Cooperative roles of the suprachiasmatic nucleus central clock and the adrenal clock in controlling circadian glucocorticoid rhythm

The mammalian circadian timing system consists of the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and subsidiary peripheral clocks in other tissues. Glucocorticoids (GCs) are adrenal steroid hormones with widespread physiological effects that undergo daily oscillations. We previously demonstrated that the adrenal peripheral clock plays a pivotal role in circadian GC rhythm by driving cyclic GC biosynthesis. Here, we show that the daily rhythm in circulating GC levels is controlled by bimodal actions of central and adrenal clockwork. When mice were subjected to daytime restricted feeding to uncouple central and peripheral rhythms, adrenal GC contents and steroidogenic acute regulatory protein expression peaked around zeitgeber time 00 (ZT00), consistent with shifted adrenal clock gene expression. However, restricted feeding produced two distinct peaks in plasma GC levels: one related to adrenal GC content and the other around ZT12, which required an intact SCN. Light pulse-evoked activation of the SCN increased circulating GC levels in both wild-type and adrenal clock-disrupted mutant mice without marked induction of GC biosynthesis. In conclusion, we demonstrate that adrenal clock-dependent steroidogenesis and a SCN-driven central mechanism regulating GC release cooperate to produce daily circulatory GC rhythm. © The Author(s) 2017.1

Extent of linkage disequilibrium and effective population size of Korean Yorkshire swine

Objective We aimed to characterize linkage disequilibrium (LD) and effective population size (Ne) in a Korean Yorkshire population using genomic data from thousands of individuals. Methods We genotyped 2,470 Yorkshire individuals from four major Grand-Grand-Parent farms in Korea using the Illumina PorcineSNP60 version2 BeadChip, which covers >61,565 single nucleotide polymorphisms (SNPs) located across all chromosomes and mitochondria. We estimated the expected LD and inferred current Ne as well as ancestral Ne. Results We identified 61,565 SNP from autosomes, mitochondria, and sex chromosomes and characterized the LD of the Yorkshire population, which was relatively high between closely linked markers (>0.55 at 50 kb) and declined with increasing genetic distance. The current Ne of this Korean Yorkshire population was 122.87 (106.90; 138.84), while the historical Ne of Yorkshire pigs suggests that the ancestor Ne has decreased by 99.6% over the last 10,000 generations. Conclusion To maintain genetic diversity of a domesticated animal population, we must carefully consider appropriate breed management methods to avoid inbreeding. Although attenuated selection can affect short-term genetic gain, it is essential for maintaining the long-term genetic variability of the Korean Yorkshire population. Continuous and long-term monitoring would also be needed to maintain the pig population to avoid an unintended reduction of Ne. The best way to preserve a sustainable population is to maintain a sufficient Ne

Anticancer Effect of Nemopilema nomurai

Various kinds of animal venoms and their components have been widely studied for potential therapeutic applications. This study evaluated whether Nemopilema nomurai jellyfish venom (NnV) has anticancer activity. NnV strongly induced cytotoxicity of HepG2 cells through apoptotic cell death, as demonstrated by alterations of chromatic morphology, activation of procaspase-3, and an increase in the Bax/Bcl-2 ratio. Furthermore, NnV inhibited the phosphorylation of PI3K, PDK1, Akt, mTOR, p70S6K, and 4EBP1, whereas it enhanced the expression of p-PTEN. Interestingly, NnV also inactivated the negative feedback loops associated with Akt activation, as demonstrated by downregulation of Akt at Ser473 and mTOR at Ser2481. The anticancer effect of NnV was significant in a HepG2 xenograft mouse model, with no obvious toxicity. HepG2 cell death by NnV was inhibited by tetracycline, metalloprotease inhibitor, suggesting that metalloprotease component in NnV is closely related to the anticancer effects. This study demonstrates, for the first time, that NnV exerts highly selective cytotoxicity in HepG2 cells via dual inhibition of the Akt and mTOR signaling pathways, but not in normal cells

Development and Validation of a Virtual Reality-Based Training Program for Promoting Subjective Well-Being

