Miracle-dz/UniFAR-FTUs huggingface dataset:
Case Report: Identification of the First Synonymous Variant of Myosin Binding Protein C3 (c.24A>C, p.P8P) Altering RNA Splicing in a Cardiomyopathy and Sudden Cardiac Death Case

Background Sudden cardiac death (SCD), based on sudden cardiac ejection cessation, is an unexpected death. Primary cardiomyopathies, including dilated cardiomyopathy (DCM), are one of main causes of SCD. The DCM is characterized by a cardiac dilatation and a reduced systolic function with a prevalence of 1/250 in adults. The DCM has been reported with more than 60 disease-causing genes, and MYBPC3 variants are one of the most common and well-known causes of DCM. Methods We identified a 29-year-old female who died of SCD. We performed a whole-exome sequencing (WES) to detect her genetic etiology and used minigene modeling and immunohistochemistry staining to verify the pathogenicity. Results We determined that the woman died of SCD caused by DCM due to an identified novel synonymous variant of MYBPC3 (NM_000256.3: c.24A>C, p.P8P) in the deceased. The variant can result in abnormal splicing, which was confirmed by minigene models and immunohistochemistry staining. Conclusion We may have identified the first deleterious synonymous variant of MYBPC3 in an SCD case and verified its significant impact on RNA splicing. Our description enriched the spectrum of MYBPC3 variants and emphasized the significance of synonymous variants that are always disregarded in genetic screening.
Genetic Diversity and Population Genetic Structure of Setosphaeria turcica From Sorghum in Three Provinces of China Using Single Nucleotide Polymorphism Markers

Setosphaeria turcica is a heterothallic fungus that is the causal agent of northern leaf blight (NLB), which is a devastating foliar disease of sorghum and maize. Despite of its adversary to crop production, little is known about the genetic diversity and population genetic structure of this pathogen from sorghum. In this study, we explored the utilization of single nucleotide polymorphism (SNP) molecular markers and three mating type-specific primers to analyze the genetic diversity, population genetic structure, and mating type distribution of 87 S. turcica isolates that had been collected in sorghum production areas from three provinces, including Henan, Shaanxi, and Shanxi in China. The populations are featured with moderate genetic diversity and relatively equal mating type distribution of MAT1-1 and MAT1-2. The genetic differentiation was significant (p < 0.05) among different populations except those from Henan and Shanxi provinces that showed particularly frequent gene flow between them. Neither the maxinum likelihood phylogenetic tree, nor principal coordinate analysis, nor genetic structure analysis was able to completely separate the three populations. The relatively low genetic distance and high genetic identification were also observed among the three populations. Nevertheless, the genetic variation within populations was the major source of variation as revealed by AMOVA analysis. The findings of this study have improved our current understanding about the genetic diversity, population genetic structure, and the distribution of mating type of S. turcica, which are useful for unraveling the epidemiology of NLB and developing effective disease management strategies.
Effects of Lower Limb Cycling Training on Different Components of Force and Fatigue in Individuals With Parkinson’s Disease

The strength of lower extremity is important for individuals to maintain balance and ambulation functions. The previous studies showed that individuals with Parkinson’s disease suffered from fatigue and strength loss of central origin. The purpose of this study was to investigate the effect of lower extremities’ cycling training on different components of force and fatigue in individuals with Parkinson’s disease. Twenty-four individuals (13 males, 11 females, mean age: 60.58 ± 8.21 years) diagnosed with idiopathic Parkinson’s disease were randomized into training and control groups. The maximum voluntary contraction (MVC) force, voluntary activation level (VA), and twitch force of knee extensors were measured using a custom-made system with surface electrical stimulation. The general, central, and peripheral fatigue indexes (GFI, CFI, and PFI) were calculated after a fatiguing cycling protocol. Subjects received 8 weeks of low resistance cycling training (training group) or self-stretching (control group) programs. Results showed that MVC, VA, and twitch force improved (p < 0.05) only in the training group. Compared to the baseline, central fatigue significantly improved in the training group, whereas peripheral fatigue showed no significant difference in two groups. The cycling training was beneficial for individuals with Parkinson’s disease not only in muscle strengthening but also in central fatigue alleviation. Further in-depth investigation is required to confirm the effect of training and its mechanism on central fatigue.
Biocontainment of Genetically Engineered Algae

