Alteration of mitochondrial DNA sequence and copy number in nasal polyp tissue

This study was designed to investigate the possibility that mtDNA mutations might arise in inflammatory or chronically damaged nasal polyp tissue from 23 patients. Thirteen patients (57%) displayed nasal polyp tissue-specific mtDNA mutations in the hypervariable segment of the control region and cytochrome b gene, which were not found in the corresponding blood cells and/or adjacent normal tissue. Nasal polyp tissue-specific length heteroplasmic mutations were also detected in nucleotide position (np) 303–315 homopolymeric poly C track (39%), np 514–523 CA repeats (17%) and np 16184–16193 poly C track (30%). The average mtDNA copy number was about three times higher in nasal polyp tissue than in the corresponding peripheral blood cells and adjacent non-polyp tissues. The level of reactive oxygen species (ROS) was significantly higher in the nasal polyp tissues compared to those from the corresponding samples. High level of ROS in nasal polyp tissue may contribute to development of mtDNA mutations, which may play a crucial role in the vicious cycle of pathophysiology of nasal polyps.     

Characterization of Molecular Determinants of the Conformational Stability of Macrophage Migration Inhibitory Factor: Leucine 46 Hydrophobic Pocket

Macrophage Migration Inhibitory Factor (MIF) is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF’s trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G), alanine (L46A) and phenylalanine (L46F), and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.     

Biofortification of crops for reducing malnutrition

Micronutrient deficiencies affect approximately 3 billion people worldwide. Malnutrition hinders the development of human potential and social and economic development in developing countries. The World Health Organization (WHO) and the Consultative Group on International Agricultural Research (CGIAR) have made fighting micronutrient deficiencies, known as hidden hunger, a high priority. Deficiencies of the micronutrients, such as iron, zinc, and vitamin A, are the most devastating among the world’s poor. WHO emphasizes nutrient supplementation and food fortification to address the malnutrition. CGIAR has placed a greater emphasis on biofortification through the HarvestPlus challenge program, and improved micronutrient content of the staple crops (rice, wheat, maize, beans, cassava, pearl millet, and sweet potato) through breeding and biotechnological approaches. An excellent example of biotechnology application is the development of ‘golden rice’ with adequate levels of a provitamin A, β-carotene. The Africa Harvest and the BioCassava Plus programs, respectively, are developing sorghum and cassava with improved nutritional quality. Here, we summarize current strategies of crop biofortification and future prospects towards the development of biofortified crops.     

Preventative Effect of an Herbal Preparation (HemoHIM) on Development of Airway Inflammation in Mice via Modulation of Th1/2 Cells Differentiation

HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4⁺ T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4⁺ T cells displayed increased Th1 (IFN-γ⁺ cell) as well as decreased Th2 (IL-4⁺ cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.     

Animal models of diabetic retinopathy: doors to investigate pathogenesis and potential therapeutics

Effective and validated animal models are valuable to investigate the pathogenesis and potential therapeutics for human diseases. There is much concern for diabetic retinopathy (DR) in that it affects substantial number of working population all around the world, resulting in visual deterioration and social deprivation. In this review, we discuss animal models of DR based on different species of animals from zebrafish to monkeys and prerequisites for animal models. Despite criticisms on imprudent use of laboratory animals, we hope that animal models of DR will be appropriately utilized to deepen our understanding on the pathogenesis of DR and to support our struggle to find novel therapeutics against catastrophic visual loss from DR.     

High Theta and Low Alpha Powers May Be Indicative of BCI-Illiteracy in Motor Imagery

In most brain computer interface (BCI) systems, some target users have significant difficulty in using BCI systems. Such target users are called ‘BCI-illiterate’. This phenomenon has been poorly investigated, and a clear understanding of the BCI-illiteracy mechanism or a solution to this problem has not been reported to date. In this study, we sought to demonstrate the neurophysiological differences between two groups (literate, illiterate) with a total of 52 subjects. We investigated recordings under non-task related state (NTS) which is collected during subject is relaxed with eyes open. We found that high theta and low alpha waves were noticeable in the BCI-illiterate relative to the BCI-literate people. Furthermore, these high theta and low alpha wave patterns were preserved across different mental states, such as NTS, resting before motor imagery (MI), and MI states, even though the spatial distribution of both BCI-illiterate and BCI-literate groups did not differ. From these findings, an effective strategy for pre-screening subjects for BCI illiteracy has been determined, and a performance factor that reflects potential user performance has been proposed using a simple combination of band powers. Our proposed performance factor gave an r = 0.59 (r² = 0.34) in a correlation analysis with BCI performance and yielded as much as r = 0.70 (r² = 0.50) when seven outliers were rejected during the evaluation of whole data (N = 61), including BCI competition datasets (N = 9). These findings may be directly applicable to online BCI systems.     

Recording of elapsed time and temporal information about biological events using Cas9

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