycerol (DAG)/ inositol triphosphate (IP3), mitogen-activated protein kinases, calcineurin-nuclear factor of activated T cells (NFAT), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), mammalian target of Edited and reviewed by: Francesco Rossi, University of Campania Luigi Vanvitelli, Italy
Indigenous Knowledge and Forest Succession Management in the Brazilian Amazon: Contributions to Reforestation of Degraded Areas

The indigenous systems of agricultural and forest management in the Amazon are characterized by a deep knowledge of ecological processes, biodiversity, and the use and management of fire. The influence of these systems on the distribution of biodiversity includes semi-domesticated and domesticated species and landscapes, which have led to extensive anthropogenic or cultural forests. However, in many places, the livelihoods of indigenous peoples are being transformed by the intensification of agriculture and social, ecological, and economic changes, putting at risk the sustainability of production systems and food security and sovereignty of these peoples. In the last years, in the Xingu Indigenous Territory (XIT), the food production systems and the form of occupation of territories have changed, affecting the recovery of secondary forests, which now demand a too long period. The increase in the number and frequency of fires has aggravated this situation, due to a drier climate that has become predominant in the region. Changes in climate are attributed to deforestation in the neighboring municipalities, especially in the headwaters of the Xingu river basin. This study was conducted among the Kawaiwete (Tupi-Guarani) and the Ikpeng (Carib-Arara) peoples in the XIT, in the state of Mato Grosso, Brazil. The main objective was to develop alternative techniques of forest management based on indigenous and scientific knowledge more adapted to the new livelihood contexts, aiming to favor forest regeneration in areas dominated by shifting cultivation. We sought to answer the following questions: (I) How do forests regenerate during the fallow period? (II) How can local management improve forest regeneration? (III) Are there indicator species for secondary succession, soil recovery, and vulnerability to fires? (IV) Is the increase in the number of fires affecting the sustainability of the shifting cultivation systems? Our results show that some local practices based on indigenous knowledge have the potential to facilitate natural regeneration, such as choosing forest areas that have been recovered for agricultural use, limiting the number of cultivation cycles, protecting and selecting of individual trees during cultivation period, and attracting seed dispersers. Assisted natural regeneration strategies grounded on indigenous knowledge are promising ways to restore degraded lands of the XIT.
Is COVID-19 Keeping us Up at Night? Stress, Anxiety, and Sleep Among Adult Twins

In response to the COVID-19 pandemic, a variety of social distancing measures to mitigate the virus outbreak have been implemented. These measures may have unintended consequences on individuals’ well-being, such as increased stress, anxiety, and sleep disruptions. We investigated the extent to which individuals’ mental health status is associated with perceived changes in sleep amount and sleep quality among a sample of adult twin pairs (N = 909 pairs; 77% MZ, 23% DZ), less than a month after the outbreak was declared a pandemic by the World Health Organization. About half of participants reported no change in sleep amount (50.1%) or sleep quality (55.6%). Approximately one-third of the participants had increased amount of sleep (29.8%), and 32.9% reported a decrease in sleep quality. We found that stress and anxiety levels were associated with sleep reduction (ORs = 2.36 and 3.12 for stress and anxiety, respectively) and poorer sleep quality (ORs = 2.45 and 3.73 for stress and anxiety, respectively), even after taking into account between-family confounds. A much smaller association was observed between levels of stress and anxiety and increased sleep amount (ORs = 1.42 and 1.60 for stress and anxiety, respectively) and sleep quality (OR = 1.21 and 1.29 for stress and anxiety, respectively), which was no longer significant after controlling for between-family confounds. Our results demonstrate that stress and anxiety associated with the COVID-19 pandemic and social distancing measures may be linked to reduced sleep amount and quality.