Algae (including eukaryotic microalgae and cyanobacteria) have been genetically engineered to convert light and carbon dioxide to many industrially and commercially relevant chemicals including biofuels, materials, and nutritional products. At industrial scale, genetically engineered algae may be cultivated outdoors in open ponds or in closed photobioreactors. In either case, industry would need to address a potential risk of the release of the engineered algae into the natural environment, resulting in potential negative impacts to the environment. Genetic biocontainment strategies are therefore under development to reduce the probability that these engineered bacteria can survive outside of the laboratory or industrial setting. These include active strategies that aim to kill the escaped cells by expression of toxic proteins, and passive strategies that use knockouts of native genes to reduce fitness outside of the controlled environment of labs and industrial cultivation systems. Several biocontainment strategies have demonstrated escape frequencies below detection limits. However, they have typically done so in carefully controlled experiments which may fail to capture mechanisms of escape that may arise in the more complex natural environment. The selection of biocontainment strategies that can effectively kill cells outside the lab, while maintaining maximum productivity inside the lab and without the need for relatively expensive chemicals will benefit from further attention.
Hygrothermal Aging History of Amine-Epoxy Resins: Effects on Thermo-Mechanical Properties

Epoxy systems are widely used as matrix resins for fiber reinforced polymers (FRP) and, therefore, often have to withstand harsh environmental conditions. Especially in marine and offshore environments, moisture or direct water contact leads to water absorption into the epoxy resin. As a result, the mechanical properties change during application. Since diffusion at room or colder temperatures is slow, industry and academia typically use accelerated aging methods at elevated temperatures for durability prediction. However, as the water-polymer interaction is a complex combination of plasticization, physical aging, and molecular interaction, all of these mechanisms are expected to be affected by the ambient temperature. To reveal the impact of aging time and temperature on the thermo-mechanical properties of an amine-epoxy system, this publication includes various hygrothermal aging conditions, like water bath and relative humidity aging at temperatures ranging from 8°C to 70°C and relative humidity from 20% to 90%. Thus, it is demonstrated via long-term aging, DMTA and FTIR investigations that, e.g., strength, stiffness, strain to failure, and the glass transition temperature (T g ) can differ significantly depending on aging time and temperature. For example, it can be shown that water absorption at cold temperatures leads to the strongest and longest-lasting reduction in strength, although the maximum water absorption amount is lower than at higher temperatures. For the application, this means that strength differences of up to 26% can be obtained, depending on the aging method selected. Furthermore, it can be shown that conventional prediction models, such as Eyring correlation, which consider the mobility of the molecular structure for the prediction of thermo-mechanical properties, can only be used to a limited extent for prediction in hygrothermal aging. The reasons for this are seen to be, in particular, the different characteristics of the water-polymer interactions depending on the aging temperature. While plasticization dominates in cold conditions, relaxation and strong water-molecule bonds predominate in warm conditions.
Cholinergic and Neuroimmune Signaling Interact to Impact Adult Hippocampal Neurogenesis and Alcohol Pathology Across Development