Objective Enhancing subjective well-being is an effective way to improve mental health. This study aimed to validate a virtual realitybased interactive feedback program as an intervention tool for promoting subjective well-being. Methods Thirty-six males participated in this program, consisting of three tasks constructed based on the theories of positive psychology: 'Experience-based problem recognition task', 'Future self-based success story expression task', and 'Strength expression task'. Participants rated visual analog scores associated with each of the tasks contents. The concurrent validity of task scores was evaluated by correlations with the psychological scale scores. Results The total task score was positively correlated with scores of Mental Health Continuum-Short Form (MHC-SF) emotional wellbeing and psychological well-being, Rosenberg's Self-Esteem Scale, Dispositional Hope Scale agency dimension and pathways dimension, and Life Orientation Test Revised, but not with MHC-SF social well-being scores. After controlling for the effects of the other task scores, the task scores had linear relationships with certain psychological assessments. Conclusion Since the task scores are closely related to indicators of well-being, self-esteem, hope, and optimism, the program contents are well associated with certain aspects of subjective well-being and thus may be available for training that improves subjective well-being through interactive feedback.11Nsciessciscopuskc

Scale-up study for ex-vivo expansion of allogeneic natural killer cells in stirred-tank bioreactor

Natural killer (NK) cells are a type of lymphocyte in the blood that are responsible for innate and adaptive immune response, and they mature in the liver and bone marrow. Being a key role in host defense system with direct and indirect killing of virus-infected cells or cancer cells, NK cell has been considered an attractive candidate for cancer therapy. Peripheral blood shows the low frequency of NK cells, so ex vivo expansion method is important to obtain sufficient NK cells for therapeutic use. Currently, we successfully developed bioreactor process for NK cell expansion on lab-scale. Stirred-tank bioreactor could be considered as optimal alternative system for large-scale NK cell expansion compared with other ones because it is automated, less labor intensive, scalable, well-controlled and cost-effective. In bioreactor process, agitation is one of important parameters for NK cell expansion because it is necessary to provide homogenous culture conditions. So we defined effects of agitation in bioreactor and figured out an optimum condition. After that scale-up studies were carried out with manufacturing-scale bioreactor based on these results. The results in terms of growth rate, viability cytotoxicity and purity, were comparable with lab-scale

Full-endoscopic Foraminotomy in Degenerative Spondylolisthesis: A “Module-based” Approach for Surgical Planning and Execution

Objective Degenerative Lumbar Spondylolisthesis (DSL) is a common spinal pathology characterized by the anterior slippage of one vertebral body on another. DSL is caused mainly by degeneration of the intervertebral disc in the first place, with subsequent degeneration of the facet joints that end causing the slippage. As the disease evolves, stability is restored as a result of advanced degeneration and disc collapse. But while this natural evolution takes place, DSL may produce radicular symptoms by different mechanisms. To present a “module-based” approach for the surgical planning and execution of full-endoscopic foraminotomy in DSL, combined with case examples of the most common surgical scenarios. Methods We propose a “module-based surgery” using the standard endoscopic foraminotomy technique as a baseline. According to the patient’s clinical and imaging characteristics, several “modules” can be added. The resulting endoscopic surgery is a summation of the basic endoscopic foraminotomy plus all the additional required modules. Results Surgical modules description and case examples are provided. Conclusion Transforaminal lumbar endoscopic foraminotomy represents a minimally invasive technique to treat foraminal and combined foraminal-lateral recess stenosis. DSL and its multiple scenarios represent a challenge to the endoscopic surgeon. Module-based approach can help systematize and execute these demanding endoscopic procedures

Methodological Considerations of Electron Spin Resonance Spin Trapping Techniques for Measuring Reactive Oxygen Species generated from metal oxide nanomaterials

Qualitative and quantitative analyses of reactive oxygen species (ROS) generated on the surfaces of nanomaterials are important for understanding their toxicity and toxic mechanisms, which are in turn beneficial for manufacturing more biocompatible nanomaterials in many industrial fields. Electron spin resonance (ESR) is a useful tool for detecting ROS formation. However, using this technique without first considering the physicochemical properties of nanomaterials and proper conditions of the spin trapping agent (such as incubation time) may lead to misinterpretation of the resulting data. In this report, we suggest methodological considerations for ESR as pertains to magnetism, sample preparation and proper incubation time with spin trapping agents. Based on our results, each spin trapping agent should be given the proper incubation time. For nanomaterials having magnetic properties, it is useful to remove these nanomaterials via centrifugation after reacting with spin trapping agents. Sonication for the purpose of sample dispersion and sample light exposure should be controlled during ESR in order to enhance the obtained ROS signal. This report will allow researchers to better design ESR spin trapping applications involving nanomaterials