Alcohol (ethanol) use and misuse is a costly societal issue that can affect an individual across the lifespan. Alcohol use and misuse typically initiates during adolescence and generally continues into adulthood. Not only is alcohol the most widely abused drug by adolescents, but it is also one of the most widely abused drugs in the world. In fact, high rates of maternal drinking make developmental ethanol exposure the most preventable cause of neurological deficits in the Western world. Preclinical studies have determined that one of the most consistent effects of ethanol is its disruption of hippocampal neurogenesis. However, the severity, persistence, and reversibility of ethanol’s effects on hippocampal neurogenesis are dependent on developmental stage of exposure and age at assessment. Complicating the neurodevelopmental effects of ethanol is the concurrent development and maturation of neuromodulatory systems which regulate neurogenesis, particularly the cholinergic system. Cholinergic signaling in the hippocampus directly regulates hippocampal neurogenesis through muscarinic and nicotinic receptor actions and indirectly regulates neurogenesis by providing anti-inflammatory regulatory control over the hippocampal environmental milieu. Therefore, this review aims to evaluate how shifting maturational patterns of the cholinergic system and its regulation of neuroimmune signaling impact ethanol’s effects on adult neurogenesis. For example, perinatal ethanol exposure decreases basal forebrain cholinergic neuron populations, resulting in long-term developmental disruptions to the hippocampus that persist into adulthood. Exaggerated neuroimmune responses and disruptions in adult hippocampal neurogenesis are evident after environmental, developmental, and pharmacological challenges, suggesting that perinatal ethanol exposure induces neurogenic deficits in adulthood that can be unmasked under conditions that strain neural and immune function. Similarly, adolescent ethanol exposure persistently decreases basal forebrain cholinergic neuron populations, increases hippocampal neuroimmune gene expression, and decreases hippocampal neurogenesis in adulthood. The effects of neither perinatal nor adolescent ethanol are mitigated by abstinence whereas adult ethanol exposure-induced reductions in hippocampal neurogenesis are restored following abstinence, suggesting that ethanol-induced alterations in neurogenesis and reversibility are dependent upon the developmental period. Thus, the focus of this review is an examination of how ethanol exposure across critical developmental periods disrupts maturation of cholinergic and neuroinflammatory systems to differentially affect hippocampal neurogenesis in adulthood.
Targeting the Ubiquitin-Proteasome System in Limb-Girdle Muscular Dystrophy With CAPN3 Mutations

LGMDR1 is caused by mutations in the CAPN3 gene that encodes calpain 3 (CAPN3), a non-lysosomal cysteine protease necessary for proper muscle function. Our previous findings show that CAPN3 deficiency leads to reduced SERCA levels through increased protein degradation. This work investigates the potential contribution of the ubiquitin-proteasome pathway to increased SERCA degradation in LGMDR1. Consistent with our previous results, we observed that CAPN3-deficient human myotubes exhibit reduced SERCA protein levels and high cytosolic calcium concentration. Treatment with the proteasome inhibitor bortezomib (Velcade) increased SERCA2 protein levels and normalized intracellular calcium levels in CAPN3-deficient myotubes. Moreover, bortezomib was able to recover mutated CAPN3 protein in a patient carrying R289W and R546L missense mutations. We found that CAPN3 knockout mice (C3KO) presented SERCA deficits in skeletal muscle in the early stages of the disease, prior to the manifestation of muscle deficits. However, treatment with bortezomib (0.8 mg/kg every 72 h) for 3 weeks did not rescue SERCA levels. No change in muscle proteasome activity was observed in bortezomib-treated animals, suggesting that higher bortezomib doses are needed to rescue SERCA levels in this model. Overall, our results lay the foundation for exploring inhibition of the ubiquitin-proteasome as a new therapeutic target to treat LGMDR1 patients. Moreover, patients carrying missense mutations in CAPN3 and presumably other genes may benefit from proteasome inhibition by rescuing mutant protein levels. Further studies in suitable models will be necessary to demonstrate the therapeutic efficacy of proteasome inhibition for different missense mutations.
Identification and Characterization of Bacillus tequilensis GYUN-300: An Antagonistic Bacterium Against Red Pepper Anthracnose Caused by Colletotrichum acutatum in Korea

Anthracnose is a fungal disease caused by Colletotrichum species and has detrimental effects on many crops, including red pepper. This study used Bacillus tequilensis GYUN-300 (GYUN-300), which exhibit antagonistic activity against the fungal pathogen, Colletotrichum acutatum. This pathogen causes anthracnose that manifests primarily as a fruit rot in red pepper. There have been little efforts to identify antagonistic bacteria from mushrooms; this strain of bacteria was identified as B. tequilensis using BIOLOG and 16S rDNA sequencing analysis. The genetic mechanism underpinning the biocontrol traits of GYUN-300 was characterized using the complete genome sequence of GYUN-300, which was closely compared to related strains. GYUN-300 inhibited mycelial growth and spore germination of C. acutatum under in vitro conditions. Important antagonistic traits, such as siderophore production, solubilization of insoluble phosphate, and production of lytic enzymes (cellulase, protease, and amylase), were observed in GYUN-300, These trains promoted growth in terms of seed germination and vigorous seedling growth compared to the non-treated control. When red pepper fruits were treated with GYUN-300, the preventive and curative effects were 66.6 and 38.3% effective, respectively, in wounded red pepper fruits; there was no difference between the preventive and curative effects in non-wounded red pepper fruits. Furthermore, GYUN-300 was resistant to several commercial fungicides, indicating that GYUN-300 bacterial cells may also be used synergistically with chemical fungicides to increase biocontrol efficiency. Based on in vitro results, GYUN-300 played a role to control anthracnose disease effectively in field conditions when compared to other treatments and non-treated controls. The results from this study provide a better understanding of the GYUN-300 strain as an effective biocontrol agent against red pepper anthracnose; this form of biocontrol provides an environment-friendly alternative to chemical fungicides.
Oral and Gut Microbial Dysbiosis and Non-alcoholic Fatty Liver Disease: The Central Role of Porphyromonas gingivalis

Gut microbiota play many important roles, such as the regulation of immunity and barrier function in the intestine, and are crucial for maintaining homeostasis in living organisms. The disruption in microbiota is called dysbiosis, which has been associated with various chronic inflammatory conditions, food allergies, colorectal cancer, etc. The gut microbiota is also affected by several other factors such as diet, antibiotics and other medications, or bacterial and viral infections. Moreover, there are some reports on the oral-gut-liver axis indicating that the disruption of oral microbiota affects the intestinal biota. Non-alcoholic fatty liver disease (NAFLD) is one of the systemic diseases caused due to the dysregulation of the oral-gut-liver axis. NAFLD is the most common liver disease reported in the developed countries. It includes liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. Recently, accumulating evidence supports an association between NAFLD and dysbiosis of oral and gut microbiota. Periodontopathic bacteria, especially Porphyromonas gingivalis, have been correlated with the pathogenesis and development of NAFLD based on the clinical and basic research, and immunology. P. gingivalis was detected in the liver, and lipopolysaccharide from this bacteria has been shown to be involved in the progression of NAFLD, thereby indicating a direct role of P. gingivalis in NAFLD. Moreover, P. gingivalis induces dysbiosis of gut microbiota, which promotes the progression of NAFLD, through disrupting both metabolic and immunologic pathways. Here, we review the roles of microbial dysbiosis in NAFLD. Focusing on P. gingivalis, we evaluate and summarize the most recent advances in our understanding of the relationship between oral-gut microbiome symbiosis and the pathogenesis and progression of non-alcoholic fatty liver disease, as well as discuss novel strategies targeting both P. gingivalis and microbial dysbiosis.
The Research Progress of Exosomes in Osteoarthritis, With Particular Emphasis on the Therapeutic Effect

Exosomes participate in many physiological and pathological processes by regulating cell-to-cell communication. This affects the etiology and development of diseases, such as osteoarthritis (OA). Although exosomes in the OA tissue microenvironment are involved in the progression of OA, exosomes derived from therapeutic cells represent a new therapeutic strategy for OA treatment. Recent studies have shown that exosomes participate in OA treatment by regulating the proliferation, apoptosis, inflammation, and extracellular matrix synthesis of chondrocytes. However, studies in this field are scant. This review summarizes the therapeutic properties of exosomes on chondrocytes in OA and their underlying molecular mechanisms. We also discuss the challenges and prospects of exosome-based OA treatment.
Discrete Cutaneous Feedback for Reducing Dimensions of Wearable Haptic Devices

In this article, we explore alternative cutaneous haptic feedback for rendering modulation of the grasping force. The aim of the study was to reduce power requirements and in turn dimensions of the actuators, in wearable devices applied to virtual or teleoperated manipulation. This is critical in certain rehabilitation or training scenarios where haptics should not interfere with dexterity of the user. In the study, we experimented discrete, pulsed cutaneous force feedback and compared it with conventional continuous proportional feedback, in a virtual pick and place task. We made use of wearable thimbles based on voice coil actuators in order to provide high-quality, low-noise haptic feedback to the participants. The evaluation was performed on the basis of both objective measurements of task performance (measured virtual forces and correct ratio) and a questionnaire evaluating participants’ preferences for the different feedback conditions. On the basis of the obtained results, in the article, we discuss the possibility of providing high-frequency, discretized cutaneous feedback only, driven by modulation of the grasping force. The opportunity is to reduce volume and mass of the actuators and also to consider alternative design solutions, due to the different requirements in terms of static and high-frequency components of the output force.
Lisinopril Mitigates Radiation-Induced Mitochondrial Defects in Rat Heart and Blood Cells

The genetic bases and disparate responses to radiotherapy are poorly understood, especially for cardiotoxicity resulting from treatment of thoracic tumors. Preclinical animal models such as the Dahl salt-sensitive (SS) rat can serve as a surrogate model for salt-sensitive low renin hypertension, common to African Americans, where aldosterone contributes to hypertension-related alterations of peripheral vascular and renal vascular function. Brown Norway (BN) rats, in comparison, are a normotensive control group, while consomic SSBN6 with substitution of rat chromosome 6 (homologous to human chromosome 14) on an SS background manifests cardioprotection and mitochondrial preservation to SS rats after injury. In this study, 2 groups from each of the 3 rat strains had their hearts irradiated (8 Gy X 5 fractions). One irradiated group was treated with the ACE-inhibitor lisinopril, and a separate group in each strain served as nonirradiated controls. Radiation reduced cardiac end diastolic volume by 9-11% and increased thickness of the interventricular septum (11-16%) and left ventricular posterior wall (14-15%) in all 3 strains (5-10 rats/group) after 120 days. Lisinopril mitigated the increase in posterior wall thickness. Mitochondrial function was measured by the Seahorse Cell Mitochondrial Stress test in peripheral blood mononuclear cells (PBMC) at 90 days. Radiation did not alter mitochondrial respiration in PBMC from BN or SSBN6. However, maximal mitochondrial respiration and spare capacity were reduced by radiation in PBMC from SS rats (p=0.016 and 0.002 respectively, 9-10 rats/group) and this effect was mitigated by lisinopril (p=0.04 and 0.023 respectively, 9-10 rats/group). Taken together, these results indicate injury to the heart by radiation in all 3 strains of rats, although the SS rats had greater susceptibility for mitochondrial dysfunction. Lisinopril mitigated injury independent of genetic background.
Species Diversity Regulates Ecological Strategy Spectra of Forest Vegetation Across Different Climatic Zones

Ecological strategy is the tactics employed by species in adapting to abiotic and biotic conditions. The ecological strategy spectrum is defined as the relative proportion of species in different ecological strategy types within a community. Determinants of ecological strategy spectrum of plant community explored by most previous studies are about abiotic factors. Yet, the roles of biotic factors in driving variations of ecological strategy spectra of forest communities across different geographic regions remains unknown. In this study, we established 200 0.04-ha forest dynamics plots (FDPs) and measured three-leaf functional traits of tree and shrub species in four forest vegetation types across four climatic zones. Based on Grime’s competitor, stress-tolerator, ruderal (CSR) triangular framework, and the StrateFy method, we categorized species into four ecological strategy groups (i.e., C-, S-, Int-, and R-groups) and related the ecological spectra of the forests to three species diversity indices [i.e., species richness, Shannon-Wiener index, and stem density (stem abundance)]. Linear regression, redundancy analysis, and variance partition analysis were utilized for assessing the roles of species diversity in regulating ecological strategy spectra of forest communities across different climatic zones. We found that the proportion of species in the C- and Int-groups increased, while the proportion of species in the S-group decreased, with the increase of three indices of species diversity. Among the three species diversity indices, stem abundance played the most important role in driving variations in ecological strategy spectra of forests across different climatic zones. Our finding highlights the necessity of accounting for biotic factors, especially stem abundance, in modeling or predicting the geographical distributions of plant species with varied ecological adaptation strategies to future environmental changes.